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2000-2001Annual Report

The Royal DanishSchool of Pharmacy

The Royal Danish School of Pharmacy

Annual Report 2000-2001

ISSN 0905-3913

Editor: Jesper Munck (The Royal Danish School of Pharmacy)

Graphic design / AD: Mads Frederik

Print: Centraltrykkeriet Skive

Photos: Mikal Schlosser, Jesper Munck a.o.

The Royal Danish School of Pharmacy

Universitetsparken 2

DK-2100 Copenhagen

Phone: +45 35 30 60 00

Fax: +45 35 30 60 01

E-mail: [email protected]

Internet: www.dfh.dk

ANNUAL REPORT 2000–2001

PAGE 2

Contents


PAGE 3

PAGE

STRENGTHENING OUR ACADEMIC PLATFORM FOR TOMORROW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

IN RETROSPECT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

THE STUDY BOARD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14

PHAMACOTHERAPY – A NEW SUBJECT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16

MANAGEMENT AND ORGANISATION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18

FINANCIAL STATEMENT 2001 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20

STUDENTS. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22

RESEARCH CENTRES AT THE ROYAL DANISH SCHOOL OF PHARMACY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26

PHD DEGREE PROGRAMME . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28

SPECIALISATION IN COMMUNITY PHARMACY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34

THE DEPARTMENTS

DEPARTMENT OF ANALYTICAL AND PHARMACEUTICAL CHEMISTRY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38

DEPARTMENT OF MEDICINAL CHEMISTRY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50

DEPARTMENT OF PHARMACEUTICS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68

DEPARTMENT OF PHARMACOLOGY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82

DEPARTMENT OF SOCIAL PHARMACY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94

THE DANISH PHARMACEUTICAL LIBRARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 104

PUBLICATIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 108

MASTER’S THESES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120

STAFF . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126

The Royal Danish School of Pharmacy:

Strengthening our academic platform for tomorrow

The Royal Danish School of Pharmacy has signed a perfor-

mance contract with the Ministry of Science, Technology and

Innovation under which we agree to implement various teach-

ing and research initiatives. A contract like this places every-

one at the School of Pharmacy, staff as well as students, un-

der an obligation to contribute continuously to our academic

development. The contract also requires management to de-

velop our human resources policy to keep the School in the


Professor, Dsc

(pharm) Povl

Krogsgaard-Larsen

– rector of The

Royal Danish

School of

Pharmacy

PAGE 4

forefront and provide challenges and interesting work for

everyone involved. Everyone is a player in and contributor to

this complex and multifaceted process.

The performance contract provides a framework and objec-

tives for the School. However, at the same time we must

recognise that the School is on its way into a new academic

era. Our working sphere, the field of pharmaceutical sciences

is undergoing rapid change. Major transformations in this

wide academic field, are coupled with the dramatic biomedi-

cal developments of the post-genomic period we now live in.

As the only Danish pharmaceutical institution with research-

based teaching, the School is at the hub of this accelerating

process, which poses major structural and functional chal-

lenges. Although the new situation has enormous potential for

the School, the prerequisite for realising these prospects is

that we show the will and the strength to be effective players

with external partners whose support is absolutely essential

to the process of change.

Many more pharmacists needed

The powerful reinforcement of the fields of biology and bio-

medicine has resulted in a formidable expansion of the basic

knowledge of medical science. The pharmaceutical disci-

plines often set the effeciency in the transformation of medical

knowledge into new drugs and therapies. This factor has al-

ready created bottlenecks, particularly in the pharmaceutical

industry, while the School is under pressure in terms of re-

sources and recruitment. The forecast is that the need for

pharmacists with MSc and PhD degrees in clinical pharmacy

will grow dramatically in the years ahead. In addition we face

mounting pressure from the pharmacy sector to meet their

urgent need for pharmacists. In response we must make

every effort to mobilise resources so that the School’s re-

search capacity as well as MSc and PhD programmes can be

exploited to the full. In the longer term, we must expand the

School’s combined education and research capacity to match

the rapid development of the research-based pharmaceutical

industry and biotechnology sector. The School’s goal must be

to live up to expectations to educate a sufficient number of

key pharmaceutical experts at the MSc and PhD levels in all

relevant branches of the pharmaceutical sphere.

Unrealistic to educate pharmacists at other sites

In order to increase the number of pharmacy graduates, it

has been suggested to establish a pharmaceutical faculty at

the University of Aarhus or University of Southern Denmark in

Odense. The idea has merit on several grounds, as another

institution to provide pharmaceutical education and research

would be desirable, if implementation of a full programme

were possible. However, such an initiative must be consid-

ered unrealistic, at any rate within the next decade or so. We

simply do not have the teaching capacity, and the current dif-

ficulty in recruiting new students to the field presents a seri-

ous obstacle to initiatives of this kind. It is highly improbable

that the universities in either Aarhus or Odense have envi-

sioned establishing a new full-scale pharmaceutical depart-

ment. The idea probably is to add biology masters’ pro-

grammes to their existing chemistry programmes in order to

offer degrees targeted specifically at the pharmaceutical in-

dustry. However, establishing special sector-oriented pharma-

ceutical studies would create problems. The most obvious

solution to the capacity problem would be to expand the

School’s educational capacity by 25-30%. An expansion of

such magnitude would require additional teaching facilities,

new buildings to some extent, and the infusion of the requi-

site financial resources. We have a compelling need to make

THE RECTORS REPORT

The current difficulty in recruiting new students makes the idea of establishing additional pharma-

ceutical faculties unrealistic.

PAGE 5

detailed plans along these guidelines, and to develop a new

educational structure that will stimulate a dynamic interplay

between pharmacy degree programmes and other university

programmes.

The structure and academic profile

of The Royal Danish School of Pharmacy

The future structure and academic profile of the School has

been the subject of extensive debate over the summer and

autumn. Staff and students have been involved in the debate

in a hectic round of meetings. The extent to which the School’s

departmental structure is the best framework for dynamic

educational and research development was questioned. This

issue is central considering the weight that the School attach-

es to disciplinary integration. In addition, however, the discus-

sion on structure also had the important function of fuelling

debate on the School’s academic development in terms of

teaching and research.

This discussion has been promising and constructive, ini-

tially pinpointing some disciplines that warrant special atten-

tion. The decision was made to continue the process of

defining special focus areas that will be dealt with effectively

by working groups with the aim of finding optimal solutions

for integrating disciplines at Master’s level. Initial focus will be

on the area comprising social pharmacy, clinical pharmacy,

pharmacotherapy and pharmacology. These key disciplines

have wide potential, not only in relation to the clinical area but

also very much in connection with the pharmacy sector.

Teaching in physical chemistry is another area of focus.

Physical chemistry is increasingly a vital component in almost

all branches of pharmacy and thus a subject that involves

teachers and students from all departments. Other disciplines

are on the drawing board and will be made into focus areas

in future.

Key role for the Study Board

Naturally, the Study Board holds a key position in discussions

about the academic development of the School. The Study

Board had already started a wide variety of initiatives, such as

revising Degree Regulations and introducing several new

courses. One new initiative I would like to mention in particu-

lar is a compulsory course in the theory of science. Many

hours were devoted to drawing up a new ministerial order for

the master’s degree in pharmacy and for introducing ICT-

based teaching.

The work on the focus areas mentioned above will largely

fall to the Study Board, but will be accomplished by the man-

agement of the School of Pharmacy. In light of the diversity of

the Study Board’s tasks, an ongoing assessment will be

made of the extent to which they could be handled by the

Programme Administration. Insofar as implementation of new

and changed programme modules will imply changes in the

departmental structure of the School, the Senate

(Konsistorium) will naturally be involved in decision-making.

Closing down centres

In terms of research, the year under review was affected by

the political decision to close down the two inter-institutional

centres under the School, Drug Design and Transport and

NeuroScience PharmaBiotec, at the end of their respective

appropriation periods on 31 October and 31 December 2001.

Other centres of corresponding inter-institutional character

were also closed by political fiat. The two centres under the

auspices of the School were closed despite the very positive

international evaluation of their research results as well as the

development and continuation of close cooperation with the

drug industry generated by their activities. This complemen-

tary cooperation between industrial scientists and scientists

at the School, based on mutual trust, is a strong facet of the

School’s research profile.

In contrast, we are pleased that the Drug Design and

Transport Centre has been granted sustenance funds for a

four-year period corresponding to about 25% of the centre’s

appropriation. Only two other centres that were closed down

at other institutions were allocated sustenance funds on a

similar level. Thus we find it positive that the precedent has

been set for continuing and further developing the research

training activities developed in cooperation with the drug in-

dustry within the framework of the two centres under the

School.

Good research development

Research continues to develop well at the School, with the

group of younger scientists increasingly mastering and man-

aging its course. In 2001 many junior as well as senior scien-

tists attracted research funds from external sources. These

research resources have major impact on all academic devel-

opment at the School as well as for the international status of

the individual scientist. It is not possible to list all of those

who have helped put the School on the international research

map. However, special mention must be made of Professor

Mikael Begtrup, who received the prestigious Chemistry

Award from the Carlsberg Foundation, and Anders Asbjørn

Jensen, assistant research professor, who was awarded the

PhD Prize by the Danish Academy of Natural Sciences. Finally

I would like to mention Dung Ngoc Do, precision instrument

maker and a graduate of the School, who received a distin-

guished bronze medal and well-deserved royal handshake for

his apprenticeship project.

In order to combine and reinforce research at the School

and continue to profile research both nationally and interna-

tionally, the decision has been made to set up a number of

strategic focus areas at the School. This new initiative is ex-

pected to lead to a limited number, perhaps four to six, of


PAGE 6

such areas at the School. The ini-

tiative will strengthen and promote

the integration of strong relevant

research areas, and it is expected

that these strategic focus areas to-

gether with other national and in-

ternational research groups will be

able to attract external research

funding.

Research training programmes

The School gives high priority to

research training. Over the years

the School has graduated a large

number of PhDs, both research

pharmacists and graduates with a

different background. When re-

search centres were set up at the

School in 1997, the Graduate

School of Drug Research was es-

tablished on the basis of an alloca-

tion from the then Research

Academy. In the three years since

then the Graduate School of Drug

Research has been the framework

for numerous scientific arrange-

ments targeted at the PhD pro-

gramme. The Graduate School has

also established a total of 15 PhD

scholarships co-financed by the

School, the Research Academy

and industry. Cooperation on grad-

uate studies intensified relations

between the School and other in-

stitutions tied to the centres and the drug industry. An impor-

tant part of this close cooperation is the role of industrial re-

searchers as co-supervisors for PhD students. In recognition

of this activity Novo Nordisk A/S, represented by Professor

Børge Diderichsen, Director of Corporate Research Affairs,

granted DKK 450,000 to award the Novo Nordisk PhD Plus

Prize in recognition of particularly talented PhD students or

PhD graduates.

It is expected that the School’s highly active role in research

training will be continued within the framework of the Drug

Research Academy, a research training programme targeted

at industry. Expected to be established in early 2002, the

Drug Research Academy is based on co-financing from nine

drug companies, the School and the Council on Research

Training (FUR). The last part of the funding package is ex-

pected to be in place shortly. In close interplay with industry,

the Drug Research Academy will provide the platform for

training 36 PhD students over a period of about six years.

THE RECTORS REPORT

PAGE 7

Margrethe

Vestager, then

Minister of

Education, dis-

played in-depth

knowledge and in-

terest in the School

during individual

meetings with stu-

dents, teachers

and management.

Spotlight on The Royal Danish School of Pharmacy

In the area of research training, the School has also earned

wide recognition from its appointment as a Marie Curie

Training Site, headed by Professor Sven Frøkjær. Winning this

appointment from the European Commission in sharp com-

petition with a number of other applicants will give the School

a distinctive European dimension in research training through

its hosting of a considerable number of European PhD re-

search fellows.

It is gratifying for the School to find its place in the land-

scape of Danish and international education and research.

This attention will encourage everyone at the School to do

their utmost to live up to the recognition. To underpin the sig-

nificance of the School’s role, Margrethe Vestager, then

Minister of Education, visited the School in September and

displayed in-depth knowledge and interest in the School

during individual meetings with students, teachers and man-

agement. It was a memorable day.

September 1st 2000 - January 31st 2001

In retrospect


PAGE 8

September 2000: Two-hundred-and-three eager new phar-

macy students arrived to start their degree programme. Also

new were the 2000 Degree Regulations, which introduction

meant a complete restructuring of the pharmacology curricu-

lum, a new programme module in pharmacotherapy, a theory

of science course and the introduction of a bachelor’s degree

– which provides no professional qualification.

The beginning of the academic year also saw the opening of

the newly renovated student centre Alternativet. At the same

time, plans were presented for the conversion of Vivis Minde,

a facility previously used by the Department of Pharmaceutics

but earmarked for student use after conversion.

The environmental chemists at the Department of Analytical

and Pharmaceutical Chemistry and the Drug Delivery group at

the Department of Pharmaceutics had reason to be pleased.

A grant from the Apotekerfonden enabled the purchase of a

mass spectrometer. ‘We’ve had Volkswagen spectrometers

before, but this is a Rolls-Royce model!’ said Jette Tjørnelund

from the Department of Analytical and Pharmaceutical

Chemistry. The department will use the instrument to look for

drug remains in the environment while the Department of

Pharmaceutics will be investigating drug delivery of model

prodrugs in blood, among other things.

Steen Honoré Hansen, professor, DSc (pharm.) and head of

the Department of Analytical and Pharmaceutical Chemistry,

celebrated 25 years of public service. He has always played

an active role in the life of the School and continues to do so.

Tom Børsen Hansen, PhD student, was awarded first prize

for his work Science, general education and competence and

received DKK 40,000 from Margrethe Vestager, Minister of

Education.

In Plexus, Elise Rinvar, pharmacy student, argued for

greater specialisation within the pharmacy programme "to

better prepare the School to meet competition from new

emerging educations," as she puts it.

Dr Hans Lennernäs, professor, Uppsala University, was ap-

pointed assistant professor at the Department of Pharma-

ceutics. The association with an international figure will

strengthen the department’s pharmacokinetic research.

The month ended on a dramatic note when the area sur-

rounding the School was closed off and special forces called

in to arrest a man seen carrying a sawn-off shotgun in the

DSR student council rooms facing the University campus. Six

officers in bulletproof vests armed with pistols made the dis-

covery that the man was in fact a woman, and the gun was a

plastic replica bought for use at the annual initiation of new

students.

October 2000: Wild, wilder, wildest: revelry – student revelry

– reached such heights that Rector Birthe Jensen started get-

ting requests to ban student parties at the School. "I hope

everyone will do what they can to make sure this never be-

comes necessary," the rector urged, suggesting that the stu-

dents behave as though they were at home. "Then they might

treat the School’s property in the same way."

A survey among new students showed that they expect a

high degree of IT-based teaching. After graduating, 8% ex-

pect to find jobs in a community pharmacy while 63% count

on working in the pharmaceuticals industry. About 72% of

new students are female.

Programme director Else Lemmich was adamant that there

are no plans to specialise pharmacy education. "The pro-

gramme is well attuned to the broad job market where gradu-

ates will find work."

BITS AND PIECES

PAGE 9

In connection with Lægemiddeldagene 2000, pharmaceuti-

cal theme days, Verner Andersen, community pharmacist, (lic.

pharm.), was awarded The Danish Pharmaceutical Society’s

gold medal in recognition of his ‘Special contribution to

Danish pharmacy practice’.

Sven Erik Jørgensen from the Department of Analytical and

Pharmaceutical Chemistry was appointed research professor.

Kristian Strømgaard, assistant research professor at the

Department of Medicinal Chemistry, travelled to Slovenia to

receive the Krka Award 2000. The prize is awarded to

promising young scientists whose PhD work has made a sig-

nificant contribution to chemical and pharmaceutical re-

search. An impressive ceremony was staged for the presenta-

tion, which was transmitted by Slovenian TV.

November 2000: The natural product chemistry group at

the Department of Medicinal Chemistry has attracted new

young talent: Henrik Franzyk, chemical engineer, and Dan

Stærk, MSc and biochemist. Both in their thirties, the two

men will replace pharmacists Else and John Lemmich. "Now

that the pharmacy programme is so incredibly broad, we

have to have specialists to teach the individual subjects.

Pharmacists can’t teach everything as a matter of course.

NMR spectroscopy is one example," Dan Stærk points out.

Pharmacy student Jeppe Voss turned over chairmanship of

the student council, DSR, to Rasmus Engelbrecht.

Jørn Bo Sørensen, civil engineer, took up the appointment

of IT department head. "My first priority will be to get the net-

work functioning properly," he said.

Elections for posts on the collegiate bodies were held. DSR

chairman, Rasmus Engelbrecht, commented on voter turnout:

"Somewhere between an election to the church council and

the American presidential election."

December 2000: On Speech Day, Rector Birthe Jensen

explained that the ‘mass drain’ of pharmacists to the private

sector is the reason for the School’s difficulty in attracting and

retaining staff. "We should have transfer agreements like

sports clubs." On the same occasion, the students’ award for

‘Teacher of the Year’ was presented to Ole Jungersen, asso-

ciate professor, PhD, who at the time had already announced

his intention to retire.

At the request of students, the Department of Social

Pharmacy held a teaching day to discuss the communication

of requirements, objectives and methods for the department’s

teaching, as well as proposals to boost student motivation. "It

was a very inspiring form of evaluation," Jacob Grønne, phar-

macy student and member of the Study Board, concluded af-

terwards.

Povl Krogsgaard-Larsen, professor, DSc (pharm.), raised

the issue of whether the School is ready to meet the chal-

lenges of the pharmacy field in the post-genomic period. His

own response is that as a minimum the School must intro-

duce new academic disciplines and carry out reforms in tradi-

tional areas.

January 2001: The Royal Danish School of Pharmacy and

Pharmakon offered a new Specialisation in Community

Pharmacy programme. Nineteen community pharmacists are

enrolled in the new programme, which should be viewed as

an upgrade and further development of the professional quali-

fications of community pharmacists.

The School’s associate and assistant professors met to dis-

cuss recruitment and the problems of retaining present staff

members. The School’s academic staff pointed out that in-

creasing administrative burdens and vacancies means less

time for research. "We’ve reached the limit of what is accept-

able," was the general opinion.

Bjarke Ebert, one staff member who decided after several

years to leave the School for a job in the pharmaceutical in-

dustry, said the problem was not that staff decide to leave

their positions at the School. "That’s simply a fact of today’s

world. The real problem is the School’s inability to hire quali-

fied people to fill these vacancies when they arise."

Chairman of the PhD committee since 1993, Henning

Gjelstrup Kristensen, professor, DSc (pharm.), presided for

the last time over the proceedings at the annual Research

Day and handed over the reins to Erik Wind Hansen, associ-

ate professor, PhD. Research Day is the day on which the

School’s PhD students present the results of their research.

Jens Dencker Christensen, associate professor, PhD, re-

tired from the position of deputy rector, two years before the

expiry of the term. In consequence, the Senate (Konsistorium)

decided to abandon its former practice of electing a rector

and deputy rector for staggered terms, a decision originally

made to ensure continuity in the management of the School.

After the final deadline for nominations to the post of rector

of the School, it became clear that Povl Krogsgaard-Larsen,

professor, DSc (pharm.) would succeed Birthe Jensen, assis-

tant professor, DSc (pharm.), who has held the position since

1988.

An era of 40 years at the Royal Danish School of Pharmacy

finally came to an end: Alex Mehlsen Sørensen, assistant

professor, DSc (pharm.), retired. Programme director, head of

department and department board member are but a few of

the many offices he held over the years.

February 2001: "We must eliminate the issue of the

School’s future status as an independent institution from the

political agenda by offering dynamic, multi-facetted teaching,

research and research programmes," pronounced Povl

Krogsgaard-Larsen, professor, DSc (pharm.), who had a

couple of months yet to wait before taking up the office of

rector. "And we must market the School far more actively."

It was clear that the School’s two multidisciplinary centres,

NeuroScience PharmaBiotec and the Centre for Drug Design

and Transport, would be closed at the end of the year.

Despite positive evaluations and warm recommendations by

the Research Council, a political decision was made to close

down the centres owing to lack of funding.

Poul Kruse, assistant professor, DSc, and Niels Møller,

community pharmacist, PhD, published the seventh volume

of the work on the history of Danish pharmacies, De Danske

Apotekers Historie. A separate volume on a similar subject,

Apotekervæsenets historie i Danmark, was published. "I’ve

never been able to refer to any comprehensive works on

pharmacy and its many different perspectives. This book has

made that possible!" said Poul Kruse.

A new minisite on the School’s website was launched for

prospective students, who can find out all about the pharma-

cy programme and the main fields of pharmaceutical activity

at www.dfh.dk/farmaceut.

March 2001: Should the School offer educational opportu-

nities for postgraduates in subjects other than pharmacy?

What should a Bachelor’s programme contain? Do the

School’s research scientists have a duty to promote aware-

ness of pharmacists and their role in society? Do the two new

programmes at Århus and Odense pose a threat to the phar-

macy programme? Should the School be renamed The

Pharmaceutical University of Denmark? These were just some

of the compelling topics discussed at the student politics

weekend retreat.

Academic staff are not the only group tackling the problem of

recruiting and retaining personnel. Laboratory technicians face

the same dilemma. They are hoping a new pay agreement will

help attract suitable candidates to fill vacant positions.

Only about 130 people felt it worth their while to attend the

School’s open house event, 30% fewer than the previous

year, when a similar decrease on the year before had also

been noted. "The figures are very discouraging," said Ilse

Fjalland, head of the Study Division.

Mikael Ankersen, MSc, defended his doctoral dissertation

entitled Discovery of Peptidomimetic Growth Hormone

Secretagogoues.

April 2001: For the very last time, colleagues Birthe Jensen,

rector, and Jens Dencker Kristensen, deputy rector, chaired a

Senate meeting in these roles.

After four terms of election, it was time for Birthe Jensen,

assistant professor, DSc, to step down. She made this com-

ment about giving praise: “We’re not very good at showing

our appreciation of each other. I urge everyone to try and

make this a more important part of our everyday lives.” And

about the job of rector: “Challenging and exciting of course –

and occasionally frustrating. But never boring!”

None of the School’s research teams featured on the list of

those under consideration for funds granted by Større Tvær-

gående Forskerggrupper to major multidisciplinary research

teams. "There were no projects with a pharmaceutical objective

among the selected teams. This unfortunately reflects the fact

that pharmaceutical activities are only making a limited impact

on the state-based research system," was the disappointed

comment from Povl Krogsgaard-Larsen, professor, DSc.

For the second time, the School decided to advertise itself.

A full-page ad appeared in the youth magazine Chili, encour-

aging readers to get ‘high’ on pharmacy – a comment on an

article a month earlier in the same magazine under the head-

line: Get stoned at the pharmacy – it’s legal.

A survey about the services of the School’s pharmaceutical

library showed general satisfaction among students, whereas

researchers and PhD students did not feel the library met


PAGE 10

their information needs. However, researchers were very sat-

isfied with other aspects of the library service.

May 2001: Bjarne Fjalland, associate professor, PhD, replaced

his title as head of department with that of deputy rector.

At the official reception held to mark Povl Krogsgaard-

Larsen’s appointment as rector, Børge Diderichsen, Director

of Corporate Research Affairs, Novo Nordisk, presented a gift

of DKK 250,000 – to the School’s PhD students.

Villy Dahl Jensen was appointed to head up the School’s

Budgeting and Accounting Division and gave the reassurance

that the School did not appear to be on the verge of

bankruptcy.

June 2001: The Senate (Konsistorium) discussed the pro-

posed departmental structure. With a political question mark

hanging over the future of the School, Povl Krogsgaard-

Larsen, rector, believes it is crucial for the School to signal to

the outside world that it is an institution that moves with the

times. Not all departments, however, are equally enthusiastic

about the new proposals, which include combining some de-

partments. "Explain the advantages of the new structure

first!" students demanded.

The School’s IT action plan was adopted. It proposed inten-

sive efforts in selected focus areas, which have been granted

DKK 500,000 in initial support.

The Teaching Committee assigned Merete Hende, MSc (en-

gineering), the job of mapping the type and extent of IT teach-

ing offered at the Royal Danish School of Pharmacy. The pro-

ject was expected to be completed by the end of the year.

Henning Gjelstrup Kristensen, professor, DSc (pharm.), took

over as chairman of The European Pharmacopoeia, which

contains the quality requirements with which all drugs dis-

tributed in Europe must comply.

July 2001: The Danish Association of Pharmacists, Section

D for pharmacy students, changed its name to Studenter-

netværket [The Student Network]. "We hope the new name

will conjure up an organization with a purpose," explained

board member Jacob Grønne. "And a common purpose and

identity are more important today than ever before," he point-

ed out.

Like all other state institutions, the Royal Danish School of

Pharmacy now has to pay rent for the government-owned

buildings it occupies. The School is therefore granted an ap-

propriation to finance the rent based on the value-added con-

cept, meaning the number of exams passed by students. The

intention is that institutions will economise on space when

they have to pay the cost of using it.

The front cover of the July issue of American Journal of

Physiology, Gastrointestinal and Liver Physiology featured a

picture created by Birger Brodin and Carsten Uhd Nielsen from

the Department of Pharmaceutics using their confocal laser-

scanning microscope. The accompanying article described

new aspects of how peptide transport can be regulated.

August 2001: The School’s new webmaster set himself the

task of making the School’s website more user friendly, dy-

namic and up to date.

Ole J. Bjerrum was made the School’s fourth professor of

pharmacology since the first appointment in the late 1960s. He

comes from a position as research advisor at Novo Nordisk.

At the graduation ceremony, the School noted that the past

academic year had produced 165 graduates, the largest

number ever in the School’s history. Women made up 70%.

After enrolling 194 new students, the School acknowledged

that for the first time it had been unable to fill its admission

quota of 200 places with new pharmacy students.

September 2001: The School was visited by a very well-pre-

pared Margrethe Vestager, Minister of Education. During her visit

she heard about student satisfaction with the programmes and

the School, while academic staff told her about the School’s vul-

nerable position when staff leave for jobs in the pharmaceuticals

industry, and management described the School’s close re-

search ties with industry. "Some people strike the right psycho-

logical chord with me. It’s far easier to help people who enjoy

their work than people who’re forever whining," said the minister

to the enthusiastic representatives of the School.

On the occasion of the publication of the book Eksamen –

eller hvad? [Exams – or what?] Arne Jacobsen, one of its au-

thors, gave examples from the School of how students can

pass an exam without understanding the material. One of his

main points was that the examination form can be an obstacle

to understanding.

The daily media highlighted plans put forward by Sonja

Mikkelsen, Social Democratic member of the Folketing,

Danish parliament, to set up pharmaceutical programmes in

BITS AND PIECES

PAGE 11

Odense and Århus. Both university cities were open to the

proposal.

The Royal Danish School of Pharmacy was appointed a

Marie Curie Training Site. "We are very pleased and proud,"

said Sven Frøkjær, professor, PhD, "because the nomination

is based on the high requirements expected of research insti-

tutions." The Marie Curie Training Sites are part of an EU

framework programme whose objective is to provide financial

support to enable PhD students to complete a study period

at selected research institutions in other EU countries as part

of their education.

The Research Centre for Quality in Medicine Use celebrated

its second birthday. "Although we aren’t a centre in the DKK

50 million class, there’s plenty going on at the centre," as-

sured the centre’s day-to-day manager, Professor Ebba

Holme Hansen.

October 2001: The School’s politically active students

staged a variety of activities aimed at generating greater stu-

dent interest in working on the collegiate bodies. "We need

more students to get involved in discussions and work for a

better School," said Rasmus Engelbrecht, chairman of the

DSR student council.

Surveys held among the School’s new students showed

that the prospect of employment in the public sector does

not hold wide appeal. Not one single student specifically in-

tends to find work in the public sector after graduation. The

outlook is slightly better for community pharmacies, where

7% aim to pursue their career. Top favourite is the pharma-

ceuticals industry, where 65% of the young students hope to

find jobs. At the same time, the survey showed that more

prospective students are using electronic rather than print

media to seek information about pharmacy education and

thus get an idea of the School and what it has to offer.

November 2001: The debate about modifying the depart-

mental structure was put on hold while the discussion about

focus areas in teaching and strategically important research

fields took pride of place. The disciplines of social pharmacy,

clinical pharmacy, pharmacotherapy and pharmacology were

pinpointed initially.

A new initiative teamed the Royal Danish School of Pharmacy

with the Royal Veterinary and Agricultural University to hold an

information day on the natural sciences for careers advisors

from Danish upper secondary schools. "It’s always nice to get

inside information that’s not available anywhere else," one ca-

reers advisor noted in the evaluation questionnaire.

The student body on the Study Board discussed ways of

getting the most out of an in-training period at a pharmacy.

The intention is not to accord lower priority to the profession-

al aspects of a pharmacist’s job but rather to put the time

available to better use.

Pharmacy student Anne Zimmermann replaced Rasmus

Engelbrecht as the DSR student council chairman.

December 2001: DSR’s prestigious teaching prize, Teacher

of the Year, went to Dan Stærk, assistant professor,

Department of Medicinal Chemistry. The DSR jury’s reason:

‘His well-structured, well-prepared approach.’

On Speech Day, Rector Povl Krogsgaard-Larsen said that

the goal of The Royal Danish School of Pharmacy was to meet

the need to produce an adequate number of qualified pharma-

cists at graduate and PhD level. Povl Krogsgaard-Larsen re-

jected the idea of setting up new pharmaceutical programmes

purely to solve the problem of the lack of pharmacists.

Pharmacy student Anne Zimmermann expressed the stu-

dents’ regret at the change of government. "We had just con-

vinced Margrethe Vestager [former Minister of Education] of

the way universities should be run."

Anders A. Jensen, assistant research professor at the

Department of Medicinal Chemistry, received the Danish

Academy of Natural Sciences PhD award for his dissertation

Molecular Pharmacology of Family C G-protein Coupled

Receptors.

Hans P. Merkle, professor of Galenical Pharmacy, Institute

of Pharmaceutical Sciences, Swiss Federal Institute of Tech-

nology Zurich, was appointed assigned professor at the

Department of Pharmaceutics.

The new student building was inaugurated with the antici-

pated festivity.

Mikael Begtrup, professor in organic chemistry, is the first

to receive the newly founded Carlsberg Prize for Research.

His commitment to teaching and maintaining young people’s

interest in chemistry, together with his own great interest in

passing on his knowledge, were some of the factors that led

to the award committee’s nomination of Mikael Begtrup.

The School’s new website was launched.


PAGE 12

The School’s research journal, Lægemiddelforskning, was

published as usual, the only difference being that for the first

time it was issued without the annual report. Instead of fol-

lowing the academic year, it was decided to publish the an-

nual report for a calendar year in keeping with the financial

statement. The change means that the present report covers

the period from 1 September 2000 to 31 December 2001.

BITS AND PIECES

At the beginning of December 2001, the School’s website

underwent changes in both appearance and structure. The

facelift was a direct result of the School’s appointment of a

webmaster. The visual change represents only the first stage

of a longer process intended to expand and optimise the

School’s Internet-related activities and bring them up to date.

Webmaster Henrik Korzen is responsible for the daily run-

ning of the School’s website at www.dfh.dk and Intranet. He

will be ably assisted by Jesper Munck, information officer, as

well as the various departments of the School.

Since his appointment in August 2001, the webmaster’s pri-

mary tasks have included increasing the body of information

on site as well as modernising the layout and making it more

uniform.

December 2001 saw the launch of the new technologically

enhanced site, complete with new structure, new layout and

more information. One particularly welcome feature is the

opportunity to publicise more of the School’s many ongoing

activities.

Other initiatives to improve information levels and introduce

new services in the course of 2002 are already being planned

and prepared. These include electronic teacher-student com-

munication options, better electronic support for students

such as e-learning web pages and discussion fora.

The site structure will be made increasingly dynamic as a

basis for more flexible content and to facilitate the job of

maintaining and updating existing pages. The website will

also be better integrated with the School’s intranet.

One of our aims is to provide easier access to relevant infor-

mation, for instance, by making as much information as pos-

sible available in electronic form for School and external users

alike.

The process is already underway and in the years to come,

the appearance and structure of the School’s website will

gradually be modified in step with the need for an up-to-date

site that continually develops new services.

PAGE 13

New look for the School’s website

The Study Board covering the autumn term of 2000 and all of 2001

The Study Board is responsible for the administration and

development of the curriculum for the Master of Science de-

gree in pharmacy. Within the framework accepted by coun-

tries of the European Union, the Board adapts and develops

pharmaceutical studies to match employment opportunities in

the pharmaceutical sector.

In the period under review, the Study Board has had three

programme directors. Else Lemmich, associate professor at the

Department of Medical Chemistry, was programme director in

autumn 2000, followed by Peter Thygesen, associate profes-

sor, Department of Pharmacology in spring 2001. The under-

signed, Jette Jacobsen, associate professor, has been the pro-

gramme director of the Study Board since autumn 2001.

2000 DEGREE REGULATIONS

The first three terms governed by the 2000 Degree Regulations

were held for the first time in the period under review. Teach-

ing in the other terms in the period was carried out under the

framework of the 1997 Degree Regulations.

Under the 2000 Degree Regulations, the theory of science

module was held in the third term for the first time. The physi-

cal chemistry module was also carried out in a different form

for the first time. The module was previously taught over two

terms, but under the 2000 Degree Regulations is now taught

in its entirety in the third term. The head of the course and

participating students have evaluated the course on theory of

science and the Study Board is awaiting the results. The

Study Board wants related elements of the history of science,

theory of science and scientific methods to be incorporated

into the subjects taught in terms 4-8 under the 2000 Degree

Regulations, and for an elective course on the subject to be

offered as well. These course offerings supplemented by the

teaching already provided in the basic pharmacy course will

ensure a vertical core of teaching in the theory of science.

The Study Board has set up a Course Committee for the the-

ory of science module. The committee will be responsible for

ensuring that the course is held, evaluated and developed.

SUBJECT INTEGRATION

To increase subject integration and coordination between in-

dividual subjects and programme modules as well as to opti-

mise the study plan for the 2000 Degree Regulations and de-

velop the individual subjects, working groups either have

been or are still set up in the following subjects: pharmacog-

nosy, laboratory safety, toxicology, working environment and

statistics. In addition at the request of the Senate at the end

of the period under review, working groups were established

with management participation in physical chemistry and

pharmacotherapy, clinical pharmacy, pharmacology and social

pharmacy. The working group in pharmacognosy concluded

its work at the beginning of 2001 with suggestions for teach-

ing changes and new textbooks, which will be implemented

in the autumn term 2002. The working group in laboratory

safety drew up a compendium on laboratory safety at the

start of the autumn term 2001 for use in all laboratory training

courses in the first three terms. In autumn 2001 the working

group continued working on material concerning biological

safety in the laboratory. This material will be incorporated in

the compendium on safety in the laboratory, so that the com-

bined compendium can be used for all laboratory training

courses offered. The working group in toxicology and working

environment prepared a proposal for a subject description of

working environment. The subject description remains to be

finalised and further work is being done on proposals to coor-

dinate both major and minor elements of toxicology and the

working environment.

WEIGHT ON EVALUATION

In order to ensure the quality and development of the phar-

macy curriculum, the Study Board places great weight on

evaluation. Both single and repeated evaluations are carried

out and finalised in various ways. With regard to the 2000


PAGE 14

Jette Jacobsen, Programme Director, Associate Professor, MSc (pharm.)

Degree Regulations, the Study Board has decided to evaluate

the following: new study modules, study modules subject to

radical changes and study modules that have been allocated

another place in the programme. Up to and including the pe-

riod under review the evaluation was undertaken by the

heads of the courses and participating students either in writ-

ing or orally. During the period under review, the Study Board

drew up a questionnaire for use in subsequent evaluations in

order to standardise the process.

Continuous and systematic evaluations are made at end-of-

term meetings held four times a year. Teachers, student re-

presentatives, heads of department, representatives from the

Study Board and representatives from Student Counselling

attend these meetings. The individual study modules are dis-

cussed in terms of teaching, teaching materials, placement in

the overall programme and coordination with other modules

in the same term.

NEW REQUIREMENTS

After repeated requests from several sides, including stu-

dents, the Senate finally adopted an Information and

Communications Technology (ICT) action plan in 2001.

The Teaching Committee under the Study Board works to

ensure development in teaching methods and to provide a ba-

sis for such development. For example a teaching day is held

every year for all teachers at the School. In the period under

review the topic for the day was ICT in teaching. The commit-

tee has held several mini-meetings for teachers about new

ways to teach and evaluate results. The Teaching Committee

works with the ICT Committee in order to introduce ICT in

teaching in the short term and thus the opportunity to change

the entire evaluation process in the longer term.

In 2001 the Study Board adopted requirements for report-

ing laboratory training in pharmaceutical formulation and pro-

duction, the project in pharmaceutical production, trainee pe-

riods at the pharmacy, alternative traineeships and elective

study modules. The background for the requirement is the

experience of the Study Board that many students apparently

manage to complete large segments of their course of study

– meaning that they carry out most or all of their laboratory

training – without having taken the theoretical part of the

module. When signing up for the study modules listed above,

students must have passed a specified number of obligatory

courses concluded by written examinations. The requirement

has been introduced to raise the level of what students get

out of the teaching and to ensure that the School expends its

resources on students with the right prerequisites.

Every year the Study Board ensures that there is a wide

and interesting selection of elective courses. This provides the

opportunity to quickly establish new courses in order to meet

current preferences both inside and outside the School. The

Study Board approves students’ applications for credit trans-

fer of electives from other institutions of higher education both

in Denmark and aboard. The Study Board registers and draws

up a list of all approved credit transfers so that other students

can consult it for inspiration.

THOUGHTS AND IDEAS WILL BE CONTINUED

At the end of 2001, cooperation with six other institutions of

further or higher education concerning DCN, Dansk Center

for Naturvidenskabsdidaktik (the Danish centre for didactics

and the natural sciences), was concluded, although the

thoughts and ideas behind it will be continued in order to

develop and improve teaching. One of the projects supported

by DCN and entitled "Testing examination forms directed at

understanding" is still ongoing. The aim of the project is to

study whether current teaching, particularly in conjunction

with laboratory training, is sufficiently directed at understand-

ing, as well as to study whether existing examination forms

adequately test the academic understanding of students with-

in pharmacy subjects. If the results are negative, there are

proposals for changes in both teaching and types of exami-

nations.

In 2001 the students on the Study Board initiated a vision-

ary debate that the new Study Board will continue in 2002.

In order to maintain the high number of pharmacy students

who graduate, we must continue to develop curriculum quality.

PAGE 15


The Teaching Committee works with the ICT

Committee in order to introduce ICT in

teaching

Phamacotherapy – a new subject

Professor Helmer Ring Larsen

and Associate Professor Mette Rasmussen

The compulsory course in Pharmacotherapy is a joint venture

between the Department of Pharmacology and the Department

of Pharmaceutics. The course is an innovation as the teach-

ing is practically entirely clinical-problem based. It was intro-

duced in the fall term of 2000.

The aim of the course is to impact knowledge and insight

to the students in etiology, symp-

toms and clinical signs as well as

current therapy in the most im-

portant diseases with respect to

incidence and prevalence. How-

ever, the emphasis is laid upon

the rational use of drugs in gen-

eral and in the particular.

The course consists of introduc-

tory lectures, clinical case presen-

tations and workshops. During

the course the students are pre-

sented with ten clinical cases in

different disease categories in in-

ternal medicine, neurology and

psychiatry. The treatment options

and all aspects of therapy related

to the clinical case presentation is

worked on by the students in

study groups of 3 to 6 during a

one to two weeks period. The

cases are then discussed in a

two hours workshop with active

participation of ca. 50 students at

each session headed by one ex-


PAGE 16

Central vein Hepatic vein

Portal triad

Central vein

Portal vein

Sublobular veinHepatic artery

Portal triads

CLEARANCE

STORAGE

HOMEOSTASIS

SECRETION

METABOLISM

FILTRATIONEXCRETION

SYNTHESIS

Portal triad

Bile duct

ternal and one internal teacher. In the workshop there is ample

time to evaluate the pharmacotherapy and to come up with

suggestions for treatment plans.

The course is finalized by a four hours written examination

consisting of four clinical cases of which the students have to

choose and answer three.

The clinical problembased teaching is executed by 4 inter-

nal teachers and 12 – 16 external lecturers, mainly special-

ized physicians from the Copenhagen University Hospital.

CaseHistory:

The patient is a 57 years old man with a previously heavy al-

cohol consumption and cigarette smoking for many years. He

has developed cirrhosis and chronic obstructive lung disease.

He is admitted because of fatigue, dizziness and tar-coloured

stools for two days. Because of previous bleeding from eso-

phageal varices, ascites and edema he is currently treated

with a non-selective beta-blocker and diuretics. He has been

sleeping during most of the day, while on the other hand he

has had difficulty sleeping at night because of nightmares. He

is complaining of cold fingers and toes as well as headache

and back pain. For his pain he receives paracetamol with

limited effect.

Examination:

On admission the patient is in a poor general and nutritional

condition, conscious but slow cerebrated. He has clinical signs

of cirrhosis, ascites and edema. Arterial blood pressure is

90/60 mm Hg, pulse 52 and temperature 37˚. Following trans-

fusion of four units of blood, the patient appears to be in a sta-

ble condition. Gastroscopy reveals a large ulcer in the duode-

nal bulb, covered with fibrin and without sign of actual bleed-

ing. Only small varices without signs of bleeding may be seen.

PAGE 17

Current treatment:

Tbl. Propranolol retard 160 mg q.d.

Tbl. Furosemide 40 mg b.i.d.

Tbl. Thiamine 300 mg q.d.

Tbl. Paracetamol 1 g t.i.d

Tbl. Ferro-duretter 1 b.i.d.

Lab. Analyses:

hemoglobin 4.1 (8.0 – 11.0 mmol/l). WBC 6.4 (3.0 – 9.0 billion/l), platelets 75 (150

– 400 billions/l), coagulation factors II,VII,X 0.65 (� 0.70), serum-albumin 31 (36.6

84.2 g/l), ALAT 95 (�50 u/l), serum-bilirubin 45 (4 – 22 �mol/l), serum creatinine

0.145 (0.060 – 0.130 mmol/l), serum sodium 128 (136 – 146 mmol/l), serum

potassium 2.5 (3.2 – 4.7 mmol/l), serum ferritin 400 (12 – 300 �mol/l).

Problems to be solved:

1. Explain how you are going to treat the patient’s duodenal

ulcer.

2. Discuss if a biopsy should be taken from this ulcer.

3. Indicate the cause of the tar-coloured stools (melaena).

4. Explain how you are going to optimise the diuretic therapy

and correct electrolytes.

5. Discuss if there is any medication, which ought to be

discontinued.

PHAMACOTHERAPY – A NEW SUBJECT

Management and Organisation

SCHOOL MANAGEMENT

The School is managed in accordance with the Danish

University Law which came into force on 1.1.93. This law

provides a framework within which more detailed regulations

are given by a statute – the present statute being passed in

1994. The School is run by a rector in collaboration with the

Senate (Konsistorium) and Study Board. Assisted by the

deputy rector, the rector is the School’s figurehead and

responsible for day-to-day management. For the period

covered by this report, the rectorate consisted of:

Rector, Professor, DSc (pharm.), Dr honoris causa Povl

Krogsgaard-Larsen

Deputy rector, Associate Professor, PhD (pharm.) Bjarne Fjalland

The rector’s and the deputy rector’s period of office expires 30.4.

2005. The rector and deputy rector are appointed for 4 years.

THE SENATE (KONSISTORIUM)

The Senate is the School’s leading organ. It is responsible for

the School’s interests as an education and research institution

and sets guidelines for long-term activities and development.

Proposals regarding alterations to the School statute have to

be approved first by the Senate and then by the Ministry of

Research. In addition, the Senate has to approve the School

budget. The Senate consists of the rector, who serves as

chairperson, and 14 members, 2 of whom are external and

appointed by Danmarks Forskningsråd (The Danish Research

Council), Forskningsrådenes Formandskollegium (The Chair-

men of the Research Councils) and Uddannelsesrådenes

Formandskollegium (The Chairmen of the Education

Councils).

ON 1. 2. 2002 THE SENATE CONSISTED OF THE FOLLOWING:

Chairperson:

Rector, Professor, DSc (pharm.), Dr honoris causa

Povl Krogsgaard-Larsen

External members:

Vice President, Anders Buur

Pharmacist, PhD (pharm.) Peter Lund Nielsen

Management representatives:

Deputy rector, Associate Professor, PhD (pharm.) Bjarne Fjalland

Head of Study, Associate Professor, PhD (pharm.) Tommy

Nørskov Johansen

Head of Department, Associate Professor, PhD (pharm.) Erik

Wind Hansen

Head of Department, Associate Professor, PhD (pharm.)

Margrethe Rømer Rassing

Head of Department, Professor, PhD. (scient.) Jerzy

Jaroszewski

Scientific staff representatives:

Associate Professor, PhD (pharm.) Bente Gammelgaard

Associate Professor, PhD (pharm.) Lona Christrup

Technical-administrative staff representatives:

Head of Secretariat, MSc (econ.) Henning Bo Nicolajsen

Chief Laboratory technician Ulla Geneser

Student representatives:

Thomas Høgh Jensen

Helle Poulsen

Behzad Ghorbani


PAGE 18

Observers:

Administrator, MA Judith Christiansen

Head of Library Services Alice Nørhede

Head of Department, Associate Professor, MSc (pharm.)

Ebba Holme Hansen

Head of department, Prof., DSc. (pharm.) Steen Honoré Hansen

A series of committees have been established under the

Senate: The Library Committee, Information Committee, PhD

Committee, Stipendium Committee and Election Committee.

THE STUDY BOARD

The Study Board is responsible for the administration and

development of the curriculum for the Master of Science de-

gree in pharmacy. The Study Board consists of 50% scientific

staff and 50% Master of Science students. On 1. 2. 2002, the

Study Board consisted of:

Scientific staff representatives:

Associate Professor, PhD (pharm.) Tommy Nørskov Johansen

(Programme Director)

Associate Professor, PhD (pharm.) Erik Bechgaard

Associate Professor, PhD (pharm.) Ole Jøns

Associate Professor, PhD (pharm.) Søren Troels Christensen

Associate Professor, PhD (pharm.) Uffe Kristiansen

Student representatives:

Tove Kristiansen

Anne Estrup

Behzad Ghorbani

Eva L. Schmidt

Rasmus Engelbrecht

Observers:

Study Manager, MSc (pharm.) Ilse Fjalland.

SCHOOL ORGANISATION

The School’s five departments provide the framework for re-

search, teaching and related activities. Each department is

led by a head of department and a departmental board. The

departments comprise:

The Department of Analytical and Pharmaceutical Chemistry

The Department of Pharmacology

The Department of Pharmaceutics

The Department of Medicinal Chemistry

The Department of Social Pharmacy

A principal co-operation committee and safety committee

have been established for the entire School. Local co-operation

committees have been elected in four of the departments and

in the Administration Department. The School’s Administration

Department is run by the Administrator, whose areas of work

and responsibility are defined by the Rector. The administra-

tion is divided into the secretariat, course administration and

guidance, finance department, higher education administra-

tion system (VUE), IT department, technical services and

building administration.

MANAGEMENT AND ORGANISATION

PAGE 19

RECTORATE

STUDY BOARD

DEPARTMENT OF

ANALYTICAL AND

PHARMACEUTICAL

CHEMISTRY

DEPARTMENT OF

PHARMACOLOGY

DEPARTMENT OF

PHARMACEUTICS

DEPARTMENT OF

MEDICINAL

CHEMISTRY

DEPARTMENT OF

SOCIAL PHARMACY

ADVISORY COMMITTEEPHD COMMITTEE

FIVE DEPARTMENTS LIBRARY

ADMINISTRATION

SAFETY COMMITTEEPRINCIPAL

CO-OPERATION

COMMITTEE

Organisation 2001

SENATE


Financial Statement 2001

The complete 2001 financial statement for The Royal Danish

School of Pharmacy is available in Danish only. For copies

please contact the finance department at The Royal Danish

School of Pharmacy or our website www.dfh.dk

STAFF

The Royal Danish School of Pharmacy employs staff to un-

dertake teaching and research, run the library and handle the

operation of buildings, administration and other tasks. In

2001 the number of full-time scientific staff was 190.6 -sever-

al of whom are PhD students and scientific staff hired on a

temporary basis - a slight reduction compared to 2000, when

the number was 194.3. The reduction is largely due to tem-

porary vacancies in permanent positions.


PAGE 20

Type of scientific staff 2001 (total 201,5 full-time employees).

The scientific staff includes professors, associate professors, assistant professors, PhD students etc.

The part-time staff includes external associate professors, teaching assistants etc.

The technical and administrative staff includes laboratory workers, office workers, technicians etc.

The diagram shows The Royal Danish School of Pharmacy gives high priority to educa-

ting PhD students. The aim is to fulfil the industrial need for good scientists and The

Royal Danish School of Pharmacy’s need for a new generation of scientists to replace

the scientific employees who plan to retire over the next 5-10 years.

Staff employees (full-time)

2000 2001 2002 Budget

Scient. Part-time Technical Total Scient. Part-time Technical Total Scient. Part-time Technical Totalstaff and adm. staff staff staff and adm. staff and adm. staff

staff staff

Teaching 47.7 11.5 79.3 138.5 52.1 10.6 75.6 138.3 52.6 10.1 75.3 138.0

Research 145.6 0.6 37.5 183.7 137.5 0.3 35.3 173.1 148.6 1.0 36.4 186.0

Fundamental (state) 81.1 0.3 13.9 95.3 76.0 0.2 13.3 89.5 81.0 0.5 14.0 95.5

State/priv. Subsidies 53.6 7.6 61.2 51.0 6.6 57.6 54.0 7.0 61.0

PhD education 0.6 0.4 1.0 0.3 0.8 1.1 0.6 0.4 1.0

Contarct work 10.3 0.3 15.6 26.2 10.2 0.1 14.6 24.9 13.0 0.5 15.0 28.5

Library 7.3 7.3 7.7 7.7 8.0 8.0

Buildings 11.4 11.4 8.0 8.0 8.0 8.0

Administration 1.0 17.2 18.2 1.0 18.8 19.8 1.0 18.0 19.0

Others 1.0 1.0 2.3 2.3 3.0 3.0

Other building expenditure 0.0 3.9 3.9 4.0 4.0

Total 194.3 12.1 153.7 360.1 190.6 10.9 151.6 353.1 202.2 11.1 152.7 366.0

FINANCIAL STATEMENT 2001

Total expenditure rose from DKK 178.4 million to DKK 214.3

million, primarily due to the new practice of paying rent for

our buildings. The rental costs of DKK 30.5 million are can-

celled out by rental income of DKK 31.5 million.

Research costs fell by DKK 3.9 million to DKK 85.8 million.

The reduction is in the grant-funded area, which had extraor-

dinarily high expenses in 2000 due to a change in accounting

principles. Thus the reduction in costs does not represent a

reduction in research activities.

Research income derives from several financial sources.

The table ”Revenues for research work” shows that the bulk

of income derives from the state appropriation for basic re-

search. Research revenues have risen from DKK 82.6 million

to DKK 98.0 million, or an increase of DKK 15.4 million. Again

the increase is tied to the change in accounting principles

adopted in 2000, which resulted in extraordinarily low rev-

enues for that year. The increase in the basic government ap-

F INACIAL STATEMENT

PAGE 21

Expenditure (DKK million)

2000 2001

Education 50.106 51.722

Fundamental research 42.295 44.162

Research activitities funded by state and private subsidies 34.585 28.733

Contract research work 0.580 0.907

PhD education 12.268 12.034

Research work total 89.728 85.836

Library 4.512 4.491

Building expenditure 15.574 15.453

Administration 8.755 9.827

Other 1.224 1.501

Common expenses total 25.553 26.781

Tax on real property 2.528 33.119

Other building expenditure 2.997 7.085

Other expenditure total 5.525 40.204

Internal expenditure 3.012 5.251

Total expenditure 178.436 214.285

Revenue for research work (DKK million)

2000 2001

State appropriation for fundamental research 48.300 55.700

State subsidies 13.264 19.180

EU + other international foundations 0.266 0.814

Other foundations 14.424 16.584

Contract research revenue 1.207 0.819

PhD education 5.100 4.900

Total revenue for research work 82.561 97.997

Financial result 2001 (DKK million – years price)

2000 2001 2002

Fin. Statement Fin. Statement Budget

Expenditures

Wages and salary 117.2 120.9 132.8

Other expenses 61.2 93.4 80.1

178.4 214.3 212.9

Revenues

The State Budget net 77.2 111.6 83.9

Other revenues 87.7 108.3 129.0

164.9 219.9 212.9

Result -13.5 5.6 0.0

Result ordinary activity 0.9 5.6 0.0

Result external activity -14.4 0.0 0.0

Total -13.5 5.6 0.0

Accumulated surplus in years prices (DKK million – years price)

2000 2001 2002

Fin. Statement Fin. Statement Budget

Transfer from previous years - ordinary 20.5 21.4 27.0

Transfer from previous years - external 14.4 0.0 0.0

34.9 21.4 27.0

Result this year - ordinary 0.9 5.6 0.0

Result this year - external -14.4 0.0 0.0

-13.5 5.6 0.0

Transfer to next year - ordinary 21.4 27.0 27.0

Transfer to next year - external 0.0 0.0 0.0

21.4 27.0 27.0

propriation for research is connected to a multi-year agreement with

the Ministry of Science, Technology and Innovation, as well as the

incorporation of the Royal Danish School of Pharmacy’s ”Centre for

Drug Design and Transport”.

The Royal Danish School of Pharmacy’s financial performance for

2001 is shown in the table ”Financial results 2001”. An operating

surplus of DKK 5.6 million accrues to a total of DKK 27 million to be

transferred and used to implement strategic objectives in the years

ahead. However, it has not yet been decided whether we will be al-

lowed to keep it all. Special approval from the Ministry of Finance is

required.

Students

MASTER OF SCIENCE (MSC) STUDIES

Since 1994 the number of students enrolled annually has in-

creased to about 200. Figure 1 shows how many students

were enrolled at the School during the period 1991-2001.

The number indicates how many new students were enrolled

as of 1 October in the year of enrolment. The average age of

students enrolled as of 1 September 2001 was 21.9.

For the first time in many years the School has been unable

to fill its admission quota. Thus as of 1 October 2001 only

186 students were enrolled. The reduction in enrolments is

due to a 35% decline in the number of applicants to pharma-

ceutical studies over the past three years. Thus since spring

2001 the School has significantly heightened its focus on re-

cruitment, including promoting the School’s image to its pri-

mary target group of potential applicants, which is graduates

of upper secondary school interested in chemistry and biology.

The majority of the students are admitted 0-2 years after

graduation. This is seen as highly satisfactory and appropriate

for educations based on the natural sciences.

As a result of the increase in enrolments since 1994, the

School’s total student population has also risen significantly

from 925 students in 1991 to 1102 students in 2001. The

student population is counted on 1 October and figure 2

shows the population for the period 1991-2001.

The School’s production of MSc pharmacy graduates is

shown in figure 3. The production of graduate pharmacists


PAGE 22

Enrrolled Students 1991-2001

(as of 1 October in the year of enrolment)

Student Population 1991-2001

(as of 1 October in the year of enrolment)

Number of MSc graduates 1990/91-2000/01

Fig. 1 Fig. 3

Fig. 2

STUDENTS

Single course students on the MSc-programme 1991/92-2000/01

Merit Students

Year 91/92 92/93 93/94 94/95 95/96 96/97 97/98 98/99 99/00 00/01

Number of students 29 10 19 34 70 106 132 147 140 86

Number of course-places 37 14 22 47 125 159 175 171 172 112

Open Education scheme

Year 91/92 92/93 93/94 94/95 95/96 96/97 97/98 98/99 99/00 00/01

Number of students 33 40 76 48 22 28 23 58 40 31

Number of course-places 39 51 105 82 35 51 43 68 49 42

has increased in step with the increased admission of new

students. In future we expect an average production of 150-

160 MSc graduates annually, corresponding to a completion

rate of 75-80%. This is considered highly satisfactory in com-

parison with other types of university studies. In the academic

year 2000/2001 the School produced 165 graduates, the

largest number of MSc pharmacy graduates in the history of

the School. The pharmaceutical job market desperately

needs MSc and PhD graduates in pharmacy, and thus offers

excellent job prospects for both groups.

The average age of MSc pharmacy graduates in 2000/01

was 26.8, which also indicates that the average study period

continues to be low: 5.9 years. 76 % of graduates earned

their MSc degree in six years or less, which is considered

highly satisfactory.

SINGLE COURSE STUDENTS

The School offers students wishing to take single courses

two enrolment options, either as “merit students” (from other

institutions of higher education), or under the “open education

scheme” with partial user payment. The School has required

partial payment since the autumn term of 1995. The School’s

selection of single courses covers all subjects – both compul-

sory and elective – under the Master of Science in pharmacy

programme.

The table shows the development in number of single

course students enrolled in the period 1991/92 - 2000/01.

The considerable reduction in number of merit students in

2000/2001 relative to previous years is due to a special

agreement with the University of Copenhagen that ran from

1996/1997 to 1999/2000. The special agreement allowed

physical education students from the University to enrol in our

basic course on statistics. If we disregard the effect of the

special agreement, there has been no significant difference in

the number of single course students in recent years.

PAGE 23


About half of the single course students are enrolled in accor-

dance with cooperation agreements with the Faculty of

Science of the University of Copenhagen and the Royal

Veterinary and Agricultural University concerning the two-year

MSc course in environmental chemistry. The other single

course students follow a very wide spectrum of our compul-

sory and elective subjects.

INTERNATIONAL STUDENT EXCHANGE

There are wide variations in European health care systems,

which also differ from the American and Australia systems, for

example. Similarly, pharmacy education also varies from

country to country. Ongoing discussions focus on the oppor-

tunities to promote greater uniformity in education, particularly

within Europe, and we are looking at how pharmacists are

put to use in other countries, and what we can learn from

that. Student exchanges are one of the ways we can con-

tribute to constructive and well-founded discussion on the

subject. The School is an eager participant in debate and

supports student exchange.

One of the areas that reflect the School’s commitment to

student exchange is funding. The School spent a total of DKK

250,000 in financing foreign travel, corresponding to approx.

DKK 10,000 per student. Other sources of foreign travel fi-

nancing are the EU Commission’s Socrates/Erasmus pro-

gramme in the amount of approx. DKK 40,000 and the

Scandinavian Nordplus in the amount of approx. DKK

20,000. These funds are returned if students do not utilise

the exchange agreements.

In 2001 student exchanges took place in the following

parts of the world:

During the exchange the majority of students, both those

studying abroad and visiting students, work on their theses,

which are often based on projects carried out in laboratories.

At present the School offers only one course in English,

International Health Care. We have many enquiries from for-

eign students about taking courses here, but the language

barrier often rules out the opportunity for students to visit for

the purpose of taking classes. Students writing theses, how-

ever, can often manage with English, which is spoken by ad-

visors and most people in the laboratories.

Students whose travel has been subsidised by the School

are required to fill in a questionnaire at the end of their stay

abroad. Without exception, they always highly recommend

foreign study to their fellow students. Any other advice they

might have on the basis of their experiences abroad is

passed on to the international office of the School and thus to

other students. A corresponding questionnaire for students

visiting us is being prepared.

PAGE 24

Country Number of Number ofstudents abroad visiting students

Europe 8 6

USA 7 0

Australia 7 0

Other 2 2

STUDENTS

PAGE 25

Research Centres at The Royal Danish School of Pharmacy

NEUROSCIENCE PHARMABIOTEC CENTRE

The NeuroScience PharmaBiotec Centre comprises three sub-

centres, two of which are coordinated by project managers

from H. Lundbeck A/S and NeuroSearch A/S. The third sub-

centre consists exclusively of academic research groups and

is coordinated by the School of Pharmacy. The Centre is

managed overall by the School of Pharmacy.

The aim of the research projects is to produce results that

the pharmaceutical industry may transform into drug develop-

ment projects. The academic research teams do not, how-

ever, target their efforts towards development projects or

problems specific to the industry. Their aim is high level inter-

national research. Results considered to have special poten-

tial are patented and

subsequently published.

It is increasingly acknow-

ledged that only results

of high scientific caliber

push the boundaries of

modern science and

provide value in this

context. Both academia

and the pharmaceutical

industry are aware that

there is no special bene-

fit in university scientists

setting out to solve spe-

cific developmental pro-

blems.

Research scientists

from academic institu-

tions and the pharmaceutical industry share the job of super-

vising PhD students, most of whom spend an internship

period of varying length in industrial laboratories. The next

generation of research scientists will, as far as possible, be

trained to make a solid contribution to innovative pharmaceu-

tical research in partnership with other academic groups.

Although the Neuroscience PharmaBiotec Centre was posi-

tively evaluated by an international panel of experts the Centre

was terminated by political decision at the end of 2001.

CENTRE FOR DRUG DESIGN AND TRANSPORT

The "Centre for Drug Design and Transport" is an extramural

research centre established in November 1997 as a four-year

programme and therefore terminated in October 2001. The

centre is based on seven Danish research groups and funded

by the Danish Medical Research Council, several Danish

pharmaceutical companies and the participating academic in-

stitutions. Professor Sven Frøkjær is the head of the centre.

The Royal Danish School of Pharmacy was granted additional

funding due to a positive evaluation by international referees. In

theory the additional funds will allow the most promising activities

of the centre to be continued for up to another four-year period.

The overall objective of the "Centre for Drug Design and

Transport" has been to study new principles for the design

and transport of drug substances. The goal is pursued by a

highly integrated collaboration between scientists specialised

in different disciplines related to drug research and develop-

ment. The centre covers the follow areas: organic chemistry,

medicinal chemistry, membrane biophysics, drug delivery

pharmacology and clinical research. The participating part-

ners are The Royal Danish School of Pharmacy, Technical


University of Denmark, PET Centre, Aarhus University

Hospital, Centre for Imaging Diagnostics and Medico-tech-

nique, State University Hospital, Department of Dermatology,

University Hospital, Gentofte, and Alpharma A/S, H.Lundbeck

A/S, Leo Pharmaceutical Products A/S, NeuroSearch A/S,

Novo Nordisk A/S and Nycomed Pharma A/S.

The education and training of pharmaceutical scientists in a

thoroughly interdisciplinary manner is a major activity of the

centre and involves scientists from both academia and industry.

FKL – THE RESEARCH CENTRE FOR

QUALITY IN MEDICINE USE

The Research Centre for Quality in Medicine Use (FKL –

Forskningscenter for Kvalitetssikret Lægemiddelanvendelse)

was established in 1999. The overall objectives of the pro-

jects are to provide scientific evidence to optimise the profes-

sionals’ pharmacotherapy and the population’s medicine use.

Hereby, the research contributes to improved public health

and quality of life as well as improved economy of the individ-

ual and the society.

To achieve the Centre’s objectives, the approach has to be

multidisciplinary, inter-professional and trans-institutional. The

researchers involved in the Centre’s activities represent sever-

al disciplines including clinical pharmacy, epidemiology, gen-

eral practice, health economics, health policy, public health,

social pharmacy and sociology. Groups from the following

academic and public institutions participate in the Centre:

Pharmakon, the Danish College of Pharmacy Practice, the

County of Vestsjælland, the County of Funen, Copenhagen

County, the National Institute of Public Health, Copenhagen

University, the University of South Denmark, Aalborg Univer-

sity, the University Hospitals Centre for Nursing and Care

Research (UCSF), the Institute of Rational Pharmacotherapy

and NEPI – the Swedish Network for Pharmacoepidemiology.

The Centre is managed by the School of Pharmacy and di-

rected by Professor Ebba Holme Hansen of the Department

of Social Pharmacy.

The Centre for Quality in Medicine Use embraces a range of

projects. The major share of the Centre’s resources has been

allocated to projects about pharmacy practice. The Pharmacy-

University Study has broken new grounds by establishing an

action research triangle which unites community pharmacists,

pharmacy students and researchers in an effort to uncover

medicine related problems and information needs of patients

suffering from angina pectoris, asthma and diabetes. Another

pharmacy practice project is focusing on self-care and self-

medication. After piloting, this project has reached the inter-

vention phase.

Another group of Centre studies analyses the Danish popu-

lation’s medicine use through data obtained from question-

naire based surveys of large representative samples of ado-

lescents and adults.

Macroperspectives on medicine supply is a thematic area

looking into e.g. deregulation of the pharmacy sector and the

views of different interested parties. The new medicine con-

sumer is an innovative substudy analysing the users’ per-

spectives in relation to global consumer trends.

Further centre projects deal with the user’s perspective on

medicine use. Under this umbrella a Danish team is coordi-

nating a strong international multidisciplinary research group.

Much interest in Danish health care is devoted to the quality

of physicians’ prescribing.

The FKL-centre carries out qualitative and quantitative

analyses to establish a research foundation for interventions

into GPs’ prescribing.

The 1991 Pharmacy

Foundation has been

the major external

sponsor of the Centre’s

activities, but funding is

also provided by the

Foundation for Finan-

cing Research in Gen-

eral Practice and in the

Health Service (The

Research Foundation),

the Health Insurance

Fund, the Danish Medi-

cal Research Council’s

Regional Fund for

Eastern Denmark and

various private funds.

NEUROSCIENCE PHARMABIOTEC CENTRE

PhD degree programme

The Danish PhD degree is a three-year programme compris-

ing a research project, courses at PhD level, teaching and

communication activities, an independent PhD thesis and

subsequent defence. It is customary for PhD students to inte-

grate a three to six month study visit to a research institute

outside The Royal Danish School of Pharmacy during the

course of the degree programme, preferably abroad.

As of 1 October 2001, a total of 131 students were enrolled

at the school. The distribution by gender was relatively con-

stant in 2000/2001, 1999/2000 and 1998/1999, i.e. 49%

women and 51% men. We find this gender distribution satis-

factory.

The age of PhD students at the time of enrolment varies

slightly. In 2000/2001, the average age at the time of enrol-

ment was 29.2 years; 27.6 years for the PhD students em-

ployed at the School. Among the enrolled PhD students,

pharmacists account for about 60%, chemists and biologists

23% and engineers 8%. About 8% of the PhD students hold

a MSc degree from abroad.

The School provides financial support to 56 of the 131 PhD

students, in part through its own scholarships and in part

through co-financed scholarships. The majority of the PhD

students are fully or partly funded by external co-operators.

There is a great need for PhDs in industry and thus also for

external funding.


Degree 1996/97 1997/98 1998/99 1999/00 2000/01

Pharmacist 67% 66% 64% 56% 60%

Chemist/biologists 15% 15% 22% 24% 23%

Engineers 4% 8% 2% 9% 8%

Abroad 12% 9% 6% 7% 8%

Age when enrolled

Enrolments

Number of PhD students enrolled

PAGE 28

The 131 PhD students are enrolled as follows:

21 (16%) at the Department of Analytical and

Pharmaceutical Chemistry

23 (18%) at the Department of Pharmacology

35 (27%) at the Department of Pharmaceutics

43 (33%) at the Department of Medicinal Chemistry

9 (7%) at the Department of Social Pharmacy.

From 1 October 2000 to 30 September 2001, PhD degrees

were conferred on 29 PhD students. In addition, one person

registered in 2000/2001 for assessment without matriculation.

The students were enrolled for 3 years and 11 months on av-

erage, a decrease compared to 1998/99 and 1999/00. This

development is satisfactory as the enrolment period is count-

ed from the first day of enrolment to the day the PhD degree

is conferred. The average duration of enrolment is affected by

maternity leave, for one, but other unknown factors may con-

tribute as well.

The majority of the PhD graduates from the School are em-

ployed by the pharmaceutical industry, many even before

their PhD degree is conferred.

PHD COURSES

From 1 September 2000 to 31 December 2001 the school

taught 18 courses specifically intended for PhD students.

PHD TRAINING

PhD degrees conferred

Length of enrolment

PAGE 29

Participants were primarily PhD students from the School and

other Danish universities and young scientists from the phar-

maceutical industry. Efforts are made to increase the interna-

tional participation in the PhD courses, as well as the Danish

participation in PhD courses taught by partners in the interna-

tional ULLA collaboration.

ULLA SUMMER SCHOOL

The fifth ULLA Summer School was held in London in August

2001. The summer school is organised every other year by

the ULLA collaboration consisting of the Faculty of Pharmacy

(University of Uppsala), the School of Pharmacy (University

of London), Leiden/Amsterdam Centre for Drug Research

(University of Leiden and Vrije Universiteit Amsterdam), the

Faculty of Pharmacy (University of Paris South), and The

Royal Danish School of Pharmacy.

A total of 124 PhD students and young scientists from in-

dustry participated in the summer school in London, 26 of

them PhD students from the School. Teachers from ULLA in-

stitutions also participated, nine of them from Copenhagen.

The ten-day summer school offered 32 courses, each lasting

from one to two days. Posters by participants were accessi-

ble throughout the Summer School.

A symposium was organised on “Non-Viral Gene Delivery”.

RESEARCH DAY

Every year the PhD Study Board organises a Research Day in

order to give PhD students the opportunity to make an oral

presentation or present a poster about their research project.

Research Day was held on 12 January in 2001. Professor

David Ganderton from the University of Bath was the guest

speaker.

NEW MINISTERIAL ORDER ON THE PHD DEGREE

In 1999 the PhD programme in Denmark was evaluated by

the Danish Research Council. The final evaluation report was

discussed by the PhD Study Board, which found recommen-

dations made in the evaluation well in keeping with the

School’s current policies. The report has given rise to a dis-

cussion about the strategic goals of the pharmaceutical PhD

programme, in particular with regard to the international di-

mension.

In June 2001 the PhD Study Board discussed the draft of a

new ministerial order on the PhD programme and the PhD

degree. We are waiting for the new ministerial order from the

Ministry.

Graduate School of Drug ResearchThe research training school, Graduate School of Drug

Research, was established in September 1998 on the basis

of a 5-year grant from the Danish Research Academy. The

aim of the Graduate School is to train the next generation of

drug researchers. Emphasis is placed on integrated research

training with the aim of performing innovative drug research in

an interdisciplinary and highly integrated research environ-

ment. The industrial perspective of drug research is essential

to the study program. The Graduate School was at the es-

tablishment primarily based on the activities of two research

centres, The NeuroScience Centre (1997-2001) and The

Centre for Drug Design and Transport (1997-2001), although

participation is open to all PhD students who meet the

school's requirements.

From December 1998 to August 2001, The Graduate

School initiated 17 PhD studentships co-financed by the

Royal Danish School of Pharmacy, The Danish Research

Academy and the pharmaceutical industry. The Graduate

School grants financial support to PhD courses at the School

of Pharmacy to ensure the participation of leading internatio-

nal scientists as lecturers.

The Graduate School has been involved in the organization

and hosting of a series of mini-symposia, often in collaboration

with the above-mentioned research centres or scientific asso-

ciations. During the period January-December 2001 the Gra-

duate School of Drug Research organized 7 mini-symposia.

All of these symposium arrangements were widely announced

and were attended not only by PhD students enrolled at the

Graduate School but also by a number of other PhD students

and scientists from both academia and the drug industry. One

of these mini-symposia was organized as a two-day arrange-

ment at Sorø Storkro with Dr. Wolfgang Froestl, Novartis

Pharma AG, Basel as the keynote speaker. All of the mini-

symposia organized at the Royal Danish School of Pharmacy

were also very well attended, and in agreement with the over-

all goal of the Graduate School, these arrangements are in-

creasingly attracting junior scientists from Northern Germany

and from the other Scandinavian countries. This international

interest probably reflects that most of the speakers at the

symposia are international recognized scientists. Titles of the

mini-symposia organized at the Royal Danish School of

Pharmacy were "Applied Heterocyclic Chemistry", "Receptor

Structure and Function", "ADME in Drug Research", "Drug

Design Copenhagen 2001", "Reactive Drug Metabolites -

their formation, reactions, and the toxicological conse-

PHD DEGREES FROM 1 SEPTEMBER 2000

TO 30 SEPTEMBER 2001

Jens Buchardt

PhD Thesis: A Solid Phase Combinatorial Approach

to Phosphinic Peptide Inhibitors of Matrix Metallo-

proteinases.

Supervisors: Associate Professor Per Vedsø,

Department of Medicinal Chemistry, Professor

Morten Meldal, Carlsberg Laboratory and Dr Niels

Tækker Foged, Carlsberg Laboratory

Enrolled at Department of Medicinal Chemistry.

Karin Löwenstein Christensen

PhD Thesis: Design of Redispersible Dry Emulsions.

A Potential Oral Drug Delivery System.

Supervisors: Professor Henning Gjelstrup Kristensen,

Department of Pharmaceutics and PhD Gitte

Pommergaard Pedersen, Leo Pharmaceutical

Products

Enrolled at Department of Pharmaceutics.

Gerda Marie Friedrichsen

PhD Thesis: Peptide-Coupled Compounds Targeted

for the Oligopeptide Transporter. Synthesis and Bio-

logical Evaluation.

Supervisors: Professor Mikael Begtrup, Department

of Medicinal Chemistry, Associate Professor Per

Vedsø, Department of Medicinal Chemistry, Asso-

ciate Professor Bente Steffansen, Department of

Pharmaceutics and MSc Palle Jakobsen, Novo

Nordisk A/S


Patrick Garibay

PhD Thesis: The Combinatorial Synthesis of Possible

Insulin Mimetics.


Department of Medicinal Chemistry, Professor Mikael

Begtrup, Department of Medicinal Chemistry and

Chemist Thomas Høeg-Jensen, Novo Nordisk A/S


Thomas Groth

PhD Thesis: Methodology for Solid Phase Combi-

natorial Synthesis of Novel Peptide Isosteres and

Mimetics Derived from N-Terminal Peptide Aldehydes.


Department of Medicinal Chemisty and Professor

Morten Meldal, Carlsberg Laboratory


Steen Gyldenkærne

PhD Thesis: Risk Assessment of Pesticides in Agri-

cultural Fields with Special Emphasis on Carabids

and Staphylinids.

Supervisors: Associate Professor Sven Erik

Jørgensen, Department of Analytical and Pharma-

ceutical Chemistry, Associate Professor Bent Halling-

Sørensen, Department of Analytical and Pharma-

ceutical Chemistry and Research Manager Jørgen

Jacobsen, The Danish Institute of Agricultural

Sciences

Enrolled at Department of Analytical and

Pharmaceutical Chemistry.


All of the mini-symposia or-

ganized at The Royal Danish

School of Pharmacy were

very well attended.

quences" and "From Receptor to Prescription in Clinical

Neuropsychiatry".

Dr. Sonata Krikstolaityte, Kaunus University, Latvia spent a

6-month period at the Graduate School working on a project

focusing on the conversion of wasp polyamine toxins into

pharmacological tools and potential drugs. During this re-

search stay Professor Algirdas Sackus, Kaunus University,

Latvia visited the Graduate School as a guest scientist a

number of times. Dr Mogens Nielsen was associated with the

Graduate School for a number of months. Mogens Nielsen

played a key role in the organization of one of the PhD cours-

es "In Vivo Neuropharmacology" and was involved in the

planning of the PhD course "Cellular Pharmacology and

PAGE 31

Toxicology". In addition, he organized and carried through a

very well attended study circle on fluorescence technologies

in pharmacological and biomedical research.

A number of internationally recognized scientists visited the

Graduate School as guest lecturers, notably Professor Leo

Hösli, University of Basel and Vice President, Dr Claus

Bræstrup, H. Lundbeck A/S.

Based on two major grants to the Graduate School of Drug

Research from Novo Nordisk A/S, the Graduate School was

in a position to grant 3 PhD's, who had completed very suc-

cessful PhD projects, Novo Nordisk PhD Plus Prizes. One of

the prize recipients also received the PhD Prize of the Danish

Academy of Natural Sciences.

PHD TRAINING

Tina Weinkauf Hahn

PhD Thesis: Acetainophen (paracetamol). – Pharma-

cokinetics and Analgesic Effect in Postoperative

Patients.

Supervisors: Associate Professor Mette Rasmussen,

Department of Pharmaceutics, Associate Professor

Janne Rømsing, Department of Pharmaceutics and

Dr.med. Steen W. Henneberg, Rigshospitalet and

Research scientist Helle Angelo, Bispebjerg Hospital


Birgit Sehested Hansen

PhD Thesis: Characterisation of in vitro Growth

Hormone Release Stimulated by Growth Hormone

Releasing Hormone and Growth Hormone

Secretagougues.

Supervisors: None.

Enrolled at as an independent student.

Henrik Hegnbo Hansen

PhD Thesis: The Impact of Brain Injury: Involvement

of the System of Endocannabinoid Ligands and Re-

ceptors.

Supervisors: Associate Professor Harald S. Hansen,

Department of Pharmacology and Professor Steen

Honoré Hansen, Department of Analytical and Phar-

maceutical Chemistry

Enrolled at Department of Pharmacology.

Anders Asbjørn Jensen

PhD Thesis: Molecular Pharmacology of Family C

G-Protein Coupled Receptors.

Supervisors: Professor Povl Krogsgaard-Larsen,

Department of Medicinal Chemistry, Research

Scientist Hans Bräuner-Osborne, Department of

Medicinal Chemistry and Head of department

Christian Thomsen, H. Lundbeck A/S


Anette Gemal Jensen

PhD Thesis: Quality Assessment of Herbal Re-

medies. Focus on Phytopharmaceuticals Containing

Hypericum perforatum L. and Ginkgo biloba L.

Supervisors: Professor Steen Honoré Hansen,

Department of Analytical and Pharmaceutical Chemi-

stry, Associate Professor Lene Gudiksen, Department

of Medicinal Chemistry, and Head of Department

Elsebet Østergaard Nielsen, NeuroSearch A/S



Mads Skak Jensen

PhD Thesis: Cyanide Toxicology – Insights into

Mechanisms of Action and Antidotal Strategies.

Supervisors: Associate Professor Erling Sonnich

Thomsen, Department of Analytical and

Pharmaceutical Chemistry and

Professor Niels C.B. Nyborg, Novo Nordisk A/S



Simon Bjerregaard Jensen

PhD Thesis: Parenteral Water-in-Oil Emulsions as

Sustained Release Systems for Hydrophilic Com-

pounds.

Supervisor: Professor Sven Frøkjær, Department of

Pharmaceutics, Associate Professor Charlotte

Vermehren, Department of Pharmaceutics and Dr

Ingrid Söderberg, Leeds University


Pia Knudsen

PhD Thesis: The Experience of Younger Women with

SSRI Antidepressants – a User Perspective.

Supervisors: Professor Ebba Holme Hansen,

Department of Social Pharmacy and Associate

Professor Janine Morgall, Department of Social

Pharmacy

Enrolled at Department of Social Pharmacy.

Hasse Kromann

PhD Thesis: Glutamate Receptor Ligands: Synthesis

and Pharmacological Characterization.


Department of Medicinal Chemistry, PhD Frank A.

Sløk, NeuroSearch A/S and Associate Professor

Tommy N. Johansen, Department of Medicinal

Chemistry


Iben Larsson

PhD Thesis: Comminution of Particulate Solids in a

Micros Ring Mill.


Department of Pharmaceutics and Associate Pro-

fessor Jørn Møller-Sonnergaard


Karsten Lindhardt

PhD Thesis: Nasal Drug Delivery.

Supervisors: Associate Professor Erik Bechgaard,

Department of Pharmaceutics, Professor Sveinbjörn

Gizurarson, Iceland University, Head of Department

Hanne Wulff Nielsen, Nycomed Pharma A/S and

Head of Department Erik Didriksen, Leo Pharma-

ceutical Products


Hans-Christian Holten Lützhøft

PhD Thesis: Environmental Risk Assessment of

Antimicrobials.

Supervisors: Associate Professor Sven Erik

Jørgensen, Department of Analytical and Pharma-

ceutical Chemistry and Associate Professor Bent

Halling-Sørensen, Department of Analytical and

Pharmceutical Chemistry



Rasmus Worm Mortensen

PhD Thesis: Reactive Drug Metabolites.

Supervisors: Professor Steen Honoré Hansen,

Department of Analytical and Pharmaceutical Che-

mistry, Associate Professor Jette Tjørnelund, Depart-

ment of Analytical and Pharmaceutical Chemistry,

Associate Professor Claus Cornett, Department of

Analytical and Pharmaceutical Chemistry and PhD

Ulla Grove Sidelmann, Novo Nordisk A/S



Addmore Ndekha

PhD Thesis: Strengthening Community Participation

in Schistosomiasis Control: Lessons from the Guruve

District (Zimbabwe) Schistosomiasis Control Programme

Using Phytolacca Dodecandra (a Plant Molluscicide).

Supervisors: Professor Ebba Holme Hansen,

Department of Social Pharmacy, Dr. Godfrey Woelk,

University of Zimbabwe, Associate Professor Per

Mølgaard, Department of Medicinal Chemistry and

Senior Advisor Peter Furu, Danish Bilharziasis Labo-

ratory Enrolled at Department of Social Pharmacy.

Annette Sams Nielsen

PhD Thesis: Characterisation of CGRP Induced

Effects in Human and Guinea Pig Cerebral Arteris.

Chasing Functional Receptor Heterogeneity.

Supervisors: Associate Professor Inger Jansen-

Olesen, Department of Pharmacology and Professor

Jan Engberg, Department of Pharmacology


Carsten Uhd Nielsen

PhD Thesis: Intestinal Peptide Transporter Mediated

Drug Delivery Using Stabilized Dipeptide Pro-Moities.

Affinity, Transport, Drug Release and Regulation.

Supervisors: Associate Professor Bente Steffansen,

Department of Pharmaceutics, Professor Sven

Frøkjær, Department of Pharmaceutics, Research

Associate Professor Birger Brodin Larsen, Depart-

ment of Pharmaceutics and Chemist Mitchell E.

Taub, Novo Nordisk A/S


PAGE 32

Attentive listeners at the Research Day 2001.


Pernille Bondeskov Nielsen

PhD Thesis: Tocopherol as an Oral Drug Delivery

System.



Anette Müllertz, Department of Pharmaceutics and

Thomas Norling, Dumex-Alpharma


Peter Aadal Nielsen

PhD Thesis: Strongly Polar Molecules in Aqueous

Solution Studied by NMR and Computational

Chemistry.

Supervisors: Professor Tommy Liljefors, Department

of Medicinal Chemistry, Professor Jerzy Jaroszewski,

Department of Medicinal Chemistry, Associate

Professor Per-Ola Norrby, Department of Medicinal

Chemistry and Head of Department Klaus

Gundertofte, H. Lundbeck A/S


Torben Rasmussen

PhD Thesis: Molecular Modeling of Assymetric

Catalysts.

Supervisors: Associate Professor Per-Ola Norrby,

Department of Medicinal Chemistry, and Professor

Mikael Begtrup, Department of Medicinal Chemistry


Anette Graven Sams

PhD Thesis: Solid Phase Aldol and Diels - Alder

Reactions in the Formation of Novel Peptide Isosters

as Putative Protease Inhibitors.


Department of Medicinal Chemistry and Professor

Morten Meldal, Carlsberg Laboratory.


Majid Sheyhkzade

PhD Thesis: Characterisation of Calcitonin Gene-

Related Peptide Receptor Subtypes and Function in

Rat Coronary Arteries.

Supervisors: Professor Niels C. Berg Nyborg, Novo

Nordisk A/S


Ulrik Sidenius

PhD Thesis: Purification and Analysis of

Selenoprotein P from Human Plasma.

Supervisors: Associate Professor Bente

Gammelgaard, Department of Analytical and

Pharmaceutical Chemistry, Associate Professor Ole

Jøns, Department of Analytical and Pharmaceutical

Chemistry and Professor Ole Farver, Department of

Analytical and Pharmceutical Chemisty


Pharmceutical Chemistry.

Gitte Elgaard Terp

PhD Thesis: Molecular Modeling of Matrix Metal-

loproteinases and Their Inhibitors – A New Concept

for Ligand Selection and Prediction of Binding

Affinities.

Supervisors: Associate Professor Flemming Steen

Jørgensen, Department of Medicinal Chemistry and

Chemist Inge Thøger Christensen, Novo Nordisk A/S


Daniel Brunicardi Timmermann

PhD Thesis: Subcellular Localization and Pharma-

cological Characterization of Voltage Gated Calcium

Channels in Cultured Neocortical Neurons.

Supervisors: Professor Arne Schousboe, Department

of Pharmacology, Associate Professor Uffe

Kristiansen, Department of Pharmacology


Marianne Willert

PhD Thesis: A Combinatorial Library Approach to the

Identification of Protease Substrates and Inhibitors.


Department of Medicinal Chemistry and Professor

Morten Meldal, Carlsberg Laboratory


Niels Hønberg Zangenberg

PhD Thesis: A Dynamic in vitro Lipolysis Model.



Anette Müllertz, Department of Pharmaceutics and

Managing Director Lars Hovgaard, Galenica Aps


PHD TRAINING

PAGE 33

Evaluation of the oral presentations at the Research Day 2001. Former PhD study Administrator Eva Horn Møller, the

new Chairman of the PhD Committee Erik Wind Hansen and the former Chairman Henning Gjelstrup Kristensen. Both

Erik Wind Hansen and Henning Gjelstrup Kristensen have been members of the PhD Committee since 1993.

Specialisation inCommunity Pharmacy

Head of the Study Board for Specialisation in Community

Pharmacy, Associate Professor, Poul R. Kruse, DSc (pharm)

The educational scope of The Royal Danish School of Phar-

macy is not restricted to the curriculum for the MSc degree in

Pharmacy and PhD programmes. The School also sees it as

its duty to provide further and continuing education program-

mes for pharmacists, including those working in community

pharmacies. The School has therefore been actively involved

in developing systematic continuing education for community

pharmacists ever since programmes were introduced in 1966.

Similarly, the School is represented on the Advisory Committee

on Pharmaceutical Training, EU, one of whose aims is further

education for community pharmacists. The School is keen to

help promote the use of pharmaceutical knowledge through-

out the health care sector.

Recent years’ recommendations by EU and WHO advisory

committees on pharmaceutical training have prompted dis-

cussions along these lines between the School and profes-

sional authorities and organisations, including Pharmakon a/s,

which runs the established pharmaceutical continuing educa-

tion programme. In this connection, the question of the need

for specialisation in community pharmacy was raised. As a

result of these talks, representatives from the Department of

Social Pharmacy and Pharmakon a/s prepared a proposal for

regulations for a specialised programme that complies with

the recommendations of the EU’s advisory committee. The

professional authorities and organisations expressed their

support for the proposal during subsequent discussions.

It was against this background that the Senate of The Royal

Danish School of Pharmacy decided in April 2000 to intro-

duce a specialised programme in community pharmacy at the

School, in cooperation with Pharmakon a/s and to appoint a

study board for the new programme with representatives from

all sectors of the pharmaceutical profession. In June 2000,

Apotekerfonden af 1991 provided a grant to develop the

specialised programme and establish a secretariat, making it

possible to launch the programme on 1 January 2001.

The specialised programme is intended for community phar-

macists with at least two years’ working experience. Based

on the pharmacist’s professional knowledge and practical ex-

perience, the programme aims to supplement pharmacists’

pharmacological, managerial and personal qualifications. On

completion of the programme, the School issues a certificate

documenting the qualifications gained. The programme is

therefore an opportunity for community pharmacists to devel-

op and gain accreditation for specialist skills acquired through-

out their career, regardless of whether their goal is to be a

pharmacy manager with responsibility for the professional

development of others or a community pharmacist.

The specialised programme in community pharmacy consists

of the following main subjects:

1. Pharmacotherapy and symptom assessment, including

anatomy, physiology, pharmacology, pharmacokinetics,

symptomatology and pathology.

2. Pharmacy practice: Performance and development of the

pharmacy’s professional services based on WHO’s Guidelines

on Good Pharmacy Practice (GPP), including:

• Prescription medications for individuals: distribution, in-

formation to patients and ensuring results (pharmaceuti-

cal care)

PAGE 34


• Personal care and symptom assessment

• Disease prevention and health promotion

• Rational medication consumption.

3. Social pharmacy: Disease-, medication- and health-related

behaviour, healthcare economy, pharmacoepidemiology and

management of medication consumption.

4. Healthcare advice and information, including methods for

advising individuals, informing target groups, and general

instruction.

5. Documentation and information, including quality devel-

opment, evaluation and surveys of pharmacy practice;

use of pharmaceutical information systems and information

technology.

6. Pharmacy operations, including management, skills devel-

opment, organisation, operations and economy.

The specialised programme has a standard duration of one

working year, corresponding to 60 European Credit Transfer

System points (ECTS points). Pharmacists attend the pro-

gramme, which runs over a minimum of two and a maximum

of six years, alongside their regular community pharmacy job.

The programme consists of the following elements:

• Compulsory courses (12 points)

• Elective courses (minimum 12 points)

• Literature study (maximum 5 points)

• Study trip (maximum 5 points)

• Dissertation (minimum 15 points).

The compulsory courses comprise an introduction and four

subject courses. The four subjects are:

1. Healthcare theory, including the pharmacy profession,

community health, the consumer’s perspective and medi-

cation consumption.

2. Documentation in pharmacy practice, including planning,

performing and evaluating surveys, framework conditions,

theories and methods.

3. Pharmacy practice management, including management

and organisation, Human Resource Manage-ment, busi-

ness development and pharmacy operations.

4. Professional advice and information, understanding con-

sumers’ perspectives and expectations, framework conditions

and methods.

A secretariat has been set up at the School for the specialised

programme in community pharmacy. As well as providing study

guidance, the secretariat will assist during the programme’s in-

troductory phases and ensure that it develops satisfactorily in

terms of practical running and academic content. An adminis-

trator has been appointed to be in charge of secretariat ser-

vices, and a formal co-operation has been set up between the

secretariat and the School’s new specialised programme in hos-

pital pharmacy.

Nineteen pharmacists applied in the first admission round for

the specialised programme in community pharmacy starting

on 1 January 2001. An introductory course was held for them

in April 2001, and the first subject course, Healthcare theory,

was held in August and November 2001. Ten pharmacists

applied for the second admission round for the programme

starting on 1 January 2002.

The Study Board for Specialisation in Community Pharmacy

has prepared a final proposal for the programme’s regulations

and planned the entire programme course, as described in

The Study Guide to the Specialist Programme in Community

Pharmacy. The study board submitted the programme regula-

tions to the Senate, which approved them in November 2001.

At the same time, in accordance with The Development

PHD TRAINING

PAGE 35

Poul R. Kruse: Introducing a specialised programme in community pharmacy.

Contract 2000-2003 between the School and the Ministry of

Education, the Senate adopted a motion for the School to

initiate negotiations with the Ministry as soon as possible to


Hanne Herborg (Head of Research and

Development, Pharmakon) teaches at the new

Specialisation in Community Pharmacy.

approve the specialised programme in community pharmacy

for inclusion in a relevant module of the further and continuing

education system for adults.

The introduction of the specialised pro-

gramme in community pharmacy has at-

tracted broad interest and backing from all

interested parties, as evidenced by several

references to the programme in pharmacy

journals in 2000 and 2001. It has been par-

ticularly satisfying for the School to note that

all the pharmacy profession’s authorities and

organisations have nominated representa-

tives to the study board.

The members of The Study Board for Specialisation in Community Pharmacy:

Poul R. Kruse, Associate Professor, DSc (pharm), Department of Social Pharmacy, nominated by The Royal Danish

School of Pharmacy (chairman)*

Bente Steffansen, Associate Professor, PhD (from 1 September 2001 Associate Professor Janne Rømsing, PhD),

Department of Pharmaceutics, nominated by The Royal Danish School of Pharmacy*

Peter Thygesen, Associate Professor, PhD (from 1 February 2001 Helmer Ring, Professor and Consultant, Doctor of

Medicine), Department of Pharmacology, nominated by The Royal Danish School of Pharmacy*

Kurt Fonnesbæk Rasmussen, Director, MSc (pharm), nominated by Pharmakon a/s*

Kirsten Pultz, project coordinator, MSc (pharm), nominated by Pharmakon a/s*

Susanne Trøck-Nielsen, proprietor pharmacist, nominated by the Danish Pharmaceutical Association

Majken Juul Jensen, pharmacist, nominated by the Danish Association of Pharmacists, of which she is chairman

Bodil Strøh, proprietor pharmacist, nominated by The Danish Pharmaceutical Society

Lars Arboe Harild, examiner (from 1 September 2001, Anne-Marie Vangsted, Head of Division, MSc [pharm]), nominated

by the Danish Medicines Agency

Mikala Vasehus Holck, pharmacist, nominated by participants in the specialised programme for community pharmacists

* Indicates members of the executive committee of the study board

Head of Secretariat: Trine Hopp, MSc (pharm), (from 1 June 2001, Thomas Clemens Jensen, MSc (pharm)), Department

of Social Pharmacy, The Royal Danish School of Pharmacy.

PAGE 36


PAGE 37

Department of Analytical and Pharmaceutical Chemistry

Research at the Department of Analytical and Pharma-

ceutical Chemistry covers the following main areas: analyti-

cal chemistry (involving environmental and bioinorganic chem-

istry as well as chemical toxicology (aimed at accidents with

hazardous chemicals)) and pharmaceutical chemistry (applied

physical chemistry).

RESEARCH

ANALYTICAL CHEMISTRY

Basic research in separation science

The research in analytical chemistry is devoted to basic re-

search in separation science as well as to research in drug

metabolism involving the development of new analytical meth-

ods. The development of new analytical methods is based in

part on basic research. The research in separation science fo-

cuses on separation mechanisms in high-performance liquid

chromatography (HPLC) and capillary electrophoreses (CE).

This research is currently being expanded to cover hyphenat-

ed techniques like HPLC-mass spectrometry (HPLC-MS), CE-

(MS), HPLC-nuclear magnetic resonance (HPLC-NMR) and

eventually CE-NMR.

Spectrometry - especially NMR - is an important part of the

research area, and the potential of using NMR in bioanalytical

chemistry is explored.

A major area of application is drug metabolism, where a

number of drugs are under investigation. The interaction of

reactive metabolites (e.g. glucuronides) with biopolymers is

also studied and structure activity relationships investigated.

Part of the research is conducted in collaboration with other

research groups at the School, at hospital laboratories and in

the pharmaceutical industry.

Research in analytical chemistry also covers determination

of trace elements and their biotransformations. The main in-

terest here is developing new methods of speciation analysis.

The analytical techniques are ion chromatography with chemi-

luminescence detection, graphite furnance atomic absorption

spectrometry and ICP-MS in combination with HPLC and CE.

Supervisors:

Steen Honoré Hansen, professor, Dsc (pharm)

Inga Bjørnsdottir, associate professor, PhD (until September

2000)

Claus Cornett, associate professor, PhD

Bente Gammelgaard, associate professor, PhD

Ole Jøns, associate professor, PhD

Alex Mehlsen Sørensen, associate professor, PhD (until

January 2001)

Jette Tjørnelund, associate professor, PhD (until September

2001)


PAGE 38

Head of Department Professor Steen Honoré Hansen, DSc

DEPARTMENT OF ANALYTICAL AND PHARMACEUTICAL CHEMISTRY

ENVIRONMENTAL CHEMISTRY

Chemical environmental research focuses on the emission of

elements and compounds to the internal or external environ-

ment, and on their processing and effects on these environ-

ments. Environmental chemistry integrates environmental risk

assessment, toxicology, chemistry and applied analytical

chemistry. Current research projects deal with the modelling

of effects of emissions on aquatic ecosystems, effect and

speciation of heavy metals, risk and effect analysis of

medicine, and the relationship between environment and

health and endocrine disruption by xenobiotics, incl. drugs.

Supervisors:

Sven Erik Jørgensen, associate professor, Dsc (Eng)

Bent Halling-Sørensen, associate professor, PhD

Søren Nors Nielsen, external associate professor, PhD

(until June 2001)

ENVIRONMENTAL RISK ASSESSMENT

OF PHARMACEUTICALS

Antibiotics are used widely across Europe to treat farm animals.

Once released into the environment, the pharmaceuticals

and their metabolites may persist and have the potential to

runoff to surface waters or leach to groundwater where they

can impact human and environmental health. Unlike other

classes of substances (e.g. pesticides, metals and nutrients),

the environmental fate of veterinary pharmaceuticals is poorly

BIOINORGANIC CHEMISTRY

The importance of inorganic chemistry in biology, especially

metal ion coordination chemistry, has gained considerable ap-

preciation during the last decade. The discovery of the roles

of metal ions and metalloproteins in health and disease

through genetic and biochemical studies has drawn the at-

tention of molecular and cell biologists in increasing numbers.

Indeed, there are few areas of modern biology where inorgan-

ic chemistry is not destined to make its mark. Thus, inorganic

chemistry combined with molecular biology and protein che-

mistry in studies of metal protein interactions will influence the

thinking and research activities of chemists and biologists in

the future. A little appreciated fact is that the brain is a spe-

cialised organ that concentrates metal ions. So, combining in-

organic chemistry with molecular biology and protein chem-

istry in order to study abnormal metal protein interactions will

undoubtedly lead to a better understanding of the molecular

origin of major neurological diseases.

The overall purpose of our research is to continue and fur-

ther develop studies of the relationship between metal ions

and macromolecules experimentally as well as theoretically, a

field entitled bioinorganic chemistry on the border between in-

organic chemistry and biology. Our collaboration with leading

research groups in other countries, including powerful bio-

technological centres, ensures a continuous integration with

international frontline research in bioinorganic chemistry.

Supervisor:

Ole Farver, professor, DSc

understood. A three-year project is therefore being conducted

involving modelling, laboratory, semi-field and field studies.

The aim of the study is to identify those factors and process-

es affecting the fate of veterinary pharmaceuticals in order to

adapt existing risk assessment models or develop new mod-

els. Laboratory studies will investigate sorption, degradability

and ecotoxicity of a range of veterinary pharmaceuticals. A

range of new analytical methods, LC-MS-MS in particular, will

have to be developed for the purpose.

The results of these studies will be used to assess the

models currently available and, where appropriate, the mod-

els will be adapted to cope with pharmaceuticals. A range of

scenarios will be developed to assess the risk of veterinary

pharmaceuticals.

Supervisors:

Flemming Ingerslev, Anne Marie Jacobsen, Ann-Louise

Steinicke-Larsen, Anne Lykkeberg, Jette Tjørnelund and Bent

Halling-Sørensen together with several international research

groups

Hormonally active agents in the environment

Over the past ten years, it has appeared that a number of en-

vironmental contaminants are able to provoke adverse

changes in endocrine systems in humans and in the environ-

ment. The research within this area has primarily focused on

the development of a test aimed at screening the endocrine

effects of chemicals on the crustacean Acartia Tonsa. At pre-

sent an assay for testing endocrine effects on breast-cancer

cells, the E-screen method, is under development.

The analytical chemical aspects have been put more in fo-

cus in a recently started project. Methods to preconcentrate

surface water are being developed, and analytical methods

(HPLC-MS-MS) and the previously mentioned bioassays are

used in the search for an overall picture of the oestrogen po-

tential of surface waters.

Supervisors:

Henrik Rasmus Andersen, Søren Nors Nielsen, Flemming

Ingerslev and Bent Halling-Sørensen together with the

Technical University of Denmark

CHEMICAL TOXICOLOGY

Based on the simultaneous use of toxicology and chemistry,

information on hazardous substances and accidents involving

such substances has been made available to public authori-

ties, the medical community and others. Several of these in-

quiries have resulted in toxicological investigations. Two main

research branches have appeared: inhalation toxicology (pul-

monary edema, toxic smoke from fires, criteria for evacuation,

etc.) and clinical toxicology (hospital reception and treatment

of patients suffering from the effects of chemical accidents,

antidote preparedness, etc.). Thus the Department functions

as a centre of knowledge on the use of hazardous sub-

stances and accidents involving such substances.

Supervisor:

E. Sonnich Thomsen, associate professor, PhD

PHARMACEUTICAL CHEMISTRY

The pharmaceutical chemistry research programme relates to

optimisation of drug formulation involving prodrug design and

salt formation. Aspects of drug delivery under investigation

encompass factors influencing bioavailability and duration of

drug action. Current research may be divided into four areas

that are more or less interrelated (i) “Manipulation of drug sol-

ubility through prodrug design and salt formation” including

both aqueous and lipid solubility, (ii) “Parenteral depot formu-

lations” with the focus on oil solutions and crystal suspen-

sions, (iii) “Prodrugs - identification of transport groups ex-

hibiting a biological functionality” where we have initiated a

search to identify suitable chemical compounds with signifi-

cant affinity to blood components, and (iiii) “Facilitation of

biomembrane drug transport by prodrug design. Furthermore,

the pharmaceutical chemistry group is engaged in pharma-

ceutical chemical profiling of drug substances including as-

sessment of drug stability. Our research is partly conducted in

collaboration with both internal and external groups.

Supervisors:

Claus Selch Larsen, professor, PhD DSc (pharm)

Helle Brøndsted, associate professor, PhD

Gitte Juel Friis, associate professor, PhD (until December

2000)

Karin Fredholt, associate professor, PhD (until October 2000)

Flemming Madsen, associate professor, PhD (until September

2000)

Søren Nors Nielsen, associate professor, PhD (from June

2001)

Kirsten Eberth, associate professor, PhD

DONATIONS AND GRANTS

Ole Farver gratefully acknowledges support from the Danish

Natural Science Research Council; the Danish Medical

Research Council; the Lundbeck Foundation and the

Novo-Nordisk Foundation.

Bent Halling-Sørensen has together with senior researcher,

PhD Lars Bogø Jensen, SVS received each DKK 375.000 per

year for a two year period (2001-02) from SJVF (Statens

Jordbrugsvidenskabelige Forskningsråd) to the project:


PAGE 40

“Assessment of the fate and resistance development of se-

lected antibiotic metabolites in soil” grant no. 53-00-0279.

Bent Halling-Sørensen and Jette Tjørnelund have received

DKK 4.0 mio from The EU 5th frame programme (project

period 2000-03): Environmental risk assessment of veteri-

nary medicines in sludge (ERAVSMIS). Project no. EESD-

ENV-99-1, EVK1-1999-00034P, for a three year project

Claus Selch Larsen and Helle Brøndsted have received DKK

680.000 from Centre for Drug Design and Transport.

Bent Halling-Sørensen has from the Danish Environmental

Agency received DKK 500.000 for the project ”Drugs and the

environment” projects no. 00-650-24.

Steen Honoré Hansen received DKK 300.000 from the

Danish Medical Research Council for partly financing of a

micro HPLC equipment.

Svend Erik Jørgensens current supported projects are:

Enreca Project with Dar es Salaam University prolonged to

August/September 2003 – DKK 4,3 million and EU-supported

project, coordinator Sovan Lek, Toulouse University, EURO

118.000.

GUESTS

PhD Dina Tawfik Mohammed El-Sherbiny from Mansoura

(Egypt). September-December 2000.

Dr Stig Pedersen from University of Oslo, Norway. October 2000.

Nuria Vives I Llácer from Barcelona, Spain. September-

December 2001.

Dr. Michael G. Rowan from University of Bath, UK. June-

August 2001.

Dr. Paul Blackwell from Cranfied University, England, visited

the environmental chemistry group in February 2001 in order

to work on the development of an analytical method to be

used in a common research project financed by the EU.

PhD student Jianhua Wang, Technical University of Denmark

(1.10.00-30.11.00)

Hu Weiping from Nanjing Institute of Limnology and

Geography, Chinese Academy of Science. Year 2000 Fall.

Santanu Ray, Post.doc. from Calcutta University , January -

April 2001.

Sixtus Kayombo from Dar es Salaam University, August -

November 2001.

ARRANGEMENTS

The Environmental chemistry group arranged (30.7.–10.8.

2001) the course ”Environmental risk assessment of pharma-

ceuticals and chemicals” as part of ”The Øresund Summer

University 2001”. 25 students from 12 different countries par-

ticipated in the course.

PRESENTATIONS

Halling-Sørensen B. Biologically active substances in society

and their environmental fate. Apoteket AB symposium “Vad

vet vi om läkemedel i miljön?” in Stockholm, Sweden (Invited

speaker) 7 June 2001.

Halling-Sørensen B. Occurrence and environmental properties

of antibiotics used in Denmark. Presented at the SETAC

conference Organic soil contaminants 2-5 September 2001 at

Eigtved Parkhus, Copenhagen Denmark.

Hansen SH. “Challenging the principles of setting limits in

pharmacopoeial tests”. The Future Face of the European

Pharmacopoeia Nice, 8-9 February 2001 (Invited lecturer).

Hansen SH. “Hyphenation of CE to ICP-MS and to nano-

spray MS for high sensitivity and selectivity in biomedical

analysis”.14th International Bioanalytical Forum, 3-6 July 2001

at the University of Surrey, Guildford, UK (Invited plenary lec-

turer).

Hansen SH. “The use of microemulsion electrokinetic chro-

matography (MEEKC) and dynamically coated capillaries for

drug analysis by capillary electrophoresis”. 11th International

Symposium on Advances and Applications of Chroma-

tography in Industry. Bratislava, Slovak Republic, 27-31

August 2001 (Invited lecturer).



drug analysis by capillary electrophoresis”. The 8th Annual

AstraZeneca Corporate Electrodriven Separations Sympo-

sium, 17-18 October 2001, Lund, Sweden (Invited plenary

lecturer).



drug analysis by capillary electrophoresis”.CE-Forum, Novo

Nordisk A/S, 11 December 2001 (Invited lecturer).

MEMBERSHIPS OF EXTERNAL COUNCILS

AND BOARDS

Claus Selch Larsen is a member of the Danish Academy of

Technological Sciences, chairman of the Biopharmaceutical

Section, Danish Pharmaceutical Society, member of Fagligt

Forum under The Danish Council for Scientific and Industrial


PAGE 41

Research (until July 2001), member of the editorial board for

Europian Journal of Pharmaceutical Sciences, and member of

the scientific advisory board for the biotech company Zealand

Pharmaceuticals (until June 2001).

Bente Gammelgaard is a member of Centre for Educational

Development in University Science

Bent Halling-Sørensen is external censor at the Technical

University of Denmark.

Steen Honoré Hansen Chairman of The Chromatographic

Society, Scandinavian Section and President of The

Separation Sciences Foundation. Member of the board of

ProPharma A/S and the board of The Propolis Research

Center A/S. Member of the Chemical Working Party and the

Working Party for Natural Products of the Pharmacopoeial

Board in Denmark. Member of the Commission and of the

Expert Group no.10B under the European Pharmacopoeia

Commission, Strasbourg.

Svend Erik Jørgensen is editor in chief of Ecological Model-

ling and Member of ILEC’s scientific committee (International

Lake Environmental Committee). Since 1988 bureau member.

Since 1995 President (chairman). He also spends a lot of his

time as a member of the following editorial boards: Water

Resource Developments, General Systems, Urban Systems,

Environmental Software and Modelling, Ecological Engineer-

ing, Journal of Analytical and Environmental Chemistry, Lakes

and Reservoirs, Research and Management, SAR- and QSAR

in Environmental Research, Environmental Modelling, Ecologi-

cal Indicator (Associate editor in chief) and Ecohydrology.

Member of the board for “The Summer School in Venice”,

1988 - present. Honorary Chairman of ICEI (International

Committee of Environmental Indices). Member of Scientific

Advisory board for IMAR (Marine Research Institute), Coimbra

Portugal, 1998 – present. Referee for IFS (International

Foundation for Science) 1994 - present.

Member of an Expert Panel (5 members), focusing on

Application of Models to develop ERA for chemicals (U.S. -

EPA, 1999 - ). Member of a UNESCO board for

Ecohydrology, 2001- present.

PROJECTS

ANALYTICAL CHEMISTRY

Capillary electrophoresis (CE)

New principles of performing CE with high electroosmotic

flow at low pH have been achived using a number of dynamic

coatings of the internal surfaces of fused silica capillaries. The

principles have been applied in bioanalyses of small as well

as of larger molecules (proteins). Furthermore, this new sepa-

ration technique have been hyphenated to ICP-MS as well as

to sheathless MS which also will inprove the applicability with-

in bioanalyse and thus for use in studies of drug metabolism.

Microemulsions have also been explored for use in drug

analysis, purity testing of drug substances and in bioanalysis.

(Jette Tjørnelund, Jørgen Olsen, Anette Gemal Jensen, Stig

Pedersen-Bjergaard, University of Oslo, Inga Bjørnsdottir,

Dina Tawfik Mohammed El-Sherbiny, Charlotte Gabel Jensen

and Steen Honoré Hansen)

Drug metabolism

The metabolism of drugs are compared in various in vivo

models (liver slices, liver homogenates as well as isolated en-

zyme systems). For this purpose selected drug substances

(e.g. naproxen, tolfenamic acid, ibuprofen, warfarin and dex-

trometrophan) are used as probes. Analytical chemical meth-

ods such as HPLC, HPLC-MS and HPLC-NMR have been

used to study the formation of metabolites in the models test-

ed. The reactivity of phase II metabolites towards proteins

have been an important issue.

A major field is reactive drug metabolites and their possible

role in ideosyncratic drug reactions. Focus has been on acyl-

glucuronides and acyl-CoA-adducts. The formation of CoA-

adducts results in the incorporation of the drug substances

into a number of endogenous metabolic pathways.

(Inga Bjørnsdottir, Claus Cornett, Steen Honoré Hansen,

Rasmus Worm Mortensen, Jørgen Olsen, Nina Hagen, Jette

Tjørnelund, Christian Skonberg, Ulrik Sidenius, Jane K.

Johannessen, prof. Ian T. Wilson, AstraZeneca, UK and prof.

Jeremy K. Nicholson, University of London, UK)

Hyphenation techniques

In order to obtain more data information faster different kinds

of couplings between separation techniques with spectro-

scopic techniques have been studied. Of special interest are

the following couplings: LC-NMR-MS/MS; CE-NMR; CE-

MS/MS; CE-ICP-MS. The LC-MNR-MS/MS hyphenation have

been used for the investigation of constituents and Hypericum

perforatum and other plants. A system for ion pair HPLC-

NMR-MS have also been developed for identification of impu-

rities in basic drug substances.

(Steen Honoré Hansen, Jette Tjørnelund, Claus Cornett,

Anette Gemal Jensen, Jørgen Olsen, Inga Bjørnsdottir, prof.

Ian D. Wilson, AstraZeneca, UK)

Quality control of drug substances

A project that involves development and validation of analyti-

cal chemical methods for determination of identity and purity.

The project is performed in collaboration with members of a

group of experts under the European Pharmacopoeia Commission.

(Alex Mehlsen Sørensen, Steen Honoré Hansen)


PAGE 42

Mononuclear metalloproteins

Intramolecular electron transfer

Intramolecular electron transfer (ET) in bacterial proteins like

the azurins has provided basis for experimental as well as

theoretical studies of biological electron transport. With a

copper ion attached directly to amino acids and without the

presence of foreign group like e.g. heme we have the sim-

plest possible prosthetic group, namely the copper ion itself.

The protein is characteristic with its very robust �-sheet con-

struction and since the three dimensional structure has been

determined for a large group of azurins from different bacterial

origin as well as for many mutated proteins it is an ideal can-

didate for studies of relationships between structure and re-

activity. Systematic exchange of amino acids have provided

important information in this respect, and we now pursue

studies on intramolecular ET in azurin mutants with very large

driving force. We have so far been able to determine the reor-

ganization free energy for a �-sheet protein and determined

the electronic tunneling factor.

Kinetic isotope effects have so far never been treated, nei-

ther theoretically nor experimentally, for the biologically impor-

tant non-adiabatic ET processes. Not only the dynamic pro-

perties for H2O and D2O are significantly different, but also

the local structures of the two solvents vary. These parame-

ters influence the polarization correlation distance and lead to

changes in solvatisation and cause a definite deuterium iso-

tope effect. We have recently published our studies on ther-

modynamic and kinetic isotope effects on azurin.

Another interesting aspect of biological ET is the effect of

polarization on the long distance electronic coupling. Profes-

sor Robert Huber’s group at the Max Planck Instute in

Martinsried has produced a new type of “atomic” mutants

where certain hydrogen atoms in aromatic amino acid

residues have been exchanged by fluorine atoms. This substi-

tution is practically isosteric (the x-ray structures of the pro-

teins have been determined) while the polarity of the fluorinat-

ed side chains has been inverted. We are presently studying

the electronic couplings in these mutants by determining the

rates of ET.

Purple azurin

Structure and spectroscopy

The effect of axial ligand mutation on the binuclear CuA site in

a recombinant azurin bas has been investigated by advanced

magneto-spectroscopic techniques. The changes in the spin

density in the CuA site, as manifested by the hyperfine cou-

plings of the weakly and strongly coupled nitrogens, and of

the cysteine protons, were followed using a combination of

advanced EPR techniques. X-band (9 GHz) electron-spin-

echo envelope modulation (ESEEM) and two-dimensional (2D)

hyperfine sublevel correlation (HYSCORE) spectroscopy were

employed to measure the weakly coupled N-14 nuclei, and X-

and W-band (95 GHz) pulsed electron-nuclear double reso-

nance (ENDOR) spectroscopy for probing the strongly cou-

pled N-14 nuclei and the protons. The high field measure-

ments were extremely useful as they allowed us to resolve the

T2 and CuA signals in the g❑ region and gave H-1 ENDOR

spectra free of overlapping N-14 signals. These effects were

associated with an increase in the Cu-Cu distance and subtle

changes in the geometry of the Cu2-S2 core which are con-

sistent with the electronic structural model we have devel-

oped earlier.


PAGE 43

Multicentered metalloproteins and -enzymes

During the last years we have studied intramolecular ET in

multi centered macromolecules. An important issue which we

want to pursue is the coupling between electron transport

and coordination of the oxidizing substrate (e.g. O2 and NO2).

Gating processes where rearrangements of nuclei often be-

comes rate determining has so far not been studied in suffi-

cient detail, although we have already encountered examples

of intramolecular ET which is controlled by O2-coordination.

CuNiR

Denitrification is one of the most important and concomitantly

one of the most complicated biological ET processes. In col-

laboration with a British group we study the kinetics of enzy-

matic nitrite reduction by the copper containing nitrite reduc-

tase from Alcaligenes bacteria in an attempt to throw light on

the connection between structure, substrate binding, and re-

activity. CuNiR catalyzes the one-electron reduction of nitrite

to NO. We have already publishes results on the native en-

zyme and are presently studying different single site mutated

enzymes.

CD1NiR

The heme containing nitrite reductase from Pseudomonas

bacteria is another respiratory enzyme that we presently

study. Like the above copper enzyme it catalyzes the one-

electron reduction of nitrite to NO as well as the four-electron

reduction of dioxygen to water. Cytochrome cd1 nitrite reduc-

tase is a homodimer, each monomer containing one c-type

and one d1-type heme as prosthetic groups. The interheme

distances across the dimer interface of at least 3.8 nm ensure

electron transfer between monomers to be negligible, howev-

er. CD1NiR constitutes an optimal system for studies of the

connection between intramolecular heme ET and intermolec-

ular ET between substrates and enzyme. There has been

considerable debate about the relevance of structural chan-

ges including ligand switching during redox cycling and the

physiological implications of a possible gating mechanism.

We have already established a cooperativity between the

hemes and a dependence of ET rates on the reduction state

of the enzyme. The first part of our studies is now in print.

(Ole Farver in collaboration with: G.W. Canters, Inst. of

Chemistry, Leiden Universitet; R.R.Eady, Nitrogen Fixation

Lab., Norwich; O. Éinarsdóttir, Dept. of Chemistry and

Biochemistry, UCSC; D. Goldfarb, Dept. of Chemical Physics,

Weizmann Institute; R. Huber, Max Planck Inst. für Biochemie,

Martinsried; P.M.H. Kroneck, Dept. of Biology, Konstanz

Universitet; Y. Lu, Dept. of Chemistry, University of Illinois;

I.Pecht, Dept. of Immunology, Weizmann Institute; Lars K.

Skov, Kemisk Institut, KU; Jens Ulstrup, Kemisk Institut, DTU)

Selenium metabolism in humans

- speciation in biological samples

Selenium is an essential element that exerts its effects via the

selenoproteins and so far more than 30 selenoproteins have

been identified. The biological functions of all these proteins

have not been completely elucidated yet, but some of the

well characterized proteins are involved in antioxidative pro-

cesses in the body. In recent years the element has attract-

ed some attention as a possible protective agent against

certain forms of cancer. The cancer protective effect was

observed after prolonged intake of doses exceeding the

amounts necessary to keep the essential selenoproteins fully

functional. Thus, the the protective effect may be due to

other selenium compounds than the selenoproteins.

However, the metabolism of selenium is far from com-

pletely understood and the majority of earlier studies on se-

lenium metabolism were performed in vitro or in animal ex-

periments.

The main purpose of this project is to separate, identify

and quantify the different selenium containing compunds in

human biological samples - mainly plasma and urin - with

the ultimate aim of improving the understanding of human

selenium metabolism.

This involves the use of hyphenated techniques where dif-

ferent separation systems are coupled to the ICP-MS (Induc-

tively Coupled Plasma Mass Spectrometry) or MS detectors.

The separation techniques comprise chromatographic tech-

niques as reversed phase, ion-exchange and ion-pairing

chromatography together with capillary electrophoresis.

Special interest is taken in development of interfaces be-

tween the separation systems and the ICP-MS detector in or-

der to solve problems with incompatibility between optimum

flow ranges. Furthermore, solutions for circumventing prob-

lems based on the different compatibility of the preferred sol-

PAGE 44


vents between the separation system and the detector are

examined.

As the natural concentrations of the selenium species is at

the low µg/L level and some of the compounds are suspect-

ed to be unstable, different pretreatment procedures are in-

vestigated and stability studies are undertaken.

(Bente Gammelgaard, Ole Jøns, Lars Bendahl, Ole Farver)

Trace multielement analysis in biological material

This project involves the simultaneous analysis of trace ele-

ments with influence on human health with focus on interac-

tion between the elements. The analytical technique is ICP-

MS.

(Bente Gammelgaard, Ole Jøns)

Environmental risk assessment of pharmaceuticals

Antibiotics are used widely across Europe to treat farm ani-

mals.

Once released to the environment, the pharmaceuticals and

their metabolites may persist and have the potential to runoff

to surface waters or leach to groundwaters where they can

impact human and environmental health. Unlike other classes

of substances (e.g. pesticide, metals and nutrients), the envi-

ronmental fate of veterinary pharmaceuticals is poorly under-

stood. A 3 year project is therefore being performed involving

modelling, laboratory, semi-field and field studies. The aim of

the study is to identify those factors and processes affecting

the fate of veterinary pharmaceuticals in order to adapt exist-

ing risk assessment models or to develop new models.

Laboratory studies will investigate sorption, degradability and

ecotoxicity of a range of veterinary pharmaceuticals. To do so

a range of new analytical methods especially on LC-MS-MS

has to be developed.

The results of these studies will be used to assess currently

available models and, where appropriate, the models will be

adapted to cope with pharmaceuticals. A range of scenarios

will be developed to assess the risk of veterinary pharmaceu-

ticals.

(Flemming Ingerslev, Anne Marie Jacobsen, Ann-Louise

Steinicke-Larsen, Anne Lykkeberg, Jette Tjørnelund and Bent

Halling-Sørensen together with several international research

groups)

Hormonally active agents in the environment

Over the past ten years it has appeared that a number envi-

ronmental contaminants are able to provoke adverse changes

in endocrine systems in humans and in the environment. The

research within this area has primarily been focusing on the

development of a test aimed at screening the endocrine ef-

fects of chemicals on the crustacean, Acartia Tonsa. Currently

an assay for testing endocrine effects using on breast-cancer

cells, the E-screen method, is under development.

The analytical chemical aspects

has been put more in focus in a

recently started project. In this

project, methods for precontration

of surface water is developed, an-

alytical methods (HPLC-MS-MS)

and the previous mentioned bioas-

says is used in the search of an

overall picture of the estrogen po-

tential of surface waters.

(Henrik Rasmus Andersen, Søren

Nors Nielsen, Flemming Ingerslev

and Bent Halling-Sørensen togeth-

er with the Technical University of

Denmark)

Parabens, a group of com-

pounds possessing estrogenic

potency in in-vitro assays –

what is the toxicological and

ecotoxicological significance of

these findings?

In the beginning of the 1990´s it was discovered that a variety

of chemical compounds used in various activities such as

agriculture (pesticides), industry (chemicals), food and phar-

maceuticals (preservatives), as well as natural compounds

derived from plants and fungi, posses estrogenic or other

hormonal effects detectable in various in-vitro and in-vivo as-

says. These effects occurred despite their low structural simi-

larity to the natural hormones. The toxicological and ecotoxi-

cological significances of these findings are not always clear.

Such finding often seems to provoke a heavy debate in the

public media and creates an immediate public demand of

banning the chemical in question. Last summer Denmark

faced such a discussion when the public media disclosed

that UV-screens used in e.g. sun lotion to reduce UV-radiation

to the skin, possessed estrogen potency in both an in-vitro

assay and for some of them also in an in-vivo assay. The

newspapers and green organisations claimed an immediate

ban of all sun lotions that contained these UV-screens. As a

result, the population was left with the dilemma of choosing

between two risks. Evolution of sun burns with potential risk

to later develop skin cancer or being exposed to hormonally

active chemicals.

To limit the number of such often hasty conclusions regard-

ing the use of chemicals, risk assessment methodologies

should be much more developed in the direction of a com-

municative management tool in today’s society. The strength

of risk assessment as a management tool is that it provides a

means for handling the “unknowns”. The “unknowns” that in

fact exist for most chemicals are handled by using precau-

tionary principles in such assessment. Furthermore, risk as-


PAGE 45

Mille developing the MCF7 assay

sessment also helps us to identify where we need to enhance

our knowledge and perform more experiments.

The parabens is also an example of recently found “xeno-

estrogens”. In the sections of environmental chemistry and

toxicology at the Royal Danish School of Pharmacy we have

lately studied the parabens. Current literature shows that the

estrogenic potency of the parabens increases markedly with

the size of the molecule as well as with the branching of the

alkyl-substitutents. Figure 1 shows the general structure of

parabens together with the natural estrogen hormone, 17�-

estradiol, and 4-alkylphenols which have been proved as

xeno-estrogens. The figure shows that the parabens does not

resemble 17�-estradiol at all, but that there is some similarity

with alkylphenols. (Alkylphenols were identified as xenoestro-

gens a decade ago based on effects in both rats and fish and

their use is now regulated) Parabens are known to be unsta-

ble in different matrices due to their vulnerability towards ester

hydrolysis.

Parabens are often used in the western world as preserva-

tives for food, cosmetics, pharmaceuticals (used in e.g. solu-

tions for injection or infusion) and health care products. The

compounds are nearly always used as mixtures of several n-

alkyl parabens such as n-methyl-, n-ethyl, n-propyl, and n-

butylparabens, and their branched isomers to broaden the

spectrum of preservation. The compounds are regulated in

Denmark so that a maximum of 300-mg paraben/kg is al-

lowed for preserving food. Furthermore, cosmetics is permit-

ted to contain up to 0.4 % of a single paraben and no more

than 0.8 % of a paraben mixture. No legislation rules the use

of parabens in pharmaceuticals.

We tested the estrogenic activity of a number of

parabens, including both the n-forms and iso-

forms (e.g. both n-butylparaben and iso-

butylparaben) with the so-called E-

Screen assay. In this assay,

a breast cancer cell line (the MCF-7 cells) proliferates due to

the presence of estrogenic active chemicals. In total twelve

parabens were assessed.

Results showed as expected that the proliferation of MCF7

cells increased with the dose of all twelve parabens. The rela-

tive potencies of e.g. 2-ethylhexylparabens and ethylparaben

are 5,500 times and 230,000 lower, respectively, compared to

17�-estradiol. We also found that the iso-parabens were sig-

nificantly more estrogenic than the n-parabens.

The question was now whether these findings could imply

that parabens would be a risk for humans or the environment.

The answer is at present: It is not likely. However, results from

in-vitro testing can of course not standalone. Proper risk as-

sessment should be performed, including other relevant infor-

mations such as physico-chemical data of the chemicals, an-

alytical measurement of paraben mixtures, covering a number

of relevant exposure scenarios to both humans and the envi-

ronment.

To assess the parabens we therefore investigated two rele-

vant scenarios that especially were identified as vulnerable to

humans and to the environment with regard to the identified

exposure routes. In the following we give a very brief sum-

mery of the scenarios and of the calculations included.

In scenario I, we attempt to assess the exposure of para-

bens in pharmaceuticals, dosed as daily injections (Heparin

preserved with methylparaben) to a pregnant woman from the

2th to 35th week of pregnancy. This is the most vulnerable peri-

od of the pregnancy for the foetus to be exposed to the com-

pounds. Other pharmaceuticals containing parabens were also

assessed. It was concluded that the highest calculated risk of

introducing cell deformities in the foetus induced by parabens

was one out of a million, compared to similar data for DES

(synthetic estrogen). This is generally considered as an ac-

ceptable risk. But still, a few questions are left. Some lotions

include the iso-parabens identified as more potent ones. A

similar assessment would need non-existing data for the iso-

parabens or could we for instance use in vivo experiments on

linear parabens to predict the risk of using the branched para-

bens? Furthermore, we do not know if the ester hydrolysis in

e.g. the blood or sewage breaks down the branched com-

pounds as rapid as the linear ones.

In scenario II, similarily, we tried to assess the risk for the

aquatic environment using a scenario covering the sewage

treatment plant. Parabens used in health care products or

cosmetics are transported with sewage water from the shower

or bathtub to the sewage treatment plant. In the environment

parameters such as biodegradation, sorption, hydrolysis, pH

and photolysis may have impact on the resulting concentration

of the compounds in the treated effluent. The calculated or

measured concentration is then compared to effect concen-

trations on relevant species (acute or chronic effects) from dif-

ferent trophic levels of the aquatic food chain. If the calculated


PAGE 46

or measured concentrations in the treated sewage exceed the

effect concentrations times an assessment factor, the com-

pounds may be a risk for the environment. Different scenarios

taking in to account more or less information on the fate of the

parabens, all gave results indicating that the concentrations of

the compounds in the sewage were at least a factor 100 –

1000 below the effect concentrations. But our study also re-

vealed that available data on relevant chronic effect concentra-

tions are very sparse so that more relevant data should be

gathered. In other words a definitive conclusion regarding the

risk of parabens in scenario II can not be given.

Our research study aim to pass a few messages. The pub-

lic media is often ready to conclude that society is facing a

risk connected with chemicals based on too few facts.

1. The chemicals (parabens), even though they exhibit estro-

gen potency in a in-vitro assay, does not impose a risk

using the available informations in relevant scenarios.

2. Furthermore, the same chemicals may (in this case the

parabens), because of a variety of applications, be the

subject of quite different exposure scenarios.

3. The biological and chemical fate of the chemicals are im-

portant informations to include in a risk assessment and

might be quit different for the same compound in different

environments.

A much broader awareness of risk assessment as a man-

agement tool able to communicate risks to society is there-

fore urgently wanted. We should learn to communicate our

conclusions not only based on documented informations but

also on the “unknowns” by using precautionary principles in

the assessment. This would balance the communication to

society of the risk of chemicals.

As a further conclusion we might ad that the present study

needed information from several other disciplines than toxi-

cology in order to fulfil the assessments. Analytical chemistry

could be used both to identify the included parabens in the

formulations and analyse the treated sewage. Furthermore we

needed physical chemistry to assess the stability of the

parabens in different matrices such as blood and sewage.

Knowledge about microbiology and biology were used to

assess the biodegradation and perform the MCF7 assay.

Furthermore good skills in literature survey is important in risk

assessment.

(Henrik R. Andersen, Morten M. Pedersen, Mille Holst-

Jørgensen, Søren Nors Nielsen, Flemming Ingerslev, Erling

Sonnich Thomsen and Bent Halling-Sørensen)

CHEMICAL TOXICOLOGY

For decades this department has served as a center of

knowledge on hazardous chemicals, both on handling and in

case of accidents. The number of calls is about 50 per year.

Several of these inquiries have resulted in further toxicological

evaluations. Two main research branches have appeared: in-

halation toxicology (pulmonary edema, toxic smoke from fires,

criteria for evacuation, etc.) and clinical toxicology (hospital

reception and treatment of patients suffering from the effects

of chemical accidents, antidote preparedness, etc.).

A compulsory course on toxicology is given. An important

aspect is that the students are supposed to have a good

knowledge of chemical compounds and of the properties of

groups of chemicals. The reason is that many of the prob-

lems from worker’s and consumer’s safety, from environmen-

tal pollution and from chemical disasters implies knowledge of

chemistry and toxicology, simultaneously. Similar considera-

tions apply to the safety course at the beginning of the study.

Projects on toxicology and chemical safety:

• Releases of toxic gases from chemical spills or from chem-

ical fires.

• Antidotes and procedures for acute poisonings, especially

if these can be used by laypersons.

• The combination of chemistry and toxicology with technical

and tactical knowledge forms the basis for advising e.g.

the authorities, the politicians, and the media on hazardous

chemicals: the risks and the preventive and mitigative

measures. Unfortunately, this activity becomes increasingly

relevant as the knowledge of chemistry and toxicology de-

creases both for the groups mentioned and in the general

public.

(Erling Sonnich Thomsen)

PHARMACEUTICAL CHEMISTRY

Prolonged release of bupivacaine after subcutaneous in-

jection of an oil mixture formulation in the rat

For decades anaesthesiologists have sought an agent that

would provide local anaesthesia lasting for days rather than

hours. Such an agent would be invaluable for providing post-

operative pain control and for treatment of chronic pain.

Among other characteristics the ideal long acting local anaes-

thetic agent should affect sensory, but not motor fibers. No

agent currently exists that possesses all the desired proper-

ties. Therefore, most efforts have primarily been concerned

with modifying formulations of existing local anaesthetics to

yield new mechanisms that will sustain ultra long duration

anaesthesia.

Bupivacaine is a frequently used local anaesthetic. The

treatment of wound sites with administration of bupivacaine

at or near the end of surgery is common practise. For clinical

use the drug is formulated as an aqueous solution (Marcain®)

and the duration of action is approximately 4-6 hours. The

site of action of bupivacaine is the tissue surrounding the in-

jection area, however, a significant amount of the dose enters

into the blood shortly after the injection. When bupivacaine is


PAGE 47

injected as an aqueous solution it is readily mixed with the tis-

sue fluid and distributed to both the nerve cells and the

blood. High concentrations of bupivacaine in the blood might

give rise to severe cardiac toxicity and therefore have to be

avoided.

A means to obtain prolonged bupivacaine release and at

the same time to minimise toxic side effects, is to incorporate

the drug substance into a formulation from which it is slowly

released. Bupivacaine can be dissolved in vegetable oil mix-

tures (in the free base form). These oils are not miscible with

water and after injection of such bupivacaine oil solutions the

drug has to be released into the aqueous tissue fluid before it

can exert its action. By variation of the composition of the oil

mixture it is possible to vary the bupivacaine release rate from

the oil. As a part of a PhD project bupivacaine was injected

subcutaneously in rats in an aqueous and in an oil

mixture. First, the rats were given Marcain® and one

week later the oil formulation containing the same amount of

bupivacaine was injected. After each injection blood samples

were taken as a function of time and the concentration of

bupivacaine in each sample was determined. As seen from

Figure 2 relatively high plasma concentrations of bupivacaine

is initially obtained after injection of Marcain®, and the con-

centration in the blood declines rather fast with time. In con-

trast, injection of the oil solution gives rise to a relatively con-

stant plasma concentration of bupivacaine over an extended

period of time (up to 24 hours). In addition, compared to

Marcain® the oil solution initially results in much lower blood

concentrations thus minimising the risk of unwanted bupiva-

caine side effects. The study indicates that it might be possi-

ble to design pharmaceutical formulations endowed extended

duration of action.

(Claus Selch Larsen)

1. PARENTERAL DEPOTS:

1a. Pharmaceutical chemical

characterisation of oil solutions

The aim of the project has been to develop and characterise

an in vitro release model to be used in investigations of the

rate of release of drug substances/prodrugs from oil solutions

including a chemical kinetic description of the release pro-

cesses. The model has been used to study the influence of

various formulation factors on the control of the rate of drug

release from oil formulations. Furthermore the model has

been used to establish an in vitro-in vivo correlation.

(Dorrit Bjerg Larsen (PhD student), Karin Fredholt (H.

Lundbeck A/S) and Claus Selch Larsen)

1b. Design of prodrugs of polar drug substances aiming

at obtaining depot effect after parenteral administration

Polar drug/model drug substances under investigation include

nicotinic acid, local anaesthetics and dipeptides. The focus of

the project embraces: (i) development of an in vitro release

model for the assessment of the rate of release of lipophilic

prodrug derivatives from oil solutions, (ii) comparison of (a) po-

tential lipase mediated degradation of clinically used oil vehi-

cles, and (b) the rate of disapperance of such oil vehicles from

the injection site after i.m. and s.c. injection in pigs, and (iii)

enhance oil solubility of polar drug candidates by using the

prodrug approach in combination with hydrophobic ionpairing.

(Susan Weng Larsen (PhD student), Gitte Juel Friis (Coloplast

A/S), Michael Ankersen (Novo Nordisk), and Claus Selch

Larsen)

1c. Design of low solubility salts of drug substances

The project aims at achieving greater insight into the effect of

structural parameters on the solubility of salts and the estab-

lishment of models for the prediction of aqueous solubility of

PAGE 48

A group of rats were given the same amount of bupivacaine by subcutaneous injection first as an

aqueous solution and second as an oil solution.

Plasma (blood) concentrations of bupivacaine determined after different time periods after subcuta-

neous injection in rats of the aqueous Marcain® solution (circles) and the oil solution (triangles).

ANNUAL REPORT 2000–2001P

lasm

a co

ncen

trat

ion

(ng/

ml)

Time (hours)

salts. A particular focus area is the formation of low solubility

salts of drug substances containing a carboxy or amino

group. The project includes preparation and pharmaceutical

chemical characterisation of salts, and in addition, aspects of

the design of in situ crystal suspension formulations.

(Henrik Parshad (PhD student), Karla Frydenvang and Tommy

Liljefors (Dept. Medicinal Chemistry), and Claus Selch Larsen)

2. PRODRUGS – IDENTIFICATION OF TRANSPORT

GROUPS EXHIBITING A BIOLOGICAL FUNCTIONALITY:

2a. Optimisation of oral bioavailability of drugs by avoid-

ance of first-pass metabolism

Many potential drug candidates are highly metabolised after

oral administration due to first-pass metabolism in the liver. It

is known that binding of drugs to tissue and plasma proteins

are important parameters influencing the metabolism and

elimination of such compounds. By using the prodrug ap-

proach the aim of this project is to investigate the feasibility of

incorporation of a biological functionality in the transport

group in order to circumvent or minimise liver first-pass

metabolism. As a start efforts will be devoted to identify

chemical structures (fatty acid-like structures) as transport

groups possessing optimal affinity to human serum albumin.

(Jesper Østergaard (PhD student), Helle Brøndsted, Lars

Dalgaard (H. Lundbeck A/S), and Claus Selch Larsen)

3. FACILITATION OF BIOMEMBRANE DRUG

TRANSPORT BY PRODRUG DESIGN:

3a. Prodrugs of nucleotide bases

Oligonucleotide-based therapy might be considered as a new

and highly specific tool for the treatment of diseases such as

cancer and virus infections. The therapeutic use of antisense

oligonucleotides is, however, hampered due to instability of

the backbone. In addition, the polar character of the

molecules is an impediment for their passage of biological

membranes. The aim of the project is (i) to optimise passive

transport of such agents over the bacterial cell wall by pro-

drug derivatisation, and (ii) to investigate the influence of the

physicochemical properties of such derivatives on the rate of

release from pharmaceutical matrices.

(Karsten Petersson (PhD student), Helle Brøndsted, Karen

Krogsfelt (Statens Serum Institut), and Claus Selch Larsen)

3b. Prodrug types of isoxazole structures

An interesting class of GABAA antagonists share an isoxazolol

ring. The polar nature of this ring structure at physiological pH

is less optimal as regards transport over biological mem-

branes. Such pharmacologically active agents may therefore

not be effectively delivered to their site of action: the central

nervous system. The aim of the project is to identify suitable

prodrug types for the isoxazolol structure which combine im-

proved transport properties with desirable cleavage rates.

(Bente Frølund (Dept. Medicinal Chemistry) and Claus Selch

Larsen)

4. MANIPULATION OF DRUG SOLUBILITY:

4a. Use of the combination of prodrug design

and salt formation - a strategy to enhance

aqueous solubility of drugs

By modern medicinal chemistry a great number of com-

pounds exhibiting desired receptor profiles emerge. Unfor-

tunately, insufficient water solubility resulting in low and vari-

able bioavailability after oral administration prevents many

pharmacologically interesting chemical entities from further

development. Improvement of this basic physicochemical

property might be achieved by employing the prodrug ap-

proach which involves only a transient masking of the physic-

ochemical properties since the parent active agent is regener-

ated in vivo. Furthermore, it is well known that the use of dif-

ferent counterions can result in salts differing several orders of

magnitude with respect to aqueous solubility. Thus, the aim of

the project is to enhance the aqueous solubility of poorly wa-

ter-soluble compounds achieved by the combined approach

involving prodrug design and optimisation of salt formation.

(Anders Bach Nielsen (PhD student), Anders Buur (H.

Lundbeck A/S), Karla Frydenvang and Tommy Liljefors (Dept.

Medicinal Chemistry) and Claus Selch Larsen).


PAGE 49

Department of Medicinal Chemistry

PAGE 50

Head of Department: Ulf Madsen, Associate Professor, PhD teaching gives students in-depth knowledge of organic chem-

istry, and integrates chemistry and biology into the process of

educating drug experts.

RESEARCH

The research profile of the Department is illustrated by the fig-

ure below and the general description of the research groups.

More detailed descriptions of selected projects are given un-

der Projects.

The Department of Medicinal Chemistry conducts teaching

and research in organic chemistry, spectroscopy, medicinal

chemistry, natural products chemistry, pharmacognosy and

structural chemistry. All subjects are related to drug research

and because virtually all drugs used in therapy today are or-

ganic compounds, detailed knowledge of organic chemistry

and chemical structure is indispensable for drug experts. The

Research areas at the Department.


PHARMACOGNOSY

The Pharmacognosy Group works with medicinal plants in

teaching and research. The research projects comprise a

range of disciplines from ethnobotany and chemotaxonomy

to bioassay guided fractionation of plant extracts and purifi-

cation of active compounds. Plant material is obtained from

the Tropics, mainly African countries (Burkina Faso, Kenya,

Nigeria, and Zimbabwe), the Mascarene Islands (Reunion and

Mauritius), as well as India and other Asian countries (Vietnam).

Plants used in traditional medicine are studied in selected bi-

ological assays for antimicrobial, antihypertensive, anthelmin-

tic and antimalarial activity. Most of these projects are carried

out as joint venture projects with scientists from tropical

countries and with colleagues from the Royal Danish School

of Pharmacy and other Danish research laboratories.

NATURAL PRODUCTS

In search of new leads with novel pharmacological properties,

it is of interest to test large numbers of compounds.

Therefore, the use of combinatorial libraries is of particular im-

portance to drug discovery. Nature provides an unsurpassed

source of chemical diversity, and combinatorial libraries of

natural products are an important supplement to synthetic

combinatorial libraries. Studies of natural products and of

their potential as drugs are the basic activity of the group.

Research includes plant selection, pharmacological charac-

terisation of the extracts, dereplication, structure elucidation

(mainly by NMR methods), phar-

macological characterisation of

pure constituents, and medicinal

chemistry in relation to promising

structures.

STRUCTURAL CHEMISTRY

The three-dimensional structures

of molecules provide important in-

formation about the properties of

the molecules, and thereby a key

to understanding the relationships

between molecular structure and

biological activity. The Structural

Chemistry Group uses experimen-

tal methods like X-ray crystallo-

graphy to determine the three-

dimensional structure of low-

molecular weight compounds,

macromolecules, e.g. receptors

and enzymes, and protein-ligand

complexes. Computational methods

like molecular mechanics and quantum mechanics are used

to predict molecular properties and to calculate molecular in-

teractions between the ligands (neurotransmitters, hormones,

enzyme inhibitors etc.) and their macromolecular target mole-

cules (receptors, enzymes etc.). By studying molecular inter-

actions, it is possible to construct so-called 3D-QSAR’s

(three-dimensional quantitative structure-activity relationships),

which enable new ligands to be designed and their biological

activity and selectivity predicted.

NEUROMEDICINAL CHEMISTRY

The goal of the Neuromedicinal Chemistry (NeMe) Group is to

design tools and model drugs, which interact specifically with

the target receptors. Bioisosteric principles (molecular mimi-

cry) are used extensively to transform endogenous transmitter

substances or naturally occurring compounds into receptor

specific model drugs. Structure-based design of new ligands

is performed in collaboration with the Structural Chemistry

Group. This is an integral part of the projects aiming at recep-

tors where sufficient data on the receptor proteins are avail-

able. An important aspect of all of these projects is to design

and synthesise the target molecules with established stereo-

chemistry. The enantiomers of pharmacologically active com-

pounds are frequently obtained by optical resolution methods

based on diastereomeric procedures or chiral chromato-

graphic (HPLC) separation techniques. Normally, the absolute

stereochemistry of enantiomers is established by X-ray crys-

tallographic methods supported by circular dichroism and

DEPARTMENT OF MEDICINAL CHEMISTRY

PAGE 51

HPLC parameters. Molecular pharmacology has become an

integral component of modern medicinal chemistry, and the

research activities of this part of the NeMe Group involve re-

ceptor cloning and pharmacological studies using mutated

and chimerised receptors. The NeMe Group has extensive

collaborative projects with the drug industry.

SYNTHETIC CHEMISTRY

The Synthesis Group is involved in the development of a

broad range of new synthetic methods and advanced tech-

niques including metalation reactions, transition metal cata-

lysed reactions, cyclisations and stereoselective processes.

The target molecules are diverse but frequently compounds

of biological relevance. The metalation reactions deal with the

preparation of mainly lithium, magnesium, zinc, boron, silicon

and tin compounds. Transition metal chemistry is focused on

palladium catalysed cross-couplings establishing C-C, C-N

and C-O bonds and is used, for example, in arylation and

heteroarylation reactions. Anionic cyclisation is another impor-

tant subject. Special attention is paid to monoselective, re-

gioselective and stereoselective protocols. Selectivity is

achieved by the use of designed directing, activated, or su-

peractivated groups in combination with suitable protecting

groups. Target compounds range from functionalised 5-mem-

bered nitrogen heterocycles, unnatural amino acids, peptides,

neurotransmitter analogs, bioisosters, prodrugs, transporter

conjugates and lipids to chiral ligands and acylation catalysts

for peptide synthesis. The studies include computational

methods with the aim of predicting reactivity, elucidating re-

action mechanisms and creating rules for rational design of

reaction sequences. Computations are also used to optimise

structural design. NMR-spectroscopy is used extensively for

structure elucidation and to establish correlations between

NMR parameters and physical and chemical properties.

TEACHING

The Department offers the following compulsory courses:

Organic Chemistry • Bioorganic Chemistry • Pharmacognosy

• Drug Design and Development. The courses in Organic

Chemistry and Pharmacognosy include laboratory training in

addition to lectures and class teaching.

The following elective courses are offered:

Spectroscopy • Medicinal Chemistry • Structural Chemistry •

Advanced Organic Chemistry • Phytochemistry, Pharmaca

and Toxins • Etnopharmacology • Herbal Medicines •

Intellectual Property Rights in Pharmaceutical Sciences.

Approximately 30 PhD students are enrolled at the

Department, three-quarters of them financed by external

funding.

The following PhD courses (taught in English) are offered:

Advanced Techniques in Synthetic Organic Chemistry •

Advanced Structural Chemistry and Molecular Modelling •

Receptor Structure and Function • Drug Design and

Discovery • In Vivo Neuropharmacolgy.

SCIENTIFIC GUESTS

Prof. Marco de Amici, Universita di Milano, Italy.

Dr Karine Audouze-Taboureau, NeuroSearch A/S, Ballerup,

Denmark.

Sir, Prof. Tom L. Blundell, University of Cambridge, United

Kingdom.

Prof. Lars Bohlin, University of Uppsala, Sweden.

Prof. Guiseppe Campiani, Universita’ degli Studi di Siena,

Italy.

Dr Paolo Conti, Universita di Milano, Italy.

Dr Caterina Fattorusso, Universita’ degli Studi di Siena, Italy.

Dr Michael H. Howard, DuPont Company, USA.

Dr Henry Hägerstrand, Åbo Akademi University, Finland.

Dr Elisabeth Marseglia, Cavendish Laboratory, Cambridge,

United Kingdom.

Dr Roman Laskowski, Birkbeck College, University of

London, United Kingdom.

Dr Hellen A. Oketch-Rabah, University of Nairobi, Kenya.

Prof. Algirdis Sackus, Kaunas University of Technology,

Lithuania.

Dr D. Shankar, Foundation for Revitalization of Local Health

Traditions, Bangalore, India.

Dr Tracy Spalding, Acadia Pharmaceuticals, San Diego,

California, USA.

Prof. Ronald Stenkamp, University of Washington, Seattle,

USA.

Prof. Olov Sterner, University of Lund, Sweden.

Dr Owe Wiborg, Aarhus University Hospital, Aarhus,

Denmark.

Prof. Jean-Marie Wurtz, Institut de Genetique et de Biologie

Moleculaire et Cellulaire, France.

GUESTS RESEARCHERS

PhD student Luca Guandalini, August-December 2001.

Dr Sonata Krikstolaityté, Kaunas University of Technology,

Lithuania, September 2000-June 2001.

Dr Elin S. Olafsdottir, University of Iceland, June-August

2001.

Dr Michael G. Rowan, University of Bath, United Kingdom,

July-August 2001.


PAGE 52

ARRANGEMENTS

“Nordic Pharmacognosy Meeting”, June 2001.

Mini-symposium “Receptor Structure and Function”, May

16, 2001.

DANSYNC, Danish Centre for Synchrotron Based

Research, Annual Meeting, May 23, 2001.

Minisymposium “Drug Design Copenhagen 2001”, October

16, 2001.

“Seminars in Natural Products and Pharmacognosy” are a

monthly event at the Department.

MEMBERSHIP OF EXTERNAL COUNCILS AND BOARDS

Anne Adsersen

• Member of the Subcommittee on Pharmacognosy under

the Danish Pharmacopoeia Commission.

Mikael Begtrup

• Member of the steering group for the Department of

Physics and Chemistry, The Teaching University of

Denmark.

• Member of the Evaluation Center’s board for assessment of

the universities teaching in physics, mathematics and

chemistry.

• Member of the steering group and the scientific committee

for the 32nd Chemistry Olympiad.

• Member of the scientific committee for the European

Colloquia on Heterocyclic Chemistry.

• Member of the editorial board for Chemical Communi-

cations.

• Scientific editor for ARKIVOC, an electronic journal for

organic chemistry.

Hans Bräuner-Osborne

• Member of the Management Committee of the European

Federation for Medicinal Chemistry.

• Member of the board for the Danish Society for

Pharmacology and Toxicology.

Søren Brøgger Christensen

• Chairman of ”Studiefonden” of the Danish Union of

Pharmacists.

• Member of a panel, which evaluated the Department of

Horticulture, the Danish Institute of Agricultural Sciences,

Årslev.

Karla Frydenvang

• Member of the Danish National Committee for

Crystallography.

Lene Gudiksen

• Head of the Subcommittee on Pharmacognosy.

• Member of the Danish Pharmacopoeia Commission.

• National Representative in ESCOP (European Cooperative

for Phytotherapy) scientific committee.

Jerzy W. Jaroszewski

• Chairman of the Danish Chemical Society, Section of

Organic Chemistry.

Birthe Jensen

• Rector until May 1, 2001.

• Member of the board of UNI.C.

• Member of the board of MVA (Medicon Valley Academy).

• Member of the board of the Symbion Foundation until May

1, 2001.

• Member of the board of European Association of Faculties

of Pharmacy (EAFP).

• Chairman of board of the ULLA network until December 31,

2001.

• Chairman of Evaluation Panel, Pharmacy Education of

Helsinki University, December 2001.

Jette Sandholm Kastrup

• Member of the board for DANSYNC, Danish Centre for

Synchrotron Based Research.


• Member of the Danish Academy of Sciences and Letters.

• Member of the Danish Academy of Technical Sciences.

• Member of the Danish Academy of Natural Sciences.

• Member of the board of directors of the Carlsberg

Foundation.

• Member of the board of Carlsberg A/S.

• Chairman of the board of the Carlsberg Laboratory.

• Vice-chairman of the board of the Alfred Benzon

Foundation.

• Member of the Danish Rector’s Conference.

• Member of the board of the Symbion Foundation.

• Member of the board of the Danish Research Training Council.

• European editor of Journal of Medicinal Chemistry.

• Member of the editorial boards of 7 medicinal chemistry

and pharmaceutical journals.

Tommy Liljefors

• Member of the Management Committee of COST

(European Co-operation in the Field of Scientific and


PAGE 53

Technical Research) Action D13: “New molecules towards

human health care”.

• Member of the editorial board for Journal of Molecular

Graphics and Modelling.

Per Mølgaard

• Co-ordinating secretary for The International Tundra

Experiment (ITEX).

• Danish contact for the ethnobotanical section of AETFAT

(Association for the Taxonomy Study of the Flora of Tropical

Africa).

Nina Rønsted

• Member of the Council for Health Studies and Education.

Ulla Wagner Smitt

• Treasurer of The International Society for Ethnopharmacology.


Mikael Begtrup

DKK 100,000 – Carlsberg Research Prize (Carlsberg

Forskerpris).

Co-financing of a 300 MHz NMR spectrometer from the

Danish Council for Natural Sciences.

Financing of 1 PhD student from Løvens Kemiske Fabrik.

Co-financing of 5 PhD students and 1 post doc from Novo

Nordisk A/S.

Co-financing of 5 PhD students from Lundbeck A/S.

Hans Bräuner-Osborne

DKK 300,000 from The Danish Medical Research Council

for the project ”Molecular pharmacology and mechanistic

studies of family C G-protein coupled receptors”.

For additional research centre grants see ”Research Centres

Grants”.

Søren Brøgger Christensen

DKK 500,000 a year from the Danish Cancer Society

(Kræftens Bekæmpelse) for the project ”Development of tis-

sue-specific prodrugs for treatment of prostatic cancer”

(1.1.02-31.12.04).

USD 70,000 from the National Cancer Institute, Maryland,

USA for development of methods for large-scale isolation and

prodrug preparation of Thapsigargin.

Danida ENRECA project ”The Accra-Copenhagen Research

Link: Malaria Research Programme” (1999-2003).

A grant together with Karen Krogfelt (Statens Seruminstitut)

from the Danish Medical Research Council for the project

”Anti-adhesion therapy” (1999-2002).

Rasmus Prætorius Clausen

DKK 1,140,000 from the Lundbeck Foundation in a 3-year

period.

Henrik Franzyk

DKK 2,997,000 from the Danish Technical Research

Council for the Talent-project “Solid-phase Synthesis of

Neuroactive Polyamine Derivatives”.

DKK 150,000 from the Carlsberg Foundation to support this

research.

Karla Frydenvang

DKK 495,000 from Alfred Benzon Foundation for the pro-

ject ”Solid state properties of pharmaceutically relevant com-

pounds” (31.8.01-30.8.02).

Jerzy W. Jaroszewski

DKK 3,500,000 from Apotekerfondet for purchase of NMR

equipment.

DKK 250,000 from the Danish Medical Council for the pro-

ject ”Analogues of polyamine wasp toxins”.

DKK 254,058 from the Novo Nordisk Foundation for the

project ”Selective antagonists at ionotropic receptors”.

DKK 25,000 from Ben-Gurion University, Israel, for studies

of Balanites.

Danida ENRECA project ”Ethnopharmacology of Indian

medicinal plants” (expired in June 2001)

Danida ENRECA project ”Medicinal plants from East Africa”.


Grants”.

Christina Kasper

DKK 391,636 from the Carlsberg Foundation for the project

”Studies of glutamate receptors with speciel reference to

structure-based drug design” (1.1.01-31.12.01).

Jørgen Bonefeld Kristensen

DKK 62,712 from Novo Nordisk A/S - a one-year Novo

Nordisk Scholarship.

Ingrid Kjøller Larsen

DKK 70,000 from DANSYNC, Danish Centre for

Synchrotron Based Research.

DKK 250,000 from the Danish Medical Research Council

for the project ”Protein crystallography in drug research.

Structure determination of biomacromolecules and their com-

plexes with ligands/drugs (2001-2003)”.

DKK 80,000 from the Novo Nordisk Foundation for the pro-

ject ”Protein crystallography in drug research. Characterization

of biomacromolecules by dynamic light scattering”.


Grants”.


PAGE 54


DKK 1,836,000 from the ”Drug Design and Transport Centre”

granted by the Danish Medical Research Council (account-

ing year 2000-2001).

ECU 177,00 together with Jerzy W. Jaroszewski from EU.

DKK 400,000 from the Alfred Benzon Foundation.


Grants”.

Per Mølgaard

DKK 150,000 from the Commission for Scientific Research

in Greenland for the project ”Development of analytical

methods for secondary compounds in Arctic plants”.

DKK 180,000 together with Søren Brøgger Christensen from

Danida via a grant to Ole Skovmand, Intelligent control for

supporting an environmental project in Burkina Faso, Africa.

DKK 210,000 from the Danish Research Council for the

project ”Special chemicals and pharmaceuticals from plants”.

Britt Petersson

PhD grant from DANSYNC, Danish Centre for Synchrotron

Based Research (2000-2003).

RESEARCH CENTRES GRANTS

Povl Krogsgaard-Larsen, Ingrid Kjøller Larsen and Tommy

Liljefors: DKK 6,000,000 from the Lundbeck Foundation for

the research programme ”Neuro-medicinal chemistry.

Molecular design, specificity and recognition” (1999-2001).

Povl Krogsgaard-Larsen, who is the co-ordinator of this pro-

gramme received DKK 1,150,000 per year. Ingrid Kjøller

Larsen and Tommy Liljefors each received DKK 425,000 per

year.

Hans Bräuner-Osborne , Jerzy W. Jaroszewski, Ingrid Kjøller

Larsen and Tommy Liljefors

DKK 6.700.000 from the research centre NeuroScience

PharmaBiotec A Strategic Drug Research Centre” (1997-

2001). The centre is granted by Danish Medical Research

Council with totally DKK 29,700,000. Povl Krogsgaard-

Larsen is director of the centre.

Ingrid Kjøller Larsen, Tommy Liljefors, Jerzy W. Jaroszewski

and Povl Krogsgaard-Larsen: DKK 635,000 from the

PharmaBiotec funding, which from January 2000 became a

part of the annual appropriation to the Royal Danish School

of Pharmacy (until January 2000 PharmaBiotec was funded

by the State Biotechnology Programme).

PROJECTS

Special chemicals and pharmaceuticals from plants

There is a great need for medicinal plant products of a high

quality, and Danish agriculture is interested in alternative crop

plants to the traditionally grown cash crops. Our research

work comprises plant chemicals like fatty acids, caffeic acid

derivatives, alkamides and iridoids for technical and medicinal

purposes. These compounds are all plant derived, and in

most cases there is only little information of how to grow

these plants, especially under Danish conditions. To deter-

mine the quality of medicinal plants validated analytical meth-

ods are highly important, and a major part of the project is

confined to the establishment of validated analytical methods.

In connection with plant production, diurnal and seasonal

variation in plant secondary compounds may play a central

role.


Echinacea purpurea, the purple coneflower, cultivated in Tåstrup for investigation of a potential

seasonal variation in the content of cichoric acid and alkamides.

PAGE 55

The project has run over the latest five years with financial

support from the Danish Research Councils. Within the pro-

ject emphasis has been put on plants with content of fatty

acids, plants with caffeic acid derivatives and plants with iri-

doids, all with potential use in the technical and pharmaceuti-

cal industry directly or after derivatization.

Caffeic acid derivatives are important antioxidants and ma-

jor ingredients of many plants commonly used in herbal reme-

dies. Main emphasis has been given to Echinacea purpurea

in an attempt to give guidelines for production and use in

Denmark. Evidence of the activity of the compounds in

Echinacea is still lacking, and we have ongoing investigations

of the biological activity of the major constituents, cichoric

acid, alkamides and polysaccharides. As a first result we have

verified the activity of cichoric acid as an antioxidant compa-

rable to rosmarinic acid.

Iridoids are compounds of restricted occurrence in the plant

kingdom, often confined to the same taxonomic groups as

contains caffeic acid derivatives, although these are more

widespread. They are very promising as starter material for

the synthesis of pharmacologically active compounds to be

used in the treatment of cancer or HIV. In a taxonomical study

of the genus Plantago we are making use of DNA sequencing

and the chemotaxonomic value of iridoids and caffeic acid

derivatives characteristic for this taxon. Iridoids and caffeic

acids are common in the whole order of Scrophulariales, incl.

Plantaginaceae, with a number of potential medicinal plants.

(Per Mølgaard, Kim Itenov, Nina Rønsted, Line Sandager,

Søren Johnsen, Line Thygesen and Peter Christensen in col-

laboration with Henrik Franzyk [the Natural Products Group],

Claus Cornett [Department of Analytical and Pharmaceutical

Chemistry]), Søren Rosendal Jensen, [Department of Organic

Chemistry, the Technical University of Denmark] Poul

Flengmark [Danish Agricultural Research Institute, Research

Centre Flakkebjerg] and Leif Skibsted [Department of Food

Chemistry, Danish Agricultural University]).

The ENDOD project for the control of schistosomiasis

transmitting snails

This project is carried out in cooperation with a Zimbabwean

counterpart and the Danish Bilharziasis Laboratory (DBL) and

is dependent on financial support from Danida to DBL. The

aims are to facilitate the cultivation of the Endod plant (Phyto-

lacca dodecandra) and application of the molluscicidal berries

to infected water, in an integrated control of schistosomiasis

(Bilharziasis), a tropical water related disease, where fresh

water snails are crucial for transmission of the parasite.

Control of the intermediate host snails supports the other as-

pects of the general control of schistosomiasis, which affects

more than 200 mio. people in the Tropics.

In the reference period a sociological study of community

participation was completed by a PhD student from Zimbabwe.

His study concerned introduction of the Endod-plant as an

easily grown and locally applied snail control measure. This

should offer a low cost - low technology self help device in

combination with chemotherapy, improved water and sanita-

tion, and health education in the control of schistosomiasis.

See also: www.dfh.dk/activities/endod/index.htm.

(Per Mølgaard in collaboration with Ebba Holme Hansen

[Department of Social Pharmacy), Peter Furu [Danish

Bilharziasis Laboratory], Addmore Ndekha [Blair Research

Laboratory, Harare, Zimbabwe]).

Ethnopharmacological studies of plants

from Réunion Island

This project investigates plants used in traditional medicine in

Réunion Island and plants related to traditionally used plants.

Recent studies include three endemic Melicope species (syn-

onym Euodia), M. borbonica, M. coodeana and M. obscura

selected on basis of their biological activity in preliminary

screening assays. The three species showed significant in vit-

ro antibacterial, antifungal, antimalarial and/or antioxidative

activities.

From the leaves of M. borbonica, 15 constituents have

been isolated and identified. The antifungal activity could be

assigned to xanthoxyline and scoparone, present in very high

concentrations, as well as to limettin and 1,4-epidioxy-bis-

abola-2,12-diene. These compounds showed inhibition of the

in vitro growth of Candida albicans and Penicillium expansum.

The two major methoxyflavones from the leaves inhibited the

NF-�B transcription factor.

Three flavones, 5,7-dihydroxy-3,8-dimethoxy-3’,4’-methyl-

enedioxyflavone (1), 5,7-dihydroxy-3,6,8-trimethoxy-3’,4’-

methylenedioxyflavone (2) and 5,7-dihydroxy-3,6,8,3’,4’-pen-

tamethoxy-flavone, out of five isolated from M. coodeana

were new structures and the presence of the unusual methyl-

enedioxyflavones in this species is of chemotaxonomic impor-


PAGE 56

New compounds from Melicope coodeana.

1: R = H

2: R = OCH3

tance. From M. coodeana compounds with antimalarial and

antioxidative activity have been isolated but the structures not

finally elucidated.

Four compounds with antibacterial and antifungal activity

have been isolated from M. obscura.

(Anne Adsersen, Ulla Wagner Smitt, Henrik Toft Simonsen in

collaboration with Jerzy W. Jaroszewski [The Natural Products

Group]), Dominique Strasberg [University of Réunion]).

Secondary plant compounds in Arctic plants

This project is linked to ITEX - the International Tundra

Experiment

(http://www.systbot.gu.se/research/ITEX/itex.html), which is a

circumpolar co-operation with stations at more than 20 sites

in the arctic area. By observation and manipulation with se-

lected, wide spread plant species, the aims are to anticipate

the reaction of these plants and the environment they occur

in to an eventual global climate change. The observations and

manipulations are carried out after the same instructions at all

sites.

Our contribution mainly concerns plant secondary con-

stituents, and the effect on these compounds of a change in

weather conditions in the Arctic. These compounds are of im-

portance in relation to protection against herbivory and are

probably affected by increased temperatures, which may lead

to a change in relative reproductive success. The main em-

phasis is put on chemical compounds in Salix arctica,

Papaver radicatum, Cassiope tetragona, and plant phenolics

in general. As arctic plants have not been thoroughly investi-

gated, we have so far been able to identify two genuine com-

pounds new to plants.

(Per Mølgaard, Karen Christensen, Anette Lauritzen, Jakob

Tjelum, in collaboration with Claus Cornett [Department of

Analytical and Pharmaceutical Chemistry]).

Optimisation of the antiplasmodial effect

of the natural product licochalcone A

The antiplasmodial and antileishmanial activities of Chinese

licorice roots (Glycyrrhiza inflata) has been related to the con-

tent of licochalcone A. Orally administration of this compound

to mice infected with malaria clears the infection efficiently but

only in relatively high doses. This drawback might be related

to a poor absorption of the drug from the stomach or guts.

The structure of licochalcone A enables syntheses of a

large numbers of analogues and thereby facilitates medicinal

chemistry studies. A positive relation between the chemical

structure and biological activity has previously been proven (a

QSAR model) but the model is only valid for poorly water-sol-

uble analogues. A number of water-soluble analogues were

prepared and their ability to kill malaria parasite in vitro were

determined. A poor variation in their biological activities pre-

vented development of a QSAR-model.

(Klaus Jensen, Søren Brøgger Christensen).

Structure and pharmacology of natural products

Structure elucidation and biological characterisation of natural

products is a mainstream activity of the Natural Products

group. The research is currently focused on antiprotozoal

compounds. The group’s own biological laboratory performs

drug-sensitivity assay using various strains of Plasmodium

parasites as well as assays for cytotoxic activity using wild

type and multidrug-resistant human cancer cell lines, available

via collaboration with National Cancer Institute, Bethesda,

USA. Studies of effects of natural products on Plasmodium

falciparum involve investigations of their action on erythrocyte

membrane, as it was recently discovered, that incorporation

of various compounds into the lipid bilayer of erythrocytes, in

which the malaria parasites are cultured, inhibits indirectly the

parasite growth and invasion. This effect appears as a false

positive result in the in vitro assay. Further studies of nature of

the effect of erythrocyte membrane modifications on parasite

growth are in progress.

Studies of phytochemical and pharmacological effects of

natural products involve investigations of alkaloids from Apo-

cynaceae, Asclepiadaceae, Periplocaceae and Flacourtiaceae.


PAGE 57

Cassiope tetragona, a dwarf shrub from Disko Island in Westh Greenland.

The shoots contain a great variation in essential oil, and several benzoic

acid derivatives of which a methyl ester is new from plants.

During the period covered by this annual report, many novel

phenanthroindolizidine alkaloids, cytotoxic at the nanomolar

level, have been identified. Iranian Perovskia species have

been identified as a new source of tanshinones, clinically use-

ful natural products originally isolated from the

Chinese drug dan-shen. Several highly leishmani-

cidal, novel isoflavans have been isolated from

Smirnowia species. Novel terpenoids belonging

to malabaricane and aromadendrane series have

been identified from Apocynaceae and Flacour-

tiaceae, respectively.

The core-activity of the group is NMR and a

number of NMR spectroscopic studies have

been carried out. These include conformational

studies of alkaloids using dynamic NMR, use of2H NMR in biosynthetic studies (with Nina

Rønsted), use of 31P NMR to characterise influ-

ence of ischemia upon composition of brain

phospholipids (with Harald Hansen, Department

of Pharmacology), use of pulsed-gradient spin-

echo NMR to characterise self-diffusion in phar-

maceutical microemulsion delivery systems (with

Mads Kreilgaard, Department of Pharmacy), and

conformational analysis of polar molecules is

aqueous solution (with Peter A. Nielsen and

Tommy Liljefors, Structural Chemistry). An exter-

nal grant will enable a deployment of state-of-

the-art 600 MHz NMR facilities and HPLC-MS-NMR equip-

ment during 2002.

(Jerzy W. Jaroszewski, Dan Stærk, Henrik Franzyk, Jette

Christensen, Hanne Ziegler, Majid Sairafianpour, Thomas

Høgh Jensen, Vicki Clausen, Bogdan Budnik [University of

Odense], Karim Bagherzadeh [Isfahan Research Centre of

Natural Resources, Iran], Henry Hägerstrand [Åbo Akademi

University], Carl Erik Olsen [Royal Veterinary and Agricultural

University], Ulla Wagner Smitt, Anne Adsersen and Henrik Toft

Simonsen [The Pharmacognosy Group], Partick Ekpe [Univer-

sity of Ghana], Lise Bolt Jørgensen [University of Copen-

hagen], Lars Hviid [Copenhagen University Hospital], Elin S.

Olafsdottir [University of Iceland], Hellen Oketch Rabah

[University of Nairobi]).

Synthesis of analogues of polyamine wasp toxins

Through the development of ligands with a potent and specif-

ic interaction with receptors it is possible to acquire knowl-

edge about the structure and function of the receptors even

in cases where the three-dimensional structure of the recep-

tor is not available. This applies to many membrane-bound

receptors in the central nervous system (CNS). A ligand-type

which is of our particular interest is the group of polyamine

spider and wasp toxins, which have been shown to be non-

competitive inhibitors of ion channel coupled glutamic acid

and acetylcholine receptors. In general these polyamine tox-

ins, called philanthotoxins, are built from three different sec-

tions (depicted below as sections 1-3): a polyamine moiety,

an amino acid, and an acyl moiety.


PAGE 58

NMR spectroscopy plays an important role in the research of the Department.

In a preliminary hypothetical model

for the binding of philanthotoxins

(see figure) it was suggested that

these compounds block the ion

channels due to an electrostatic

binding to ionized carboxylic acid

residues in the transmembrane por-

tion of the receptor, and via hy-

drophobic interactions of the amino

acid side chain and acyl chain with

the outer part of the receptor.

Polyamine toxins have been shown

to exhibit a protective effect on

nerve cells, and therefore are inter-

esting as leads in medicinal chem-

istry research towards treatment of

neurodegenerative diseases. It was

previously shown, that the polyamine

chain is essential for activity on glu-

tamate receptors, whereas the inner

amino functionalities may be omitted

in compounds interacting with

acetylcholin receptors.

The present research is concerned with the design and

synthesis of novel conformationally restricted apolar head

groups (i.e. sections 2 and 3). These are then used in parallel

solid-phase synthesis of compounds with improved biological

activity as compared to natural philanthotoxins. Also, novel

sequential solid-phase methods for synthesis of the poly-

amine part are being developed. Here the main effort is to

obtain polyamines, in which N-alkylated, �- or �-alkyl substi-

tuted amines have been incorporated. This requires develop-

ment and optimisation of novel synthetic methods, which

subsequently will allow a systematical study of structure-ac-

tivity relationships in much more diverse libraries of analogues

of polyamine toxins than those investigated previously. The

use of computational methods to correlate the structure of

the apolar head groups with the observed receptor affinity is

currently under consideration for future synthetic analogues.

The tests regarding receptor binding is currently performed in

co-operation with University of Nottingham, United Kingdom.

(Henrik Franzyk, Jerzy W. Jaroszewski, Malene Ryborg

Jørgensen, Christian Adam Olsen, Povl Krogsgaard-Larsen

[The Neuromedicinal Chemistry], Kristian Strømgaard

[Columbia University, New York], Kim Andersen [Lundbeck

A/S], Peter N. R. Usherwood and Ian Mellor [University of

Nottingham]).

Protein modelling and ligand design

by computational methods

By using a combination of computational methods the molec-

ular events associated with many biomolecular processes can

be studied. The availability of experimentally determined 3D-

structures of proteins and ligand-protein complexes makes it

possible to directly study the details of molecular recognition

and perform so-called structure-based computer-aided ligand

design. Even when the detailed structure of the receptor or

enzyme is not known, it is often possible by molecular mod-

elling to construct reliable three-dimensional models, which

allows important issues like activity, selectivity and resistance

to be studied. In cases where only pharmacological data for a

set of ligands are available, 3D-pharmacophore models and

3D-QSAR models which describe important requirements for

the interactions between the ligands and a particular receptor

or enzyme may be developed.

A number of enzymes and ligand-binding domains of re-

ceptors have been studied in order to identify the molecular

features responsible for affinity, selectivity and in some cases

also resistance. One of the enzymes we have studied is ma-

trix metalloproteinase (MMP). Human MMP’s have been found

to be involved in many different disease states, e.g. arthritis,

cancer and osteoporosis. In these diseases, an imbalance is

observed between the MMP’s and their natural inhibitors, and

accordingly, it is desirable to be able to selectively inhibit the

different MMP’s. Key differences have been identified between

several of these enzymes. New methods for selection of pos-

sible binding modes (conformations) and subsequent predic-

tion of their relative binding strength have been developed

based on multivariate statistics. These methods have been

extensively evaluated on a large and structurally diverse set of


PAGE 59

Computational methods are important in structure determination.

A substituted flavone fitted to a pharmacophore

model for the benzodiazepine site of the GABAA re-

ceptor. The pharmacophore model has been used

for the design of the compound which displays high

affinity for the receptor with a Ki value of 0.9 nM.

S1-S5 represent areas occupied by the receptor.

H1 and H2 are hydrogen bond donating receptors

sites, whereas A2 is a hydrogen bond accepting

site. L2 denotes a lipophilic cavity.

ligand-macromolecule complexes. The MMP project is carried

out in collaboration with Dr Inge Thøger Christensen, Novo

Nordisk A/S.

Studies on ligand-protein interactions have been performed

for two novel anti-cancer targets MetAP-2 (methionine

aminopeptidase) och VEGF (the vascular endothelial growth

factor) aiming at the design of new ligands which may be de-

veloped into anti-cancer drugs. These studies have been

done in collaboration with Leo Pharmaceuticals.

On the basis of the availability of three-dimensional struc-

tures for the ligand binding domain of an ionotropic glutamate

receptor (iGluR2) in complex with various ligands, a number

of studies have been performed aiming at an understanding

of subunit/subtype selectivity and the design of new

subunit/subtype selective ligands. These studies have in par-

ticular focused on the role of water molecules in the ligand

binding site for the ligand binding mode as well as for ligand

affinity and selectivity. Studies along these lines have also

been performed for metabotropic glutamate receptors on the

basis of the experimentally determined structure of the ligand-

binding part of the mGluR1 receptor. Collaborators in the glu-

tamate receptor projects have been Professor Arne Schousboe,

Department of Pharmacology, the Protein Crystallography and

the Neuromedicinal Chemistry Groups at the Department of

Medicinal Chemistry and Prof. Guiseppe Campiani, Siena,

Italy.

3D-pharmacophore models have successfully been used

for the design of novel high-affinity ligands for the GABA and

benzodiazepine sites of the GABAA receptor. Pharmacophore

models for subtypes of neurokinin receptors (NK1 and NK2)

have been developed and, addition, for all subtypes of the

�1-adrenoceptor. Ligand design on the basis of these models

have been initiated.

The pharmacophore model for the benzodiazepine site of

the GABAA receptor has been used for database searches

and a number of new interesting lead compounds have been

identified. These studies have been performed in collabora-

tion with H. Lundbeck A/S, NeuroSearch A/S, Dr Ingrid

Pettersson at Novo Nordisk A/S, Professor Olov Sterner,

University of Lund and Professor Mogens Nielsen.

(Tommy Liljefors, Anders Hogner, Jeremy Greenwood, Anne

Techau Jørgensen, Anders Poulsen, Thomas Balle, Gitte

Elgaard Terp, Marie-Louise Waagensen, Kasper Harpsøe,

Flemming Steen Jørgensen).

Pharmaceutically important physico-chemical properties

The oral bioavailability of a drug compound is an extremely

complex property influenced by factors like absorption, distri-

bution, metabolism and excretion (ADME properties).

Solubility is one of the key factors determining absorption,

and accordingly prediction of aqueous solubility has become

a major issue in the drug development process.

New models for prediction of aqueous solubility and several

other ADME properties have been developed and extensively

compared with models previously reported in the literature.

The purpose of these studies is to develop tools, which make

PAGE 60


Three-dimensional model of acetyl salicylic acid coloured according to

atom type. The water-accessible surface is shown as a semi-transparent

cloud around the molecule.

it possible to determine the ‘drug-likeness’ of compounds pri-

or to synthesis.

Solubility is influenced by solid phase properties, e.g.

molecular structure and crystal packing, as well as by exter-

nal factors like temperature, pH and ionic strength. The crys-

tal packing is a fine balance between many weak and

stronger intermolecular contacts, but unfortunately, crystal

structures are generally not predictable. Projects have been

undertaken in order to achieve improved understanding of the

relationships between solid phase properties such as solubili-

ty and compressibility on one side and the actual crystal

packing on the other side. A series of substituted benzoic

acid salts have been analysed in order to achieve insigth in

the effect of structural parameters on the formation of low

solubility salts, and a series of parabenes have been analysed

for the structural effect on elasticity and compressibility. The

ultimate goal is to be able to predict the solid phase proper-

ties and to design new compounds with optimal characteris-

tics.

These projects involve collaborations with Professor Claus

Selch Larsen at the Department of Analytical and

Pharmaceutical Chemistry, Professor Sven Frøkjær and

Professor Henning Gjelstrup Kristensen at the Department of

Pharmacy and Dr Inge Thøger Christensen, Novo Nordisk

A/S.

(Karla Frydenvang, Tommy Liljefors, Birthe Jensen, Jørgen

Bonefeld Kristensen, Flemming Steen Jørgensen).

Structural studies of CNS proteins by X-ray crystallography

An increased knowledge on three-dimensional structures of

proteins is necessary to fully understand their function at a

molecular level. The protein crystallography group is mainly

focusing on three types of CNS proteins: Ionotropic gluta-

mate receptors (iGluRs), neural cell adhesion molecule

(NCAM), and �-synuclein. iGluRs and NCAM are membrane-


PAGE 61

Water molecules in contact with the surface of crystalline urea.

X-ray structure of the ligand-binding domain of GluR2 in complex with the

agonist (S)-Thio-ATPA.

Crystallisation and evaluation of crystals

are fundamental steps in the structure

determination of proteins by X-ray

crystallography.

bound receptors involved in a series of important processes

within the central nervous system. �-synuclein is a brain pro-

tein, which plays a role in neurodegenerative diseases such

as Parkinsons and Alzheimers disease.

Within the glutamate receptor project, we have so far fo-

cused on the ligand-binding domain of GluR2 in complex with

different AMPA receptor agonists and antagonists. Several

structures of complexes have been determined providing a

wealth of information on ligand binding and receptor activa-

tion. The structures of GluR2 in complex with ligands show

different binding modes for the ligands and disclose domain

movements taking place upon ligand binding. Expression and

purification of other receptor subunits has been initiated to

address subtype selectivity.

In the NCAM project, it is our goal to stepwise build up the

whole extracellular part of the receptor by structure determi-

nations of fragments of NCAM, and to determine structures

of NCAM in complex with heterophilic binding partners. This

year, we determined the structure of NCAM-IgI-II-III, and the

structure has allowed us to put forward reliable models for

both NCAM cis and trans interactions, reflecting interactions

of molecules on the same cell and on opposed cells. NCAM-

IgI-II-III-IV has recently been crystallised, and co-crystals of

NCAM-IgI-II and sucroseoctasulphate have been obtained to

address the question whether homophilic and heparin binding

can occur simultaneously.

�-Synuclein is a 14 kDa protein, which belongs to a family

of natively unfolded proteins without, or with very little, sec-

ondary structure elements. Different crystallisation conditions

and various additives are being investigated in order to trigger

the protein, as well as two mutants thereof, to fold and crys-

tallise. Folding is probably triggered by binding to its biologi-

cal target, as well as by polymerisation (fiber formation).

In addition, the structures of three peptide nucleic acids

(PNAs) have been determined. PNA analogues are potential

antisense/antigene drugs. All projects are performed in col-

laboration with both national and international collaborators

from universities and industry.

(Anders Hogner, Christina Kasper, Jette Sandholm Kastrup,

Nikolaj Kulahin, Ingrid Kjøller Larsen, Marie-Louise Lunn,

Bettina Bryde Nielsen, Anja Kallesøe Pedersen, Britt

Petersson, Vladik Soroka, Lise Baadsgaard Sørensen).

GABAA receptor ligands and GABA uptake inhibitors

The GABAergic neurotransmitter system involves a number of

synaptic processes and mechanisms, which have been stud-

ied pharmacologically and constitute potential therapeutic tar-

gets. In continuation of previous projects in this field, the de-

sign and development of ligands for the GABAA receptor and

the GABA uptake system have been of primary interest.

The project on GABAA receptor ligands has been continued

in close collaboration with Professor Tommy Liljefors and his

group. According to a previously proposed pharmacophore

model for GABAA receptor agonists, a receptor cavity in the

vicinity of the 4-position of the 3-isoxazolol ring in 4-PIOL, a

low-efficacy partial GABAA agonist, exists. To explore the di-

mensions and other properties of the receptor cavity, a num-

ber of analogues of 4-PIOL, in which the 4-position of the 3-

isoxazolol ring is substituted by different groups, has been

synthesised. This study has transformed 4-PIOL into the

PAGE 62


highly potent GABAA antagonist 1. During the past year, 1

has been developed into a series of very potent GABAA an-

tagonist including compound 2, which in functional assays is

even more effective than 1.

Similar structural changes have been made for the isothia-

zolol analogue of 4-PIOL, thio-4-PIOL, which has been shown

to possess markedly higher efficacy than 4-PIOL. Although

the chemistry of 3-isothiazolols is complex, a series of thio-4-

PIOL analogues has been synthesised and shown to be sig-

nificantly more potent than the 3-isoxazolol analogues.

In collaboration with professor Arne Schousboe and his

group at the Department of Pharmacology a number of very

significant and, from a therapheutic point of view, potentially

important results on the GABA uptake project have been ob-

tained. The cyclic amino acid, nipecotic acid, was discovered

by the NeMe group as a specific GABA uptake inhibitor some

years ago and subsequently converted into the antiepileptic

drug, tiagabine, by incorporation of the lipophilic DTB group

as an N-substituent at Novo Nordisk A/S. In the NeMe group

N-Me-exo-THPO was subsequently syn-

thesised and shown to be a glia-selective

GABA uptake inhibitor. The DTB-ana-

logue of N-Me-exo-THPO has now been

fully characterised as a very potent GABA

uptake inhibitor showing a unique phar-

macological profile different from that of

tiagabine. Due to a very complex chem-

istry required for the synthesis there has

been no further development of this com-

pound.

Very recently the isomeric amino acids

3 and 4 have been shown to have weak

GABA uptake inhibitor effect. By introduc-

tion of lipophilic substituents, both 3 and 4 were converted

into GABA uptake inhibitors showing yet another unique

pharmacological profile. This effect of the analogues of 3 and

4 is now under further exploration in animal behavioural stud-

ies in order to elucidate their therapeutic potential.

The projects described are interdisciplinary collaboratory

projects involving other research groups at DFH and in the

industry.

(Titi Akinleminu, Rasmus Prætorius Clausen, Bente Frølund,

Karla Frydenvang, Povl Krogsgaard-Larsen, Christian

Madsen, Lotte Olsen, Dorte Seir Petersen, Tine Bryan

Stensbøl).

Excitatory amino acid receptor ligands

The central excitatory amino acid neurotransmitter, glutamic

acid (Glu), operates through a large number of receptor sub-

types divided into two groups, the ionotropic (iGlu) receptors

and the metabotropic receptors, the latter group belonging to

the superfamily of 7-TM receptors. The iGlu receptors com-

prise the NMDA, the AMPA (GluR1–4), and the kainic acid

(GluR5–7 and KA1–2) receptors. In recent years the research

has been focused on the AMPA and kainic acid subgroups of

receptors.

During the past one year period a num-

ber of research projects related to

bioisoster replacement of carboxy groups

have been accomplished. As part of an

ongoing project using 3-isoxazolols as

carboxy group bioisosteres, new ana-

logues of AMPA containing aromatic sub-

stituents in the 5-position of the 3-isoxa-

zolol ring, exemplified by the pyrazinyl

analogue (1), have been synthesized in an

effort to further map out structural re-

quirements for AMPA receptor agonist

activity. In connection with these studies,

a new and versatile method for the


PAGE 63

Proposed bioactive conformation of 1 placed in a pharmacophore model

for GABAA agonists . The tetrahedron indicate areas occupied by the

receptor.

Nipecotic acid

Thio-4-PIOL4-PIOL

1 2

DTB-N-Methyl-exo-THPON-Methyl-exo-THPO

3 4

preparation of 5-substituted 3-isoxazolols via acylated

Meldrum’s acids has been developed.

In another project 1-hydroxyazole-containing �-amino acids

have been synthesised and pharmacologically evaluated.

These studies have identified the 1-hydroxypyrazole (2a and

2b) and the 1-hydroxy-1,2,3-triazole (3a and 3b) analogues

as new and useful bioisosteres at iGlu receptors and at Glu

transporters. Molecular modelling studies using a published

crystal structure of the ligand binding site of GluR2 have

shown that these compounds can bind to the receptor in an

“AMPA-like mode” making the same favorable contacts as

AMPA and not entering sterically forbidden zones.

Important progress has also been achieved in projects us-

ing the 3-isothiazolol ring system as a carboxy group

bioisostere at Glu receptors. In this regard regioselective lithi-

ation and functionalisation of 3-(benzyloxy)isothiazole has

been carefully investigated, and these studies has led to the

preparation of thioibotenic acid, the sulfur analogue of the

neurotoxic natural product ibotenic acid. The pharmacological

characterisation of thioibotenic acid carried out so far shows

interesting agonist activity at iGlu as well as mGlu receptors.

The 3-hydroxy-1,2,5-thiadiazole ring system, which forms

the distal acidic part of the �-amino acid TDPA, is structurally

closely related to the 3-isothiazolol ring present in thioibotenic

acid. Pharmacological studies on the enantiomers of TDPA

have revealed a complex and interesting pharmacological

profile. In addition to a moderate agonist activity at group I

mGlu receptors, (S)-TDPA selectively interacts with the Glu

transporter EAAT2, and shows agonist activity at AMPA re-

ceptors. In contrast, (R)-TDPA shows a more clear pharma-

cology, being a selective AMPA receptor agonist

with almost the same affinity as (S)-TDPA. The

transporter activity and the unusually low stereose-

lectivity at AMPA receptors observed for TDPA

makes the 3-hydroxy-1,2,5-thiadiazole a unique

carboxy group bioisostere.

ACPA and its demethyl analogue, which are ana-

logues of AMPA, have been resolved using chiral

HPLC. X-ray crystrallography has been used to es-

tablish the absolute configuration of the resolved

enantiomers. The configurational assignment ob-

tained from this X-ray study has been supplement-

ed by an asymmetric synthesis of (S)-ACPA and an

X-ray analysis of a derivative of (S)-ACPA.

Pharmacological studies have revealed that the po-

tent AMPA receptor agonist activity of ACPA resides

exclusively in the S-enantiomer, and that both

enantiomers of demethyl-ACPA are relatively weak

AMPA receptor agonists, (S)-demethyl-ACPA being

the most potent.

In continuation of ongoing projects, the crystal

structures of the potent GluR5 receptor agonists,


Chemical structure of selected ionotropic Glu receptor ligands.

PAGE 64

Compound 3b docked into the binding site of GluR2. Selected hydrogen bonds are shown in black.

ATPA and thio-ATPA, have been solved. Together with quan-

tum chemical calculations these studies show, that whilst the

3-isoxazolol tautomer of ATPA predominates in all phases, the

3(2H)-isothiazolone tautomer of thio-ATPA predominates in

the crystal structure and most likely in weakly acidic aqueous

solution.

Furthermore, hybrid analogues of the kainic acid receptor

agonists (2S,4R)-4-methyl-Glu and ATPA (exemplified by 4)

have been prepared and show highly selective GluR5 recep-

tor affinity.

Many of the mentioned projects have been performed in

close collaboration with other research groups at the Royal

Danish School of Pharmacy, in particular structural chemists

and molecular pharmacologists and other research groups in


(Hans Bräuner-Osborne, Lotte Brehm, Lennart Bunch,

Rasmus P. Clausen, Bente Frølund, Karla Frydenvang, Mette

Guldbrandt, Mette B. Hermit, Tommy Nørskov Johansen, Povl

Krogsgaard-Larsen, Ulf Madsen, Birgitte Nielsen, Frank Sløk,

Tine B. Stensbøl, Ulrik Svane Sørensen, Jón Valgeirsson,

Stine B. Vogensen).

Family C 7TM receptors

Human G-protein coupled receptors are

generally divided into three families

(Family A, B and C) based on their re-

semblance in amino acid sequence. All

G-protein coupled receptors span the

cell membrane seven times and are

thus also called 7 transmembrane

(7TM) receptors. Family C, which con-

sists of eight glutamate (mGlu1-8), two

GABAB and one calcium-sensing (CaR)

receptor, has traditionally been charac-

terised by a unusually large amino-

terminal ligand binding domain (see

figure).

The NeMe group has developed

pharmacological assay for the mGlu,

GABAB and CaR receptors that enable

us to study compounds synthesised in

the NeMe group and by collaborators.

In this way new potent ligands have

been developed which display selecti-

vity for subsets or individual receptor

subtypes.

Based on mutational studies we have

been able to identify amino acids in the amino terminal domain,

which are directly involved in agonist binding. The recent pub-

lication of the X-ray crystal structure of the ligand binding do-

main of the mGlu1 receptor has led us to generate computer

models of the remaining seven mGlu receptors. These models


Model of the extracellular ligand binding domain of a metabotropic gluta-

mate receptor complexed with glutamate.

Single crystal of (S)-demethyl-ACPA used in the X-ray analysis together

with a perspective drawing of the molecule based on the analysis.

PAGE 65

are being tested by mutagenesis with the aim of increasing

our understanding of ligand selectivity.

Numerous studies have shown that the family C receptors

are homo- or heterodimers. Based on the X-ray crystal struc-

ture it has been proposed that agonist binding leads to acti-

vation by bringing the two 7TM domains in the dimer closer

together. This hypothesis has been tested by use of a tech-

nique called bioluminescence resonance energy transfer

(BRET).

The NeMe group has recently cloned a new group of previ-

ously unknown family C receptors. In contrast to previous as-

signed family C members, this new group is characterised by

a short amino terminal domain. The expression pattern and

cellular localisation of the new receptors has been determined

(see figure). 1000 putative ligands have been screened in a

FLIPR high-throughput assay, but unfortunately no active lig-

ands have yet been identified.

(Hans Bräuner-Osborne, Anders A. Jensen, Mette B. Hermit,

Petrine Wellendorph).

New synthetic methodologies

The synthesis group has been working on several new syn-

thetic methods of importance in medicinal chemistry. Regio-

selective introduction of functional substituents and cross-

couplings have been performed with complete control in all

positions in 1-hydroxypyrazole and pyrazole. The reactions

have been combined with new anionic cyclisation reactions

which have provided several new ring systems and ring sys-

tems of significant interest in medicinal chemistry. Similar re-

actions have been performed in the imidazole and thiophene

series.

Effective methods for the preparation of 2-substituted

phenylboronic esters have been developed. These com-

pounds serve as synthons and have a enormous potential in

synthesis and medicinal chemistry allowing connection of two

functional aryl groups and construction of rings by anionic

cyclisation.

Cross-coupling reactions have also been employed by the

construction of tamoxifen analogues with improved proper-

ties. Subsequent anionic cyclisation have given a highly active

analogue with constricted conformation.

A broafly applicable synthon for preparation of phenyl-

glycines and heterocyclic analogues has been developed and

its versatility demonstrated by preparation of a series of new

or difficult accessible amino acids. A protocol for preparation

of heterocyclic phenyl analogues has also been established.

Several of the new compounds are under biological testing.

New drug substances have been coupled

to peptide carriers in order to improve the

transport of the drug through the intestinal

barrier. New methods for construction of li-

braries of privileged structures using solid

phase chemistry have been initiated.

New methods for isotop labeling of drug

metabolites and positron emitting drug

tracers are under development.

Development of methods for preparation of

lipid conjugates for drug targeting is in pro-

gress.

(Mikael Begtrup, Patrizia Cali, Peter Elm,

Jørgen Eskildsen, Jesper Kristensen, Uffe

Larsen, Jan Pawlas, Rune Severinsen,

Martin Wenckens, Niels Østergaard og Per

Vedsø).


Confocal mi-

croscopy image of

cells expressing an

orphan 7TM recep-

tor fused to green

fluorescent protein

(GFP).

PAGE 66


PAGE 67

Department ofPharmaceutics

SPHERE OF INTEREST

The Department of Pharmaceutics deals with the formulation,

processing and quality assurance of drug products, i.e. the

objectives involved in bringing a drug substance into an effec-

tive and safe dosage form. Further, the activities include how

to administer the drug product safely and optimise the effect

for the individual patient. The scientific and teaching objec-

tives are therefore dosage form design, processing of dosage

forms, quality assurance, clinical pharmacy and pharmaco-

therapy.

The formulation design of drug products takes its starting

point in the chemical, physico-chemical, pharmacokinetic and

pharmacodynamic properties of the drug substance, the

route of administration and the manufacturing method. The

stability of the substance as such and in formulation, the

choice of excipients and different approaches to overcome

the transport across restrictive biological barriers are objects

of interest. Chemical, physical and pharmaceutical-technical

methods for evaluation of drug formulations are necessary

tools.

The Department participates in an extramural research cen-

tre, the Centre for Drug Design and Transport. Professor Sven

Frøkjær is the head of the centre, established as a four-year

programme to be terminated on 1 November 2001.

Professor Henning G. Kristensen is chairman of the European

Pharmacopoeia Commission, which is important to the func-

tioning and development of the Department.

RESEARCH

The four main areas of research at the Department of

Pharmaceutics are:

Pharmaceutical formulation: Formulation of drug products

taking into consideration the physical, chemical and pharma-

cokinetic and pharmacodynamic properties of the drug sub-

stance, the route of administration, the processing method

and clinical use of the product


Head of Department:

Associate professor Margrethe Rømer Rassing, PhD, MSc (pharm.)

PAGE 68

Civil servants from The Ministry of Education and The Ministry

of Research visited the department in November 2000.

Drug delivery: Design of drug delivery systems actively con-

trolling and optimising the absorption of drug substance

and/or its transport in the living organism to the site of action

Processing technology: Unit operations applied in the pro-

cessing of drug products and the influence of the method

selected on formulation design

Clinical pharmacy: Optimisation of the therapeutic result of a

medication taking into consideration the biopharmaceutical

profile of the drug product and its pharmacokinetic and phar-

macodynamic properties

The character of the research is interdisciplinary and integrat-

ed. Projects are typically carried out in research groups of

scientists from various research groups established at the

Department of Pharmaceutics and from other university de-

partments, university hospitals and hospital pharmacies and


The number of PhD students at the Department has grown

steadily in recent years. In 2001 approximately 35 PhD stu-

dents were supervised by staff members of the Department

of Pharmaceutics in collaboration with supervisors from the

pharmaceutical industry. The involvement of adjunct profes-

sors is very important in this context. At present adjunct pro-

fessors are managing director Ole Wørts, Glatt Norden, Dr.

Vagn Handlos, head of the State University Hospital Pharmacy,

Professor Dr. Gert Storm from the University of Utrecht in the

Netherlands and Professor, Dr. Hans Lennernäs, Uppsala

University, Sweden. Professor, Dr. Hans Peter Merkle, ETH

Zurich, Switzerland, has been appointed adjunct professor in

2001.

The bulk of PhD scholarships are based on external fund-

ing, in particular from the Danish pharmaceutical industry in

keeping with contracts established on drug formulation train-

ing and the Centre for Drug Design and Transport. The

agreed industrial funding is, however, running out. The num-

ber of PhD students will therefore decline dramatically during

the next two years unless we are able to attract new funding.

The strategy of the Department of Pharmaceutics is to

strengthen international relations by exchanging PhD stu-

dents and staff members with university departments abroad.

Consequently nearly all PhD students visit university depart-

ments abroad as part of their PhD programme. The Depart-

ment also attaches great importance to hosting foreign PhD

students and scientists to establish collaborative research.

PHARMACEUTICAL FORMULATION

The formulation of low soluble drug substances intended for

oral delivery has been subject to intensive research in recent

years. Current projects focus on the effects of luminal liquids

on the dissolution/solubilisation of drug substances, lymphatic

transport of lipophilic substances and formulation of lipid-

based drug delivery systems. The research is conducted in

collaboration with the Danish pharmaceutical companies,

Dumex Alpharma A/S, Leo Pharmaceuticals A/S and H.

Lundbeck A/S, as well as with scientists at universities

abroad. A new research consortium within the Øresund re-

gion was established in 2001. The Department participates in

a project on in vivo in vitro correlations of lipid-based formula-

tions. External partners are Lund University, Sweden, Camu-

rus, Sweden, AstraZeneca R&D Lund, Sweden and Nycomed

Pharma, Denmark.

In vitro methods suitable for the screening of drug sub-

stances and their formulations have been established on the

basis of aqueous media simulating the compositions of the

gastro-intestinal liquids in fasted and fed states. Further, a

lipolysis model for dissolution testing and evaluation of effects

of fat-enriched diet on oral absorption has been established.

The model is subject to evaluation in collaboration with Aventis

Pharma, Frankfurt. An increasing number of new drug sub-

stances are highly lipophilic and thus prone to lymphatic

DEPARTMENT OF PHARMACEUTICS

The attachment of adjunct professors has become very important. Dr. Hans Lennernäs, Uppsala

University was appointed in September 2000.

PAGE 69

transport. Animal models (rats, dogs) for studies of lymphatic

transport have been established and applied in investigations

on the role of triglycerides in systemic absorption.

Investigations on lipid-based formulations, which were con-

cluded in 2001, concern the development of dry emulsions

and SEDDS for oral delivery of low soluble drugs and the use

of tocopherols as a vehicle for low soluble drugs.

Lipid-based formulations for parenteral use are also subject

to research. The projects concern the role of structured lipids

in parenteral drug delivery and emulsion technology. The aim

is to investigate the possibilities of incorporating hydrophilic

as well as lipophilic drug substances into the lipid-based vehi-

cles.

Particulate drug delivery systems are the subject of two

projects carried out in collaboration with Cheminova and

Pharmexa.

DRUG DELIVERY

The research within the area of Drug Delivery is focused on

drug transport across biological membranes and studies on

lipid-based drug delivery systems.

Macromolecules such as peptides, proteins, and oligonu-

cleotides present a unique pharmaceutical formulation chal-

lenge. The therapeutic application of these groups of com-

pounds is limited by several problems, such as lack of physi-

cal and chemical stability and the lack of optimal physico-

chemical properties for adequate transport across biomem-

branes. Thus, the pharmaceutical sciences face the challenge

of gaining a more basic understanding of transport problems

and developing strategies to solve them.

Access to well-characterized in vitro models to study drug

transport across biological membranes is of the utmost im-

portance. Various models based on tissue as well as cell cul-

ture models are established in the Department, i.e. intestinal,

buccal, and nasal membranes, cornea, and skin, the human

colon cell line, Caco-2, and the human buccal cell line, TR

146. These in vitro models are important tools for obtaining a

more fundamental understanding of the molecular and phar-

maceutical parameters, which are of significance for drug

transport across biological membranes. However, in some

situations the findings from in vitro studies have to be con-

firmed in vivo in order to establish biological relevance. These

studies are usually conducted on mice, rats, or rabbits.

To obtain effective drug therapy, the drug substance must

be able to reach the site of action in a therapeutically active

concentration. Various approaches are taken to optimise the

drug delivery properties of drugs to improve membrane trans-

port and release characteristics. Combining bioreversible

derivation with carrier-mediated transportation has developed

the classic prodrug approach further. Within this area, the

Department is focusing on the potential use of the di-/tripep-

tid carrier as a transporter for drugs with poor membrane

transport characteristics. This research is being conducted in

collaboration with the Department of Medicinal Chemistry.

The development of particulate drug delivery systems

based on liposome technology is also a focus area. These

activities are carried out in collaboration with Professor O. G.

Mouritsen, the MEMPHYS-group, Department of Physics,

University of Southern Denmark.

As more therapeutic proteins are made available, it is es-

sential to formulate these drugs into safe, stable and effica-

cious delivery systems. Our research goal in this area is to

obtain a basic understanding of parameters controlling the

physical stability of proteins in pharmaceutical systems, pri-

marily by investigating the effect of excipients and studying

protein-interface interactions. A Protein Formulation Network

has recently been established in collaboration with a number

of Danish pharmaceutical companies.

In the area of oligonucleotide/DNA drug delivery, the aim is

to develop polymeric and lipid-based drug delivery systems

that can effectively deliver oligonuleotides or plasmid DNA to

the target site. The therapeutic focus within this area is gene

and antisense therapy as well as DNA vaccination.

PROCESSING TECHNOLOGY

The research within processing technology focuses on the

formulation and processing of solid dosage forms intended

for oral administration. Central themes are particle technology,

unit operations and pharmaceutical preformulation. Particle

agglomeration has long been a major research field. The re-

search group is well equipped with various types of mixer-

granulators. Current research concerns melt granulation and

melt pelletisation in high shear mixers, in particular the role of

binder viscosity for the formation and growth of agglomerates.

Other projects deal with the use of melt agglomeration for de-

veloping matrix pellets with predictable dissolution properties,

e.g. the use of solid dispersion technique to increase the dis-

solution rate of low soluble drugs. This research is conducted

in collaboration with Danish pharmaceutical companies, in

particular H. Lundbeck A/S.

Pelletization in rotor-fluidised beds is studied to develop

rapidly disintegrating pellets. The project is conducted in col-

laboration with Glatt Norden and Professor P. Kleinebudde,

University of Halle, Germany.

Compaction of particulate solids into tablets has been the

subject of studies on mathematical modelling. This experi-

mental work is based on the use of a compaction simulator.

Finally, the research group has established research on the

atomisation of aqueous solutions with a view to coating fine

particles and the preparation of inhalable particles. The use of

effervescent atomisation in combination with spray drying is

being investigated with a view to the design of the atomizer.

PAGE 70


At a later stage the research will be re-directed towards the

coating of fine particles. Investigations on the preparation of

inhalable particles are being made in collaboration with

AstraZeneca Lund R&D and the University of Lund, Sweden.

CLINICAL PHARMACY

Clinical pharmacy deals with rational pharmacotherapy and

optimising the clinical use of drugs. The main research areas

for the Clinical Pharmacy group concern indicators to evalu-

ate the drug dosing-response relationship, and drug monitor-

ing by clinical pharmacokinetic service. Pain management is

one of the main areas of interests for the group. Opioids are

studied in patients with chronic pain of malignant as well as

non-malignant origin. Paracetamol and other non-steroid anti-

inflammatory drugs (NSAIDs) are studied in patients with

acute pain, children as well as adults. The pharmacokinetics

of prenisolone in the acute phase of the treatment of children

diagnosed with acute lymphoblastic leukemia is another re-

search area of great interest. The group is often involved in

projects concerning the influence of drug formulation and de-

vices on patient compliance and acceptance.

CENTRE FOR DRUG DESIGN AND TRANSPORT

The "Centre for Drug Design and Transport" is an extramural

research centre established in November 1997 as a four-year

programme and therefore terminated in October 2001.

The centre is based on seven Danish research groups and

funded by the Danish Medical Research Council, several

Danish pharmaceutical companies and the participating aca-

demic institutions. Professor Sven Frøkjær is the head of the

centre. See page 26 Research Centres at The Royal Danish

School of Pharmacy.

TEACHING

During the summer of 2001, a major renovation of the De-

partment was finalised and the amount of square meters in-

creased to provide better teaching and research facilities. The

new conditions are very much appreciated by staff and stu-

dents alike.

In the academic year 2000/2001, the Department taught

the introduction to the study of pharmacy, compulsory and

optional courses in pharmacy, supervised students doing their

master’s theses and held PhD courses.

The introduction to the study deals with lectures and tutori-

als in drug formulation and manufacturing and knowledge of

the European Pharmacopoia. Further, demonstrations in how

to prepare e.g. tablets and parenteralia are given.

Students are trained to master drug formulation, drug pro-

duction and evaluation as well as quality assurance. The

compulsory courses combine lectures, tutorials, laboratory

work, written exercises and oral presentations. During the

fourth year of the programme, students carry out a project

within drug formulation and one within drug manufacturing.

The content of the course in drug formulation was revised in

2001, and a different textbook used (Physicochemical Prin-

ciples of Pharmacy). A project entitled "Test of an examination

form for better evaluation of the students’ understanding and

ability to solve more complex pharmaceutical problems" has

been planned and will be carried out in the spring 2002.

Furthermore, the Department of Pharmacy together with the

Department of Pharmacology held a compulsory course in

pharmacotherapy.

The Department also offered elective courses in advanced

drug formulation, industrial production and quality assurance

of pharmaceuticals, validation in the manufacture of pharma-

ceuticals, controlled release, clinical pharmacy, statistical de-

sign of experiments, registration of drugs and seminars and

clinical practice in clinical pharmacy.

The two PhD courses dealt with drug delivery and clinical

evaluation of drug products, respectively. Furthermore, the


PAGE 71

Department made contributions to other PhD courses, e.g.

biological membranes, permeation barriers and drug target-

ing.

The Department of Pharmaceutics supervised 77 students

earning their master’s theses. About half of these students

worked on their theses at national or international pharma-

ceutical production sites or institutes. A number of foreign

students prepared their theses at the Department.

During the past three years, 18 students received their PhD

degree from the Department. Fifteen of the projects in the

field of drug formulation were funded by Danish pharmaceuti-

cal companies, the Danish Research Academy and the

Danish Medical Research Council through the Centre for Drug

Design and Transport. This programme has now been termi-

nated and unfortunately the number of PhD students at the

Department is decreasing. However, 34 people were regis-

tered for the PhD degree programme on 1 January 2002.

SPECIALISATION IN HOSPITAL PHARMACY

The need for specialised training in Hospital Pharmacy has

been acknowledged for several years. To improve the clinical

and scientific skills of hospital pharmacists, the Danish

Society of Hospital Pharmacy Managers in co-operation with

the Royal Danish School of Pharmacy are preparing a new

postgraduate programme. The new programme will focus on

clinical pharmacy –the optimal use of drugs for the benefit of

each patient and society. The curriculum will be

equivalent to one year of courses, although it will

be taught over a longer period of time.

Janne Rømsing, Department of Pharmaceutics, is

head of the Study Board for "Specialisation in

Hospital Pharmacy".

GUESTS AND EVENTS:

Professor Hans P. Merkle, Galenische Pharmazie

ETH, Zürich, has been attached to the department

as assigned professor.

Professor Gert Storm, Department of

Pharmaceutics, Utrecht University, The

Netherlands.

Professor Hans Lennernäs, Department of

Pharmaceutics, University of Uppsala, Sweden.

Dr. Thomas Abberger, University of Innsbruck,

Austria, joined the agglomeration research group

from August 13 to September 7 2001.

David Ilardia, PhD student at the university in

Vittoria, Spain, joined the GISOL research group

from January to July 2001.

Regina Westmeyer, pharmacy student at the uni-

versity in Kiel, Germany, joined the research on par-

ticulate DNA-formulations for a 6 months period from Sep-

tember 2001.

Christina Jimenez, MSc, Barcelona, has joined the GISOL-

group since October 1, 2001.

Minisymposium - NeuroScience PharmaBiotes and Drug

Design and Transport, March 1-2, 2001, Sorø

ADME in Drug Research - Tools for Evaluation and

Prediction of Absorption, Distribution, Metabolism and

Excreation, The Royal Danish School of Pharmacy, June 21,

2001.

World Conference on Drug Absorption and Drug Delivery,

June 18-20, 2001, Copenhagen, Co-chairman: Sven Frøkjær.

Member of the Scientific Programme Committee: Henning G.

Kristensen, Sven Frøkjær

Benzon Symposium - Drug Metabolism: Regulation and

Importance, September 16-20, 2001, Copenhagen.

Member of the organizing committee: Sven Frøkjær


Henning Gjelstrup Kristensen is a member of the Academy

for Technical Sciences (ATV), chairman of the Danish

Pharmacopoeia Commission and chairman for its sub-com-

mittee on Pharmacy. In 2001 he was elected chairman of the

European Pharmacopoeia Commission for a period of three

years. He is chairman of the Group of Experts No. 12 (Drug

Dosage Forms) and has the chair for a number of Working


PAGE 72

Parties settled under the Pharmacopoeia Commission:

Standard Terms, Powder Characterisation, Inhalations, Water

Qualities, and Methods for the manufacture of sterile prod-

ucts. In 2001 he became a member of the Steering

Committee for the Certification of Suitability of Drug

Substances. Member of WG4 on Dissolution and

Bioequivalence under FIP. Member of WHO Advisory Panel on

Pharmaceuticals. Referee within natural sciences and tech-

nology for the Research Council of Norway. Member of the

editorial board for International Journal of Pharmaceutics.

Member of the scientific board for Viikki Drug Research

Technology Center, University of Helsinki. From 2001,

Sectional Editor of the European Journal of Pharmaceutical

Sciences. He is a member of the scientific committee for the

4th World Meeting on Pharmaceutics, Biopharmaceutics and

Pharmaceutical Technology 2002, the Drug Absorption

Conference, EUFEBS 2001 and the EUFEBS Decennial

Anniversary Conference on Optimising Drug Development,

2001. In 2001 external examiner to assist the peer review of

Schools of Pharmacy in the United Kingdom and a member

of an international panel to review the research at the Faculty

of Pharmacy and Faculty of Medicine, University of Kuopio,

Finland.

Sven Frøkjær is a member of the Danish Academy for

Technical Sciences (ATV), trustee of the Alfred Benzon

Foundation, member of the Danish Medical Research

Council, member of the council for Centre for Advanced Food

Studies (LMC) and other program committees under the

Danish Research Agency, and board member of the

Biopharmaceutical Section, the Danish Pharmaceutical

Society. He is also a member of the Danish Pharmacopoeia

Commission and its subcommittee on pharmacy, and the

Drug Registration Committee under the Danish Medicine

Agency. He serves as member of the editorial board for

Pharmaceutical Research and STP Pharma Sciences and he

is section editor on European Journal of Pharmaceutical

Sciences

Mette Rasmussen is chairman of the Section of Clinical

Pharmacy, The Pharmaceutical Society of Denmark.

Lona Christrup is chairman of the Danish Pain Society

Margrethe Rømer Rassing has been pharmaceutical editor

of the Danish Drug Catalogue (Lægemiddelkataloget) until

September 1 2001.


Jette Jacobsen has received DKK 10.000 from

Generalkonsul Ludvig Tegner og Hustrus Mindelegat for

analytical equipment.

Hanne Mørck Nielsen has received a grant from the Alfred

Benzon Foundation for a post doctoral stay at ETH Zürich,

Switzerland.

Heidi Ugelstad Eirheim has received DKK 8.000 from Kong

Chr. X´s Fond for analytical equipment.

Sven Frøkjær is centre director of a four-year grant “Centre

for Drug Design and Transport” (1997-2001) from the Danish

Medical Research Council, in total DKK 32,000,000. In

2001, DKK 770,000 is used for research on pharmaceutical

formulation of slightly soluble drugs and DKK 1,500,000 for

research on membrane transport and drug delivery systems.

The Alfred Benzon Foundation has granted Sven Frøkjær

DKK 445,000 to an Investigator Fellowship for Dr. Marco van

de Weert, Utrecht University.

Furthermore, Sven Frøkjær obtained DKK 200,000 form the

Alfred Benzon Foundation, DKK 200,000 from Novo

Nordisk A/S, DKK 50,000 from Pharmexa A/S, DKK120,000

from Lica Pharmaceutical A/S and DKK 392,000 from

“Apotekerfonden af 1991”. He has also obtained funding for

a PhD student from Øresundskonsortiet “Explorative Drug

Formulations” partly supported by Erhvervsfremmestyrelsen

and Vinnova from Sweden.

Birger Brodin was donated DDK 110.000 from The

Carlsberg Foundation to partly finance research chemicals.

Bente Steffansen was donated DDK 458.000 from Leo

Pharmaceuticals A/S to partly finance a PhD program.

Bente Steffansen was donated DDK 112.000 from Zealand

Pharmaceuticals A/S to finance the salary to a research as-

sistant.

Bente Steffansen was donated DDK 500.000 from The

Danish Research Academy to the project “Application of the

human intestinal peptide transporter as an absorption promo-

tor for compounds with poor bioavailability”.

Anne Engelbrecht Thomsen was donated DDK 6,300 for trav-

elling expenses from Knud Højgaards foundation.

Anne Engelbrecht Thomsen was donated DDK 6,400 for trav-

elling expenses from the Study Foundation The Danish

Pharmacy Union.

Birger Brodin and Carsten Uhd Nielsen were donated by DDK

7,000 for travelling expenses from The Scandinavian

Physiology Society Foundation.

PROJECTS

PHARMACEUTICAL FORMULATION/PROCESSING

TECHNOLOGY

Design of oral formulations by pelletization techniques

High shear mixers and a conventional as well as a rotary flu-

idised bed are applied for pelletization of powders.

Hydrophilic and hydrophobic meltable binders and aqueous

binder solutions are applied as binder liquids. The effects of

the physical and physicochemical properties of raw materials

and binders and the effects of process variables on the prop-

erties of the final pellets, e.g. porosity, disintegration and dis-


PAGE 73

solution, are investigated. These studies are the basis of the

design of pellets with a modified drug release including pro-

longed release formulations, gastro-resistant formulations,

and colon specific delivery systems as well as pellets contain-

ing solid dispersions.

(Torben Schæfer, Helle Eliasen, Anita Johansen, Jakob

Kristensen, Anette Seo, Ole Wørts, Henning Gjelstrup

Kristensen, Per Holm, H. Lundbeck A/S, and Peter

Kleinebudde, University of Halle).

Absorption enhancing solid dosage forms

Different formulation principles and production techniques

that might be applicable for enhancing the oral absorption of

low soluble drugs have been screened. At the present time,

the preparation of dry emulsions by means of spray drying is

investigated. Different drug substances will be included in the

formulations, and the physical stability and the oral bioavail-

ability of the formulations will be tested.

(Tue Hansen, Per Holm, Kirsten Schultz, H. Lundbeck A/S,

and Torben Schæfer).

Microencapsulation by atomization techniques

The aim of the project is the encapsulation of solid particles

with polymers in order to modify and control the dissolution

rate of the solid. The project has, so far, dealt with the atom-

ization of polymer solutions using an effervescent atomizer.

The design of the atomizer has been optimized for spray dry-

ing processes. The studies shows that effervescent atomiza-

tion has some advantages compared to other atomization

methods: Reduced air comsumption, atomization of viscous

liquids and the possibility to produce small droplets.

(Frederik Pedersen, Torben Schæfer, Ole Wørts, Henning

Gjelstrup Kristensen)

Inhalable particles

The use of spray drying technology for the preparation of in-

halable particles is investigated in a project performed in a

collaboration with Lunds University and AstraZeneca R&D

Lund. The purpose of the project is to investigate and opti-

mise the physical stability of spray dryed powders with parti-

cle sizes in the range below 5 �m. Based on an investigation

on a series of carbohydrates it has been demonstrated that

the glass transitions temperature of the amorphous carbohy-

drate affects the crystallinity of the spray dried products. The

current studies focuses upon the possibilities to control the

crystallinity of spray dried particles.

(Kristina Ståhl, Anders Axelsson, Lunds University, Kjell

Bäckström, AstraZeneca R&D Lund, Torben Schæfer and

Henning G. Kristensen)

Formulation of nebuliser liquids

The aim of the project is to formulate solutions of antibiotics,

which are deliverable to the airways and lungs for the treat-

ment of infections by fungi. So far, the project has been con-

cerned about the development of an in vitro model to simu-

late the deposition of the antibiotic in the airways. Various

nebulisers are investigated. The model will be used to evalu-

ate formulated solutions and suspensions.

(Kenneth Manby Pedersen, Vagn Handlos and Lars Heslet,

State University Hospital)

Evaluation of the compression and

compaction characteristics of powders

The project includes a critical evaluation of the Heckel and

Walker equations and their ability to describe the compress-

ibility of powders. A model for description of compactibility

(the ability of a powder to cohere into or to form a compact)

and the lamination tendency is investigated through combina-

tion of the elastic properties under pressure and the Walker

coefficients of plastic deformation. The statistical distribution

of crushing strength of tablets has been investigated and

confirmed the hypothesis that the data followed a standard

normal distribution rather than the general accepted Weibull

distribution.

(Jørn Møller-Sonnergaard, Henning Gjelstrup Kristensen)

Critical compaction characteristics of pellets

and excipients with impact on the physical stability

of polymer membranes.

The release of drug from Modified-release tablets formulated

with filmcoated pellets (polydepot) are controlled by the poly-

mer membrane. By compaction of the pellets the membrane

will be damaged or distorted with a uncontrolled effect on the

dissolution rate of the tablet. The aim of the project is to in-

vestigate the combination of pellet manufacturing method,

type of polymer film and tablet excipients that minimizes the

negative effect on the dissolution rate.

(Casper Crilles Larsen, Per Holm, H.Lundbeck A/S, Jørn

Møller-Sonnergaard)

Gastrointestinal solubility of low soluble drugs (GISOL)

The GISOL-projects focus upon the in vivo and in vitro disso-

lution of low soluble drugs belonging to Class II in the

Biopharmaceutics Classification System. The research group

has established predicative dissolution methods based on

media simulating the composition of the gastrointestinal fluids

in fasted and fed states. Further, an in vitro lipolysis model

has been developed for studies of the dissolution of hy-

drophobic drug substances, e.g. danazol and probucol. The

use of the model is being investigated by studies on a range

of drug substances characterised by log P values in the


PAGE 74

range of 3 – 10; these studies are performed in collaboration

with H. Lundbeck A/S, Denmark, and Aventis Pharma, Germany.

The possibility for establishing in vivo in vitro correlations by

the use of the simulated media for dissolution testing is inves-

tigated in a study on the absorption of danazol. The effects of

meals and fluid intake are subject for a clinical study, which in

a later stage will be compared with dissolution data in order

to elucidate for example effects of the in vivo hydrodynamics.

In 2001 a new project on in vivo in vitro correlations of lipid-

based oral formulations, e.g. microemulsions and SEDDS,

has been established in the Øresund region. External partners

participating in the project are Lunds University, AstraZeneca

Lund, Cumurus, Lund, Nycomed Pharma, Denmark, DTC

Denmark and Scantox Denmark.

Other ongoing research projects concern the transport of

solubilised drug substances across Caco2 cell monolayers

and the evaluation of the micellar properties of dissolution

media simulating the jejunal fluids.

(Niels Hønberg Zangenberg, David Ilardia, Vikeke Hovgaard

Sunesen,Flemming Seir Nielsen, Anette Müllertz, Lars

Hovgaard and Henning G.Kristensen)

Lipid-based formulations for oral

delivery of low soluble drugs

Lipid-based formulations for oral delivery utilise the degrada-

tion pathways of triglycerides and other lipids to improve the

dissolution and absorption of hydrophobic drug substances.

A project on the use of tocopherols as a vehicle for low solu-

bile drugs has been concluded in 2001. The influence of

lipids upon the lymphatic transport of drug substances has

been the object for studies in the past three years, partly in

collaboration with Professor W.N. Charman, Australia. Animal

models (rats, dogs) has been established for investigating the

effects of various triglycerides on the lymphatic transport and

systemic absorption of halophantrine. In the continuation of

the project attention is paid to the pharmacokinetcs and lym-

phatically transported drug substances. Another project con-

cerns formulation and evaluation microemulsions for oral de-

livery of drugs. This project is performed in a collaboration

with H. Lundbeck A/S Denmark.

(René Holm, Janne Ørskov Christensen, Pernille Bondeskov

Nielsen, Ditte Maria Karf, Tomas Norling, Dumex-Alpharma,

Kirsten Schultz and Birgitte Mølgaard, H. Lundbeck A/S,

Betty Lomstein Pedersen, Nycomed Pharma, Anette Müllertz

and Henning G. Kristensen).

Solid lipid nanospheres

The potential use of SLN technology to reduce of the aquatic

toxicity of pesticides is investigated in a project performed in

a collaboration with Cheminova A/S. The physical stability of

SLN based on two types of lipophilic carriers is affected by

the formulation, in particular by the compatibility of the active

substance and the lipid and by the choice of surfactant. A

stable SLN system has been developed and submitted to

various tests on insects and fish.

(Henrik F. Frederiksen, Morten Pedersen, Anita Wengel and

Henning G. Kristensen)

Particulate formulation of DNA-vaccines

or protein-based vaccines

Pharmaceutical formulation of nanopheres based on lipids to

be loaded with

DNA is the subject for a collaborative research with the

State University Hospital, Copenhagen, and Statens

Seruminstitute. The research aims at a formulation intended

for mucosal application. In another project performed in a col-

laboration with Pharmexa, Denmark, the aim is to develop a

particulate vaccine formulation based on a polymeric carrier.

(Annette Vinther Heydenreich, Anne Mette Beyer, Regina

Westmeyer, Lars Hovgaard, Henning G. Kristensen, Annan

Gautam, Pharmexa, Hans Skovgaard, the State University

Hospital)

PHARMACEUTICAL FORMULATION/DRUG DELIVERY

Parenteral depot formulations

Until now, the most successful principle to control drug re-

lease from oily depot formulations have been by modifying

the partition coefficient of the drug substance, e.g. by using

prodrugs. There have been less interest in developing more

general formulation principles. In the present project, water-

in-oil emulsions are studied as potential depot formulations

for water-soluble drug substances including proteins.

(Simon Bjerregaard Jensen, Lene Jørgensen, Charlotte

Vermehren and Sven Frøkjær )

Pharmaceutical characterisation of chalcones

A number of chalcones have been shown to be effective as

antiparasitic compounds. However, this class of compounds

posseses physico-chemical properties which make the phar-

maceutical formulation challenging. Based on results from

preformulation studies, various lipid based formulations are

developed in order to optimise the therapeutic effect of se-

lected chalcones.

(Sven Frøkjær, Bente Steffansen, Agnete Dyssegaard and

Søren Brøgger Christensen, Department of Medicinal

Chemistry and Arsalan Kharazmi, Department of Clinical

Microbiology, The State University Hospital/Lica

Pharmaceutical A/S).

Protein stability

Denaturation, aggregation, and precipitation of proteins are

major problems in the formulation of protein based drugs. A


PAGE 75

Undergraduate

Researcher Agnete

Dyssegaard by the

apparatus.

more basic understanding of the molecular mechanisms for

protein fibrillation and the factors, which have an influence on

the fibrillation, may serve as a model for other globular pro-

teins and, thereby, improve the rational for developing pro-

tein-based drug in general. The kinetic of insulin fibrillation

and the effects of excipients on conformation and conforma-

tional changes on the stability of therapeutically relevant pro-

teins is studied. Other aspects of protein stability, which are

investigated, relates to the understanding of interfacial effects

on the physical stability of proteins in pharmaceutical sys-

tems.

(Liza Nielsen, Susanne Sønderkær, Susanne Møllmann,

Marco van de Weert, Sven Frøkjær, Ejvind Jensen and Peter

Langballe, Novo Nordisk A/S, Lars Lindgaard Hansen,

Pharmexa A/S, Jens Brange, Brange Consult, Ulla Elofsson,

Swedish Institut of Surface Chemistry, and John Carpenter,

University of Colorado).

Transdermal patches

The objective of project is to study the release kinetics of en-

hancers and drug substances from transdermal patches and

to study how the enhancer effect on various drug substances

is dependent on the release kinetics of the enhancer. The in-

fluence of enhancer on characteristics of importance for the

application of patches, e.g. adhesive properties, is also stud-

ied. This project is completed by December 2001.

(Michael H. Qvist, Sven Frøkjær, Flemming Madsen, Coloplast

A/S, Bo Kreilgård, Leo Pharmaceutical Products A/S and Ulla

Hoeck, Pharmacia & Upjohn)

Carrier mediated transport

Many different factors may influence on drug/prodrug absorp-

tion after oral administration. One of the main barriers for oral

drug absorption may be that many compounds display poor

permeability across biological membranes. Factors such as

the physico-chemical property of the compound, its in vitro

metabolism as well as efflux and influx transport

mechanism(s) may influence on its netto transepithelial trans-

port.

The main objective of the project is to investigate the im-

portance of carrier-mediated transport of selected com-

pounds including prodrugs, especially hPepT1-mediated

transport.

The strategies for the project are that the compounds in

question are characterized by investigating their pKa’-value(s),

aqueous stability, in vitro metabolism, affinity for hPepT1 as

well as their transepitheale transport. Structure-affinity-relation

(SAR) as well as other relations such as structure-hydrolysis

relations for various ester (model) prodrugs is an integrated

part of the project.

Pseudo-3-D image of a Caco-2 cells. Caco-2 cells grown for three weeks

in culture on permeable filters forms monolayers, which can be visualised

by confocal laser scanning microscopy. Image details: Nuclei are labelled

with propidium iodide (red) and the actin skeleton of the cells is labelled

with Alexa-488 phalloidin (green). The image was generated on a Zeiss

LSM 510 by Birger Brodin


PAGE 76


PAGE 77

A confocal laser scanning image of Caco-2 cells. The caco-2 cell line is a

commonly used cell model of the small intestinal epithelium, and express

the peptide transporter hPepT1 at the apical membrane. Image details:

Nuclei are labelled with propidium iodide (red) and the actin skeleton of

the cells is labelled with Alexa-488 phalloidin (green). The image was gen-

erated on a Zeiss LSM 510 by Birgitte Eltong/Susanne N Sørensen.

partition coefficient of the drug substance, e.g. by using pro-

drugs. There have been less interest in developing more gen-

eral formulation principles. In the present project, water-in-oil

emulsions are studied as potential depot formulations for wa-

ter soluble drug substances including peptides and proteins.

(Lene Jørgensen, Charlotte Vermehren, Sven Frøkjær and

Simon B. Jensen, Novo Nordisk A/S).

Liposomes as drug delivery system against inflammation

The project focuses on development of a specific delivery

system which carries the drug to inflammatory tissue.

Transport and release of drug may potentially be controlled by

utilizing the local conditions of the target organ, e.g. specific

enzyme activities. The phospholipid degradating enzyme,

phospholipase A2, exists in increased concentration in inflam-

matory tissue.

The degradation of long-circulating, surface modified lipo-

somes by phospholipase A2 is faster compared to conven-

tional phospholipid liposomes. Studies of the fate of surface

modified liposomes in infected tissue in rats in vivo are included

in the project as well.

The project includes studies of activity of inflammatory exu-

date containing liposome degradating factors, e.g. phospholi-

pase A2 and macrophages, toward surface modified lipo-

somes.

(Charlotte Vermehren, Sven Frokjaer, Jesper Davidsen in col-

laboration with Kent Jørgensen, Liplasome A/S and professor

Gert Storm, Department of Pharmaceutics, Utrecht Institute

for Pharmaceutical Sciences, Utrecht, The Netherlands).

Surface properties of lipid membranes

and the association of small acylated peptides

Acylated peptides and proteins can bind to surfaces of lipid

membranes by electrostatic and hydrophobic forces. Acylated

peptides and proteins display an increased circulation time in

the blood stream – which from a drug delivery perspective

make them interesting. The aim of the project is on the one

hand to investigate how the membrane association of acylated

peptides affects the lipid membrane behavior and on the other

hand how the membrane association affects the secondary

structure of the peptide.

(Tina Bjeldskov Pedersen, Sven Frøkjær, Kent Jørgensen and

Ole G. Mouritsen in collaboration with The MemPhys group,

Department of Chemistry, Danish University of Technology).

Activity of membrane associated enzymes in relation to

surface modified liposomes

Incorporation of different amounts of lipopolymers into lipo-

somes increases the in vitro and in vivo stability. This is mani-

fested as a significant prolongation of the intravascular circu-

lation time. The project involves studies of the activity of lipo-

some degrading enzymes such as phospholipase A2 and C

To improve the understanding of carrier mediated drug de-

livery certain regulatory aspects are investigated. Regulation

of hPepT-1 is a highly integrated part of the project since cer-

tain growth factors/hormones influence on expression and

transport activity of hPepT1.

Also substrate-induced regulation of hPepT1 transport

activity is investigated.

Prodrug design and SAR-analysis are primarily performed in

cooperation with Department of Medicinal Chemistry, how-

ever Leo Pharmaceuticals A/S and Zealand Pharmaceuticals

A/S are also involved to a limited degree.

(Rikke Andersen, Carsten Uhd Nielsen, Anne Engelbrecht

Thomsen, Camilla Foged, Birger Brodin, Bente Steffansen,

Andre Huss Eriksson, Thomas Andersen, and Sven Frøkjær.

In collaboration with: Mikael Begtrup, Peter Elm, Flemming

Jørgensen Department of Medicinal Chemistry; Jan Amdrup,

August Krogh Institute, University of Copenhagen; Hans

Lennernäs, University of Uppsala, Sweden; Frederik Björklin,

Leo Pharmaceuticals A/S, Denmark; Bjarne Due Larsen,

Zealand Pharmaceuticals A/S, Denmark; Mitchell E. Taub,

Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT, USA.)

Parenteral depot formulations

Until now, the most successful principle to control drug re-

lease from oily depot formulations has been by modifying the

towards surface modified liposomes. Such results are of im-

portance for a deeper understanding of the mechanisms in-

volved in the extravascular stabilization and release of incap-

sulated material from the liposomes.

(Jesper Davidsen, Charlotte Vermehren, Sven Frøkjær, in col-

laboration with Kent Jørgensen, Liplasome A/S and Ole G.

Mouritsen, The MemPhys group, Department of Chemistry,

Danish University of Technology).

NAPE-containing liposomes

Incorporation of the phospho-

lipids N-acyl-phosphatidyl-

ethanolamines (NAPE) into li-

posomes stabilizes the lipo-

somes in the presence of hu-

man serum. The stabilization

of NAPE-containing liposomes

in serum may be attributed to

different factors such as

changes in fluidity and vesicle

surface. The project focuses

on the in vivo behaviour of li-

posomes containing different

amounts of NAPE as well as

the destabilization of these li-

posomes by enzymatic degra-

dation and lipid exchange.

(Charlotte Vermehren, Sven

Frøkjær in collaboration with

Harald S. Hansen and Gitte

Petersen, Department of

Pharmacology).

Transport across

biomembranes

The objective of this project is to obtain a more basic under-

standing of key parameters of importance for passive diffu-

sion of drug substances across biological membranes. This

may contribute to the development of in vitro characterisation

programs with a greater predictive power than the methods

used to day. Presently, peptides and peptide analogs are

used as model compounds. This makes it possible to study

the importance of molecular parameters such as conforma-

tion, molecular weight, lipid-water partitioning water accessi-

ble surface, and surface polarity. The influence of absorption

enhancers on membrane transport of drug molecules is also

studied in various models.

(Lene Krarup, Jan Høst, Lars Hovgaard, Sven Frøkjær in col-

laboration with Flemming Steen Jørgensen, Department of

Medicinal Chemistry and Inge Thøger Christensen, Novo

Nordisk A/S)

Intranasal application of drugs e.g. peptides

The research is primarily concentrated on studying the poten-

tial of intranasal administration. The focus is especially on

drugs used in acute situations and delivery of peptide drugs.

The various projects include the study of in vitro/vivo perme-

ation, degradation of drugs and estimation of low irritating

potential absorption enhancers. The absorption and distribu-

tion into the brain after nasal application is also an issue.

(Erik Bechgaard, Morten Bagger, Karsten Lindhardt in collab-

oration with Sveinbjørn Gizurarson, University of Iceland)

Solubilisation of low solubility drugs

for intranasal application

The maximum volume for nasal application is normally 50-100

�l per nostril. Therefore, it is often necessary to use cosol-

vents in nasal formulations to be able to dissolve a clinical

dose. Cosolvents, however, may give rise to local mucosal ir-

ritation, why it is important to identify substances and con-

centrations, which are effective and at the same time accept-

able in relation to the indication. Various formulation aspects

are evaluated for low solubility drugs and the bioavailability

from formulations is studied in rabbits and sheep, providing

the possibility of correlating the two animal models.

(Erik Bechgaard, Karsten Lindhardt in collaboration with

Sveinbjørn Gizurarson, University of Iceland)


PAGE 78

Intranasal administration.

Intracerebral microdialysis: Probe implantation procedure per-

formed on an anaesthetised rat

Olfactory absorption

Distribution of drugs to the brain following nasal ad-

ministration

Intracerebral microdialysis in the rat has been imple-

mented as a model for studies of olfactory absorp-

tion of drugs. The model has been characterised in

terms of blood-brain barrier integrity following probe

implantation. The model has been found to be suit-

able for determinations of unbound concentrations

of drugs in vivo in the extracellular fluid of blood and

brain, based on dialysate concentrations.

Specifically, pharmacokinetic studies of drug ab-

sorption and distribution to blood and brain follow-

ing unilateral nasal administration to rats, has been

carried out using lidocaine, fluorescein and mor-

phine-6-glucuronide as model substances.

Experiments with morphine-6-glucuronide were performed as

a pilot study. With lidocaine, which easily passes the blood-

brain barrier, no signs of olfactory absorption were found, nei-

ther as higher extracellular concentrations in the brain nor as

higher absorption rates following nasal administration. With

fluorescein, which has a low blood-brain barrier permeability,

the study showed higher absorption rates and lower Tmax

values in the right side of the brain following unilateral nasal

administration indicating limited olfactory absorption in the

rat.

(Erik Bechgaard and Morten Bagger)

In vitro models for buccal mucosa

In vitro models for buccal mucosa have been employed to

study buccal permeability and toxicity of drugs, including

peptides, and pharmaceutical adjuvants.

One model is based on the cell line TR146 originating from

a human buccal carcinoma. Filter-grown TR146 cells form a

multilayered epithelium and studies of morphology, perme-

ability and profile of keratins have demonstrated a differentia-

tion pattern of TR146 cells similar to normal human buccal

epithelium. Another model is based on porcine and human

buccal mucosa mounted in the Ussing chamber. Characteris-

tics of the in vitro models have been evaluated, e.g. compari-

son of enzyme activities and the influence of molecular size

and lipophilicity on the permeability of drugs as well as the ef-

fect of bile salt enhancers. The effect of pH on the permeabili-

ty of drugs, e.g. nicotine, has been investigated.

(Jette Jacobsen, Hanne Mørck Nielsen, Margrethe Rømer

Rassing)

Toxicity assessment in the TR146 cell culture model –

development, optimization and comparison of assays

Different toxicity assays has been optimized for dividing

TR146 cells and for TR146 epithelium for three different per-

meability enhancers in order to investigate the mechanisms

of action.

(Heidi Ugelstad Eirheim, Hanne Mørck Nielsen)

Iontophoresis as a technique to enhance

in vitro buccal drug delivery

Iontophoresis as non-invasive physical enhancer in buccal

drug delivery has been studied. The results demonstrated the

feasibility of the iontophoretic approach to enhance and con-

trol the rate of buccal drug delivery. A new three-chamber

iontophoretic diffusion cell has been developed to reflect the

in vivo iontophoretic drug delivery more closely.

(Jette Jacobsen, Margrethe Rømer Rassing)

Epidermal growth factor (EGF): in vitro and in vivo

studies and clinical testing of treatment of oral

mucositis induced by radiotherapy

The overall objective of the project is the introduction of a

new medical therapy with topical application of EGF in cancer

patients to relief oral mucositis induced by radiotherapy. The

project includes studies on EGF on the cell line TR146, devel-

opment of a pharmaceutical formulation with EGF, studies of

the healing effect of EGF on oral mucositis and clinical testing

of the pharmaceutical formulation. Initial studies have been

carried out.

(Hanne Mørck Nielsen, Margrethe Rømer Rassing in collabora-

tion with Helle Birgitte Dahl Olin, Maria Elisabeth Christensen,

State University Hospital)


PAGE 79

Intercellular matrix in the TR146 cell culture model and in

vivo/in vitro correlation to human buccal epithelium.

The objective of the project is to characterize the lipid content

of the intercellular matrix in the TR146 cell culture model and

to examine the influence of different enhancers on the lipid

structure. Furthermore, to correlate the permeability of drug

substances across the TR146 cell culture model to the per-

meability across human buccal mucosa in situ. For the in vivo

studies a custom-designed chamber has been developed.

Nicotine has been chosen as a first model substance.

(Charlotte Adrian, Margrethe Rømer Rassing in collaboration

with Helle Birgitte Dahl Olin, State University Hospital)

CLINICAL PHARMACY

Development and maintenance of a quality assurance system

for the medication procedures in a critical care unit.

The aim of the project is to reduce the number of medica-

tion errors and to improve drug therapy.

(Lona Christrup, Mette Rasmussen in collaboration with

Intensive Care Unit, Herlev University Hospital ).

Long-term treatment of chronic pain patients with morphine

The aim of the study is to gain knowledge of the connection

between dose/administration route, plasma concentration of

morphine/morphine metabolites and side-effects and analge-

sia, in order to improve the treatment of patients suffering

from chronic pain.

(Lona Christrup, Steen Honoré Hansen, Department of

Analytical and Pharmaceutical Chemistry, in collaboration with

the Multidisciplinary Pain Centre, Herlev University Hospital).

Local ocular pain treatment with opioids

The aim of the project is to evaluate if opioids applied locally

in the eye can exert analgesia if it is mediated by peripheral

opioid receptors. The transport of opioids across the cornea

and the distribution in the eye are investigated in vitro and in

vivo in rabbits. Additionally, the analgesia following adminis-

tration of opioids in the eye in a clinical set up is investigated.

(Lona Christrup, Bente Steffansen in collaboration with

Department of Pharmacology, The Royal Veterinary and

Agricultural University, The Pain Clinic, Aalborg University

Hospital, and the Multidisciplinary Pain Centre, Herlev

University Hospital).

LAAM - potential use as an opioid analgesic

LAAM is an opioid drug, and when used in the maintenance

treatment of drug addicts to suppress abstinence syndroms,

it has a duration of action of 3-4 days. The purpose of the

study is to evaluate if LAAM has a future as an analgesic drug

substance. The binding of LAAM and its two metabolites nor-

and dinor-LAAM to the opioid and NMDA receptors is investi-

gated in vitro. The analgesic effect of all three substances is

evaluted after administration in mice. The duration of action

with respect to analgesia as well as the equipotential doses

to methadone is investigated in patients suffering from chron-

ic pain. Finally, a HPLC method for quantification of LAAM

and its metabolites is being set up.

(Lona Christrup, in collaboration with H:S Multidisciplinary

Pain Centre, Copenhagen University Hospital and Department

of Clinical Biochemistry, Bispebjerg University Hospital).

Pharmacokinetics and -dynamics of paracetamol

The pharmacokinetic and -dynamic parameters of paraceta-

mol are investigated in adult postoperative patients in order to

optimize pain management with paracetamol.

The pharmacokinetics of paracetamol are also investigated

in the postoperative phase in children.

Oral, intravenous and rectal administration is used.

(Mette Rasmussen and Janne Rømsing in collaboration with

physicians at hospitals in Copenhagen, and Tina Hahn,

Coloplast A/S)

Non-opioid analgesics

To improve postoperative pain management in ambulatory

surgery patients, several projects are carried out evaluating

the analgesic effect of non-opioid analgesics. The research

focuses on mechanism of action, pharmacokinetics and -dy-

namics, and side effects of the drugs. The use of a multi-

modal approach as well as the influence of different formula-

tions of the drugs on analgesia are investigated.

(Janne Rømsing, Tina Hoff Duedahl in collaboration with

physicians at Herlev and Gentofte University Hospitals and at

the State University Hospital).

Pharmacokinetics of prednisolone.

The prognosis for children with acute lymphoblastic leukemia

depends on the amount of residual disease after four weeks

of treatment. In this project, a possible correlation between

the plasma concentration of prednisolone and the amount of

residual disease is evaluated. Further, the kinetics of pred-

nisone is examined and the bioavailability is evaluated in rela-

tion to the gastro-intestinal function. Oral and intravenous ad-

ministration is used.

(Kamilla B. Petersen and Mette Rasmussen in collaboration

with physicians at The National University Hospital,

Rigshospitalet).


PAGE 80


PAGE 81

Department ofPharmacology

The Department of Pharmacology conducts research and

teaching within a broad biological field including biochemistry,

microbiology, physiology, pharmacology, pharmacotherapy

and molecular biology focusing on effects and side effects of

drugs and their importance in connection with pathological

conditions.

A detailed broad spectrum of knowledge about drug effects

and the methods used to investigate them at cellular levels, in

isolated tissues, in the whole animal and in patients, is of fun-

damental importance and an indispensable basis for drug ex-

perts. The teaching gives pharmacists in-depth knowledge

about biochemistry and microbiology, including molecular bi-

ology and integrated pharmacological knowledge in which

anatomy, physiology, pharmacology and biological standard-

ization are integrated. This knowledge will enable pharmacists


Head of Department: Associate Professor Erik Wind Hansen, PhD

PAGE 82

to function as drug experts. The research at the Department

forms the scientific basis for the education.

RESEARCH

Research at the Department of Pharmacology covers a wide

range of activities directed at drugs, their effects and side ef-

fects, their importance in connection with pathological condi-

tions, as well as their effects on the immunological system.

Research includes biochemical, pharmacological, pharma-

cokinetic and molecular biological studies related to charac-

terisation and development of specific drugs. It is based on

studies in cell cultures, isolated tissues and smaller animals

and includes, among other thing, characterisation of recep-

tors, transport systems in cell membranes, mechanisms for

regulation of biosynthesis and for release of peptides, studies

of second messengers, intracellular mechanisms and various

gene techniques. Primary research fields are pharmacology

(including neuro-, molecular- and vascular pharmacology),

molecular biology and pharmaceutical microbiology.

Pharmacological research aims to improve the clinical use

of drugs. Current research in the vascular pharmacological

area focuses on the transduction mechanisms for peptides

and classical neurotransmitters in cerebral, ocular and coronal

vascular tissues from animal and humans in relation to dis-

eases like migraine, ischæmia and diabetes. Neuropathic pain

is a new research field at the Department. A set of rat models

for neuropathic pain is under establishment for testing with

new and well-known antagonists and agonists for the in-

volved receptor systems. The goal of the project is to improve

the treatment of neuropathic pain.

The molecular- and neuropharmacological research seeks

to improve understanding of the effects of neuro-active amino

acids, an important part of the efforts to develop new drugs

to treat neurodegenerative diseases. The research is interdis-

ciplinary in its combination of molecular, cellular and pharma-

cological aspects of neurotransmitters. Current research fo-

cuses on GABA as a neurotransmitter, on glutamate- and

GABA-mediated neurotransmission, on the formation of en-

docannabinoids and on opioid- and NMDA-receptors using

cell cultures, isolated tissues and electrophysiological tech-

niques. The molecular and cellular role of different mediators

e.g. cytokines and nitrogen oxide in neurotoxic and neuropro-

tective effects in the brain is another issue in neuropharmaco-

logical research. Communication between the neuroendocrine

and the immune system in the neurohypophysis is another

area of study. Other research objects are the biological func-

tion of essential fatty acids and phospholipases in the cell

membrane, receptor mediated regulation of intercellular en-

zymes and the formation of second messengers.

The molecular biology group uses genetic engineering to

generate novel antibodies and peptides relevant to the diag-

nosis and treatment of immunological diseases. Current re-

search focuses on generating recombinant antibodies with

antigen-specific MHC restricted specificity of T cells used as

reagents for basic and clinical investigations and immunother-

apy. The detailed involvement of selected viral surface pro-

teins in viral infection cycle is another area of investigation.

Pharmaceutical microbiological research focuses on the de-

velopment of new methods to evaluate pharmaceuticals.

Current research concerns in vitro pyrogen testing based on

the use of cell lines.

TEACHING

The Department teaches compulsory theoretical courses in

biochemistry, physiology and biological standardisation, mi-

crobiology, anatomy, pharmacology and pharmacotherapy to-

gether with laboratory courses in microbiology and pharma-

cology. In the period under review, the Department taught

elective courses in pharmacokinetics and pharmacodyna-

mics, basic methods in molecular biology, experimental phar-

macology in-vitro, biochemical laboratory technique, micro-

biological and immunological methods of drug control.

The work to make a radical change in teaching in order to

focus on pharmacology continues. The new curriculum will

come into force starting next term, which means that courses

in anatomy, physiology and biological standardisation and

pharmacology will be integrated into two courses: basic phar-

macology and organ-related pharmacology. The Department

of Pharmacology together with the Department of Pharmacy

DEPARTMENT OF PHARMACOLOGY

PAGE 83

also held a compulsory course in pharmacotherapy. Finally,

an introductory course in cell biology was introduced.

About 40 students have completed their master’s theses in

connection with the Department; half of these students re-

ceived their practical training in foreign research laboratories

(pharmaceutical industry and abroad).

Some staff members were involved in PhD courses both at

the School and at other universities again this year.


Klaus Bahl Andersen is censor of Aarhus University,

December 2001.

Ole J. Bjerrum is Adjunct Professor of Centre for Proteome

Analysis, University of Southern Denmark. Fellow, Danish

Academy of Natural Sciences. Fellow, Danish Academy of

Technical Sciences. Danish delegate: EU 5th Framework

Programme Management Committee on Quality of Life.

Member of Governing board, European Association for pro-

motion of Science & Technology (EUROSCIENCE). Member of

Faculty, European Centre for Pharmaceutical Medicine

(ECPM). Appointed member, Advisory Research Council,

Ministry of Health. Appointed member, Advisory group for EU

5th Framework programme for Quality of Life and Mobility

and Training, IT and Research Ministry. Appointed member,

Advisory board Danish Technology Council. Member of

Scientific Committee for EUFEPS Conference on Optimizing

Drug Development: “Use of Biomarkers: From Drug Discovery

through Clinical Practice”, Basel, December 2001. Chairman

for EUFEPS Conference on Optimizing Biotech Medicine:

“Rational Development of Therapeutic Proteins”, Berlin, May

2002. Member of Organizing Committee Eufeps Congress:

“EUFEPS 2002. New Safe Medicine Faster”, Stockholm,

October 2002. Organizer of Course of Industrial Drug Deve-

lopment for Danish Pharma industry and Danish School of

Pharmacy.

Jan Engberg is member of the reviewing boards of: Immuno-

technology, Biochim. Biophys. Acta, Journal of Immunological

Methods, Nucl. Acids Res, Trends of Biochemical Sciences,

Biotechnology, FEBS-letters and Proceedings of the National

Academy of Science (USA). He is member of the advisory

boards of the National Research Councils for medical scien-

ces in Holland, Sweden and Australia and member of evalua-

tion committees at the faculties of Medical and Natural Scien-

ces in Copenhagen, Aarhus, Odense and Roskilde.

Bjarne Fjalland is member of the reviewing board of: Eur. J.

Pharmacol., Eur. J. Physiol., J. Neuros. Res., Psychopharma-

cology and Pharmacology & Toxicology.

Aase Frandsen is President of the Danish Society for

Neuroscience and member of the council for The National

Association for Treatment of Brain Disease. She is member of

the council for The Federation of European Neuroscience

Societies (FENS) and member of the governing council for

International Brain Research Organisation (IBRO). Organizer

of meeting of EU consortium ERDYS. Editor of Journal of

Neurochemistry. Referee for Journal of Neurochemistry,

Neurochemistry International, Brain Research, Neuropharma-

cology, Journal of Cerebral Blood Flow and Metabolism,

European Journal of Biochemistry, Journal of Clinical Ana-

tomy, and Journal of Neuroscience Research. Officially ap-

pointed examiner at the University of Copenhagen.

Georgi Gegelashvili is member of the reviewing boards of

Neuroreport, J. Neurotrauma, Brain Research, FEBS Letters,

and J. Neurosci. He serves as a vice-chairman for the

Georgian NeuroForum and represents this society in the

European Glia Network.

Harald S. Hansen censor at DTU and KVL and has been in-

ternational reviewer for a grant application to Science Foun-

dation Ireland. He has been member of the assessment com-

mittees for PhD-theses at DFH, at Biocentrum-DTU and at

Syddansk University Odense and been chairman for the as-

sessment committee for a professorship at DFH. He is mem-

ber of the Board of directors for The Danish Nutrition Society,

for International Society for the Study of Fatty Acids and

Lipids (ISSFAL), is alternate member of The Danish Commit-

tees on Scientific Dishonesty, the Danish State Nutrition

Council, is member of 2 consulting groups affilated to the

Danish State Nutrition Council concerned with “Dietary fat,

children and atherosclerosis” and “Dietary prevention of obe-

sity”, and chairman for the National Council of Nutritional

Science at the Royal Danish Academy of Sciences and

Letters.

Inger Jansen Olesen is member of the Danish Pharmaco-

logical and Toxicological Society, the International Headache

Society, The International Society of Cerebral Blood Flow and

Metabolism. She is a member of the reviewing board of Br. J.

Pharmacol., Stroke and Cephalalgia.

Arne Schousboe is member of Editorial Board of: J. Neuro-

chem., Neurochem. Res., Neurochem. Int. (Assoc. Ed.), J.

Neurosci. Res. (Assoc. Ed.), Exp. Brain Res., Glia, Int. J. Devl.

Neurosci. (Assoc. Ed.), Devl. Neurosci. and Eur. J. Pharmacol.

He is external examiner at the Faculty of Health Sciences and

the Faculty of Science, University of Copenhagen. He is a

member of the Advisory Board of the National Science

Foundation (USA), Medical Research Council (UK), The

Wellcome Trust (UK) and Human Frontier Science Program


PAGE 84

(France). He is registered in the ISI-Thomson list “Highly Cited

Researchers” of the 100 most frequently cited researchers in

the field Neuroscience (www.isihighlycited.com).


Tue Banke has received a post-doc scholarship from The

Alfred Benzon Foundation for a stay of one year at Dept.

Pharmacol., Emery Univ., Atlanta, Ge, USA and has received

a 3-year post-doc scholarship from The Danish Medical

Research Council (2002-2004).

Ole Jannik Bjerrum has received DKK 15.000 from Novo

Nordic, DKK 350.000 from EU Accompanying Measures:

EUFEPS 2002: New Safe Medicine Faster. An integrated

Congress.

Jan Engberg has received The following funding (for projects)

DKK 150.000 from The Danish Cancer Society “Generation

of recombinant antibodytoxins directed against tumor associ-

ated peptide/HLA complexes with T cell receptor-like speci-

ficity”, DKK 312.715 from The Novo Nordic Foundation

“Generation of recombinant antibodies specific for MHC/pep-

tide complexes of relevance for the pathogenesis of multiple

sclerosis”, DKK 89.660 from The Danish Research Council

for Medical Sciences. Identification of hippocampus specific

corticosteroid-specific genes using DNA micro arrays and

DKK 300.000 from Apotekerfoundation “Generation of re-

combinant antibodies specific for MHC/peptide complexes of

relevance for the pathogenesis of multiple sclerosis”.

Bjarne Fjalland has received DKK 200.000 from The Lund-

beck Foundation and DKK 100.000 from Ib Henriksen

Foundation in support of the project “CGRP - an important

partner in painperception”.

Aase Frandsen has received DKK 60.000 from SSVF Start

Program (22-01-0054).

Georgi Gegelashvili continued to administer research grants

received DKK 600.000 per year, for the period 1998-2002

from The Danish Medical Research Council, DKK 40.000

from The Novo Nordic Foundation. He has obtained further

funding DKK 88.350 from The Novo Nordisk Foundation for

the period 2001-2002, and DKK 260.000 from The Danish

Medical Research Council for year 2002. He has received a

senior visiting fellowship and a research grant from The Alfred

Benzon Foundation DKK 150.000 for a project carried out in

the USA 2000-2001. He has been awarded a Bøje Benzon

Stipendium DKK 520.000 per year.

Harald S. Hansen has received DKK 750.000 from SSVF,

DKK 280.000 from Carlsberg Foundation, DKK 400.000

from Lundbeck Foundation, DKK 300.000 from Augustinus

Foundation, DKK 50.000 from Director Ib Henriksens

Foundation, DKK 100.000 from Eva & Henry Krænkels

Memorial Foundation, DKK 90.000 from Novo Nordic

Foundation.

Arne Schousboe had a 3-year grant from The Lundbeck

Foundation (DKK 400.000 per year (1999-2001)). He has re-

ceived a 3-year grant from The Danish Medical Research

Council (2001-2004; DKK 500.000 per year).

Helle S. Waagepetersen has a 31/2-year (2000-2003) post-

doc grant (DKK 600.000 per year) from The Danish Medical

Research Council.

STAFF

In the past year Ole Jannik Bjerrum was appointed professor

of pharmacology and the position of associate professor in

pharmacology was reappointed. At the moment two positions

as associate professors in pharmacology are vacant due to

resignation. One position has been upgraded to a full profes-

sorship in pharmacokinetics and drug metabolism. It is hoped

that the position will be filled soon. The Department is staffed

by five professors (one vacancy), 16 associate professors

(one vacancy), one assistant professor, three external associ-

ate professors, three senior clerks, 13 laboratory technicians,


PAGE 85

In the year passed Ole Jannik Bjerrum has been

appointed as professor in pharmacology

one temporary laboratory technician, one trainee, three labo-

ratory porters, one assistant and four cleaners. At present 17

PhD students are employed at the Department. In addition

several research assistants and technicians are employed on

grants from external funds. Several staff members (both sci-

entific and technical-administrative staff) have left their posi-

tions for jobs primarily in the pharmaceutical industry.

PROJECTS

NEUROPHARMACOLOGY

GABA as transmitter

The project deals with secretion from the intermediate- and

posterior hypophysis. The existence of numerous neuropep-

tides and neurotransmitters as well as receptors for different

neuroactive substances has been shown in the hypophysis.

In different in vitro systems the pharmacological significance

of neuroactive substances for secretion of hormones is inves-

tigated. In the year passed the GABA-receptors in the hy-

pophysis have been in focus. The influence of different neu-

rosteroids on the GABA-receptors in the hypophysis has

been investigated by means of electrophysiological tech-

niques in slices from rat hypophysis (patch clamp) and on iso-

lated organs. It has been shown, that there are several bind-

ing sites for neurosteroids at the GABA-receptors and that

there are difference in the sensitivity of the receptors in the

intermediate- and posterior hypophysis.

The connection between the pharmacology of GABAA-

receptors and there subunit composition is examined by a

combination of patch-clamp electrophysiology and RT-PCR

analysis of mRNA at single nerve cells. By use of cell cultures

and slices from different part of the brain the regional variation

of the characteristics of the GABA-receptors is examined (co-

operation with F.F. Johansen, Neuropathological laboratory,

University of Copenhagen).

The pharmacology and mechanism of receptoractivation for

partial GABAA-agonists are examined by patch-clamp electro-

physiology in cultures of nerve cells. The effect of substances

with modulating effect at GABAA-receptors (benzodiazepines,

barbiturates, neurosteroids and metalions) is also examined

as well as new substances synthesised at the Department of

Medicinal Chemistry (Cooperation with J.D.C. Lambert, De-

partment of Physiology, University of Århus and researchers

at Department of Medicinal Chemistry, Royal Danish School

of Pharmacy).

(Uffe Kristiansen, Bjarne Fjalland, Bjarke Ebert, Suzanne

Hansen, Henrik Vestergaard, Gunilla Steven)

Communication between the immune

and the neuroendocrine system

The research is dealing with the communication between the

immune and the neuroendocrine system at the neurohy-

pophysial level. In previous experiments we have shown the

ability of interleukin-1� to stimulate the release, both in-vivo

and in-vitro, of oxytocin and vasopressin. At the present we

are investigating the pattern of cytokines release from cul-

tured glia cells from the neurohypophysis (pituicytes) and the

mechanisms which control this release. The main objective is

to elucidate whether a paracrine communication between the

pituicytes and the axonal terminals in the neurohypophysis

exists.

(Jens Juul Dencker Christensen, Erik Wind Hansen, Lise

Moesby, Tine Klavsen, Janne Møgelhøj Colding, Helle

Dyhrfjeld, Betina Schøler)

MOLECULAR PHARMACOLOGY

In collaboration with the neuromedicinalchemical group at the

Department of Medicinal Chemistry the pharmacological

characterisation of new substances at glutamate- and GABA-

receptors is undertaken. The binding profile of new radio-

active glutamate and GABA-ligands is investigated by means

of binding studies in homogenates and receptorautoradio-

grafic methods.

In collaboration with the neuromedicinalchemical group and

the research institute at Merck, Sharp & Domes in England

the connection between the subunit composition of humane

GABA-receptors and the pharmacological profile of a series

of agonists, partial agonists and antagonists is examined.

With the purpose of development of new strategies to treat

neuropathic pain a series of strong analgesics is investigated

in receptorbinding models, isolated organs and electrophysio-

logically with respect to effect on the NMDA-receptors.

(Bjarke Ebert, Martin Mortensen, Bjarne Fjalland, Durita

Poulsen)


PAGE 86

Pathophysiological investigation of neuropathic pain

through pharmacological intervention

Pain of nerve injury (neuropathic pain) is difficult to treat.

Preclinical and clinical experiments with analgetica have

shown discrepancy which probably reflecting individual pa-

tient variation in the activation of the pain provoking mecha-

nisms of sensing, transmission and transduction. The goal of

the project is through better knowledge of the patophysiologi-

cal mechanisms to improve the individual treatment regimen.

A set of rat models for neuropathic pain is under establish-

ment for testing with new and well-known antagonists and

agonists for the involved receptor systems.

(Ole J. Bjerrum and Majid Sheykhzade)

Neurotoxic and neuroprotective effects of nitrogen oxide

Nitrogen oxide (NO) is involved in both neurotoxicity and neu-

roprotection depending on where, when, why, how and how

much NO is formed. Thus, NO formed from eNOS under is-

chemia is neruroprotective whereas NO from nNOS and iNOS

under this condition is neurotoxic.

Using primary cultures of cortical neurons and cerebellar

neurons we are studying the formation of NO under different

neurotoxic stress stimuli and trying to correlate the amount or

character of NO formed with cell death or survival. To further

elucidate the mechanism of action we are studying the intra-

cellular targets for NO with special emphasis on mitochondria

as we have found that NO inhibits respiration in neurons.

(Trine Meldgaard Lund, Gunilla Steven, Marianne Michaëly,

Arne Schousboe in collaboration with John Garthwaite, UCL,

UK)

Glutaric aciduria type 1 – a metabolic disease

with neurodegenerative symptoms

Patients with glutaric aciduria type 1 have mutations in the

gene coding for the glutaryl-CoA-dehydogenase enzyme. This

enzyme is essential in the catabolism of lysine, hydroxylysine

and tryptophan, thus an accumulation of the metabolites 3-

hydroxy-glutaric acid, glutaric acid and glutaconic acid is

seen in these patients. The objective of this study is to eluci-

date whether these metabolites are responsible for the neu-

ropatological findings in these patients. Using cultures of cor-

tical neurones we are studying the viability of the cells after

treatment with the metabolites and have found that they are

neurotoxic. We are now in the process of finding the target

for these neurotoxic compounds, this probably being the

NMDA subtype of glutamate receptors, having ruled out any

effect on the other glutamate receptor subtypes and gluta-

mate uptake.

(Trine Meldgaard Lund, Arne Schousboe, Darryl Pickering,

Anders S. Kristensen in collaboration with Allan Meldgaard

Lund and Ernst Christensen, Department of Clinical Genetics,

Copenhagen University Hospital)

Characterization of glutamate receptors

In order to investigate the role of the various AMPA receptors

(AMPA-R) in the normal functioning of the brain (e.g. memory

formation), as well as their role in pathological conditions (e.g.

stroke, epilepsy, Alzheimer’s disease), it would be highly ad-

vantageous to have subtype-selective agonists and antago-

nists. The latter could have potential applications as thera-

peutics.

Using the cloned, recombinant wild-type and mutant rat

AMPA-R (GluR1-4) we have made significant progress in the

last year towards an understanding, at the molecular level, of

the properties of both the receptor proteins and of the ago-

nist chemical structures that can lead to subtype selectivity

and increased affinity and potency. Site-directed mutagenesis

of GluR1 and GluR3 have revealed amino acid residues within

the vicinity of the agonist binding site that are responsible for

controlling both agonist affinity and desensitisation kinetics.

Using this experimentally gained information, we have em-

ployed computer homology modelling of GluR1-4 to predict

new structures of compounds that should have increased po-

tency, affinity and selectivity. In the future, we hope to be able

to increase our current selectivity factor of 125-fold to > 1,000-

fold.

(Darryl Pickering, Anders S. Kristensen, Tue G. Banke and

Arne Schousboe in collaboration with Ulf Madsen, Jeremy

Greenwood and Tommy Liljefors, Dept. Med. Chem.)

Characterization of GABAA receptors

Using Sf9 cells as an expression system the assembly pro-

cess for GABAA receptors has been investigated. In receptors

formed from �1, �2 and �2 subunits it was found that musci-

mol (GABA agonist) binding appears prior to binding of fluni-

trazepam (modulator) or TBPS (channel blocker). Thus, bind-

ing of the agonist may not require a fully formed operational

receptor complex of a pentameric configuration. It was addi-

tionally shown that the �2 subunit plays a key role in the re-

ceptor assembly process. The chimeric subunits �1/�2 and

�2/�1 representing the extracellular N-terminal domain of �1

and �2 subunits, respectively have been used in combination

with �2 and �2�2 to elucidate the significance of these do-

mains for desensitization. The �1/�2 chimara did not exhibit

desensitization after GABA stimulation independent of the

combination with �2 or �2�2. This suggests that the C-termi-

nal segment of the �1 subunit may be important for the de-

sensitization properties. More detailed investigations of site

directed mutagenic receptors may allow identification of the

molecular site involved in the desensitization mechanism.

(Lisbeth Elster, Claus F. Poulsen, Darryl Pickering, Uffe

Kristiansen and Arne Schousboe in collaboration with Dr.

R.W. Olsen, Dept. Mol. Med. Pharmacol., UCLA, Los

Angeles, CA, USA)


PAGE 87

Characterization of GABA transporters

GABA transporters cloned from mouse (GAT1-4) and tran-

siently expressed in HEK cells have been used to study the

subtype selectivity with regard to inhibition of GABA transport

by a number of lipophilic derivatives of exo-THPO. All ana-

logues inhibit GABA transport mediated by GAT1 and a small

number of these also exhibited inhibitory activity for GAT2.

The anticonvulsant activities of exo-THPO has been com-

pared with that of its N-methyl and N-ethyl derivatives previ-

ously identified as inhibitors of neuronal and astrocytic GABA

uptake with differential potency. It was found that the potency

as antivonvulsants in mice prone for audiogenic seizures cor-

relates with the potency of these compounds as inhibitors of

astroglial GABA uptake but not to that as inhibitors of neu-

ronal GABA uptake. The GABA transporters specificity of a

new series of GABA-analogues, amino-cyclohexane car-

boxylic acid derivatives with lipophilic side chains, are now

under investigation. These compounds exhibit a novel phar-

macological profile with regard to inhibition of subtypes of

GABA transporters.

(Orla M. Larsson, Alan Sarup, Darryl Pickering, Lone

Petersen, Helle Dyhrfjeld and Arne Schousboe in collabora-

tion with Bente Frølund, Rasmus P. Clausen and Povl

Krogsgaard-Larsen, Dept. Med. Chem. and Dr. H.S. White,

Dept. Pharmacol., Univ. Salt Lake City, SLC, Utah, USA)

Glutamate metabolism and transport

in neurons and astrocytes

Using cerebellar astrocytes and granule neurones in mono-

and cocultures, 13C- and 15N-labeled glutamine, lactate and

alanine and NMR and GC-MS technology, it has been shown

that transfer of ammonia nitrogen between glutamatergic neu-

rons and astrocytes to some extent can be accounted for by

a lactate-alanine shuttle transporting alanine from neurones to

astrocytes and lactate in the opposite direction. Glutamate re-

leased from neurones is transported into astrocytes via two

different transporters GLAST and GLT-1. The regulation of the

expression of these transporters has been investigated using

specific antibodies and it has been shown that activation of

neurotrophine receptors on the astrocytes plays an important

role in this process. Moreover, it appears that intracellular sig-

naling pathways such as the MAP kinase pathway are in-

volved. Additionally, we have investigated the possibility of us-

ing a newly developed non-transportable glutamate trans-

porter inhibitor threobenzyloxyaspartate (TBOA) as a tool to

distinguish between vesicular and carrier mediated depolar-

ization coupled neuronal glutamate release. It was demon-

strated that TBOA blocks the carrier mediated release without

affecting the vesicular release during K+-induced depolarization

of glutamatergic cerebellar granule neurones in cell culture.

(Helle S. Waagepetersen, Georgi Gegelashvili, Alan Sarup,

Kirsten Thuesen and Arne Schousboe in collaboration with

Dr. U. Sonnewald, Univ. of Trondheim, Norway, Dr. N.C.

Danbolt, Univ. of Oslo, Norway and Dr. Jens Zimmer, Univ.

Odense)

Heterogeneity of astrocytic mitochondrial metabolism

Using 13C-labeled lactate or glucose and subsequent NMR

and GC/MS analysis of samples from astrocytes and their in-

cubation media it has been demonstrated that these two

substrates are differentially metabolized by these cells.

Moreover, it was shown that astrocytic mitochondria are het-

erogeneous since different populations are involved in biosyn-

thesis of releasable citrate and glutamine. A model of four dif-

ferent types of mitochondria with TCA cyclus associated with

metabolism of acetyl CoA derived from exogenously supplied

or endogenuously produced lactate has been proposed.

Further experimentation is needed to shed light on the func-

tional importance of such heterogeneity.

(Helle S. Waagepetersen, Orla M. Larsson, Kirsten Thuesen

and Arne Schousboe in collaboration with Dr. U. Sonnewald,

Univ. of Trondheim, Norway.).

(Tue Banke, Hanne Danø, Lisbeth Elster, Georgi Gegelashvili,

Anders Skov Kristensen, Orla M. Larsson, Lone Petersen,

Darryl Pickering, Claus F. Poulsen, Alan Sarup, Arne

Schousboe, Kirsten Thuesen and Helle S. Waagepetersen)

The cytoprotective role of ER-stress proteins.

The Endoplasmatic reticulum (ER) plays a central role in the

cellular stress response as the structure where protein modifi-

cation, processing and quality control are exerted. In addition,

the ER is the intracellular reservoir for Ca2+, an ion involved in

many signalling reactions, including those mediating the

stress reponse. A protein in the lumen of the ER called

GRP78 (Glucose Regulated Protein or BiP (immunoglobulin

Heavy Chain Binding Protein) is homologous to the cytosolic

chaperone and stress protein HSP70. GRP78 is a member of

a family of stress proteins (including e.g. GRP94, GRP75,

GRP58, GRP170) that all functions as stress proteins. While

the cytoprotective role of the GRP-family, especially GRP78,

is well documented within the fileds of cancer biology and im-

munology very little evidence has been obtained from neuro-

biological research. GRP78 obtains a key positions as a

chaperone protein in connection with the synthesis of ER-

associated ribosomes and protein tanslocation into the lumen

of ER. GRP78 is upregulated significantly on the levels of

mRNA and protein in in vitro as well as in vivo models of

ichemia. This emphasizes the possible cytoprotective role of

GRP78 in ischemia and other conditions involving glutamate

toxicity.

Recently we have observed that a 16 hours pre-treatment

with low, non toxic doses of the EAA NMDA significantly re-

duces the cytotoxic potential of subsequent exposure to toxic

doses of NMDA (the phenomenon of tolerance). This phe-


PAGE 88

nomen is accompanied by a significant (up to 80%) upregula-

tion of GRP78. We are currently working on characterization

of the pharmacological basis for the establishement of the tol-

erance. Furthermore, it is investigated whether or not there is

a causal relation between GRP78 and the NMDA mediated

tolerance against glutamate toxicity. Likewise the influence of

GRP78 on EAA mediated Ca2+ signals is investigated.

(Aase Frandsen, Pia Birch Nielsen, Paulo Girao, Arne

Schousboe).

(GRP expression in collaboration with Professor Wulf Pachen,

Dept of Exp neurology, Max-Planck Institute of Experimental

Neurology, Cologne)

The role of cytokines in neurodegeneration

and neuroprotection

New results indicate a common area of function between the

stress activated signalling from the ER and signalling through

TNF p55- receptors (TNFR1). This area arises through an ac-

tivation of the transcription factor NF-�B through an internal

stress stimulus to the ER (EOR, ER overload response). An

externally released NF-�B activation is seen e.g. when TNF

binds to TNFR1. This binding recruits the transduction mole-

cules FADD/MORT1 (FAS associated death domain protein)

and RIP (receptor interacting protein). FADD/MORT1 medi-

ates the proapoptotic effect of TNF whereas the RIP activates

the antiapoptotic effect of NF-�B. In primary cultures from

TNFR1-deficient mice we are currently investigating if changes

in NF-�B (and other pro- and antiapoptotic factors) specifical-

ly can be ascribed to the lack of the TNFR1-receptor or

changes in the EOR.

(Aase Frandsen in collaboration with Prof. Bente Finsen and

coworkers, University of Odense)

The role of IFN� in toxicity induced in CNS

induced by ischemia or inflammation

The sensitivity of nerve cells towards ischemic damage is in-

creased by IFN�. Even though IFN� not normally are found in

association with ischemia in the brain, this finding allows the

possibility that IFN� alone or in combination with e.g. EAAs

and TNF in a fundamental manner may change the suscepti-

bility of the CNS not only to ischemic conditions but also in

connection with leucocyte infiltration in the brain seen in pa-

tients with disseminated sclerosis. Recently, we have demon-

strated that IFN� is potentiating the toxic effect of NMDA and

AMPA in cultured neurons from IFN� deficient mice, and we

are currently investigating the pharmacology of this response.

(Aase Frandsen in collaboration with Prof Bente Finsen and

coworkers, University of Odense)

CUSTOM MADE ANTIBODIES

Generation of recombinant antibodies recognizing

MHC/peptide complexes of relevance for

the pathogenesis of multiple sclerosis

The purpose of the project is to generate antibodies recogniz-

ing specific MHC/peptide complexes of relevance for the

pathogenesis of multiple sclerosis. The strategy is that such

reagents will be useful in modulating the autoaggresive T cell

response. To generate such antibodies we use the so-called

page display technology where the total antibody repertoire of

immunized animals are cloned and expressed in bacterial

cells. The antibody libraries are generated by a PCR (Poly-

merase Chain Reaction) based method and allows for isola-

tion of the wanted specificity through positive selection.

Generation of antibodies that recognize specific

MHC/peptide complexes of relevance for

the pathogenesis of specific melanoma cancers

Studies of melanoma patients have revealed the identity of

activated T cells specific for defined MHC/peptide complexes.

These peptides are derived from tumour associated antigens.

Thus, these MHC/peptide complexes become cell surface

markers for these malignancies. We want to use the techno-

logy described above to generate antibodies specific for

these MHC/peptide complexes since we have shown previ-

ously that such antibodies can be conjugated with cytotoxic

reagents with the effect of killing cells in a MHC/peptide-

specific manner.


PAGE 89

of the three NOS enzymes that is upregulated and their local-

ization. Furthermore, it will give us an increased understand-

ing of the mechanisms underlying an eventual hyper- or hy-

poreactivity of cerebral blood vessels after mental stress.

(Inger Jansen Olesen, Tina Zinck, Majid Sheykhzade, Trine

Meldgaard Lund, Kirsten Busk)

Studies of the effect of glyceryltrinitrate infusion in rat on

nitric oxid synthase in dura and cerebral blood vessels

NO is a powerful vasodilator of general importance for the ar-

terial diameter. It was recently shown that NO is of main im-

portance in the migraine pathogenesis. A 20 minute intra-

venous infusion of glyceryltrinitrate (GTN) induce a migraine

attack fulfilling the criteria for migraine without aura, in mi-

graine patients at an average time of 5.5 hrs after the infu-

sion. Furthermore, L-NMMA, an inhibitor of NOS is effective in

the treatment of an acute migraine attack. The long time lag

of 5.5 hrs from GTN infusion to maximum migraine pain inten-

sity could indicate that NO initiate a slowly progressing patho-

logical reaction, that eventually will lead to a migraine attack.

We have found that after infusion of GTN the synthesis of in-

ducible NOS is upregulated in dura from rat. The maximal

amount of NOS is found 4-6 hrs after the GTN-infusion is ter-

minated, i.e. at the time when the migraine patients develop

the delayed headache (migraine attack). In the following stud-

ies we intend to illuminate changes in the expression also of

endothelial and neuronal nitric oxide synthase (NOS) in dura

and all the three NOS enzymes in cerebral blood vessels after

the infusion of GTN. Furthermore, we will investigate how in-

fusions of GTN involve changes in the sensitivity of cerebral

blood vessels to perivascular transmitters.

The results from the project will lead to an increased know-

ledge about which of the three different NOS enzymes that is

upregulated and where they are localized. Furthermore, we

will collect an increased understanding of the mechanisms

underlying an eventual hyper- or hyporeactivity of cerebral

blood vessels after GTN-infusion.

(Inger Jansen Olesen, Tina Zinck, Majid Sheykhzade, Trine

Meldgaard Lund, Uwe Reuter, Kirsten Busk)

Clinical and experimental micro array

investigations of mRNA expression during migraine

We have in a human model of migraine found a number of

substances that 5-7 hrs after an intravenous infusion trigger a

migraine attack. The key to the understanding of the outbreak

of the migraine attack lie in the mechanisms activated during

the infusion and that hour’s later lead to the migraine pain. If

several substances with different mechanisms of action initi-

ate a migraine attack, they must share a mechanism that is of

vital importance for the development of the migraine attack.

We have in a previous study shown that infusion of glyceryl-

trinitrate (GTN) in the rat results in an increased expression of

PAGE 90


Identification of peptides or peptide-like domains that

specifically interact with a protein-protein interface of

relevance for the modulation of blood clotting

We wish to identify small structures that interfere with the

binding of FVIIa to TF using page display technology. This will

be accomplished by searching for small peptides or small

peptide-like domains that utilize the same binding area that

are involved in the protein-protein interaction between FVIIa

and TF. The selection will include page displayed peptide li-

braries comprising both linearly and disulfide-constrained

peptides.

(Jan Engberg, Erik Riise, Liselotte Brix Jensen, Pernille Kops,

Rikke Claussen, Lars Harder Christensen, Rebecca Bach

Jensen and Espen Jannik Bjerrum)

(We collaborate with the groups of professor Lars Fugger,

Dept. of Clinical Immunology, Skejby Sygehus, professor

Jesper Zeuthen and ass. professor Lars Østergård Pedersen,

Dept. of Cell Biology and Cancer Research, The Danish

Cancer Society and research managers Lars Christian

Pedersen and Søren Bjørn, Novo Nordisk A/S)

VASCULAR PHARMACOLOGY

Studies of the effect of mental stress in rat on nitric

oxide synthase in dura and cerebral blood vessels

When patients are asked what triggers their episodes of mi-

graine, the majority of them nominate stress and it is well ac-

cepted that stress heighten the risk of migraine headaches.

The mechanisms underlying stress-induced migraine has still

not been investigated in detail and a possible explanation

could be a stress provoked increase in expression of en-

dothelial, inducible or neuronal NOS.

In this project we intend to illuminate changes in nitric oxide

synthase (NOS) expression in cerebral blood vessels and dura

after mental stress in rat. Furthermore we intend to investi-

gate if mental stress involve changes in sensitivity of cerebral

blood vessels to perivascular transmitters. The results from

the project will lead to an increased knowledge about which

iNOS mRNA in the dura, 2 and 4 hrs after termination of the

GTN infusion, and we have experimental evidence that this

enzyme is involved in migraine attacks.

The microarray technique allows quantifying gene-expres-

sion of thousand of individual mRNA transcripts simultane-

ously. We now plan to investigate the gene-expression after

infusion of a number of migraine provoking substances. The

study will be performed in migraine relevant tissues from rat,

as well as in leucocytes taken during a spontaneous migraine

attack and after experimentally triggered migraine in man. We

hope to be able to narrow the common denominators activat-

ed by all substances down to a few genes and hereby to

map out the genes that are activated in the beginning of a

migraine attack.

(Inger Jansen Olesen, Jes Olesen, Jens D Mikkelsen, Jesper

F Tvedskov, Kirsten Aagaard Busk)

Studies of the effect of feverfew and parthenolide

on nitric oxide synthase activity in cerebral arteries

and dura of guinea pig

Tanacetum parthenium(L) commonly known as feverfew is a

popular herbal remedy advocated for fever, arthritis and mi-

graine. The anti-migraine effect is mainly attributed to ses-

quiterpen lactones present in the plant. Parthenolide, the pre-

dominant sesquiterpen lactone in feverfew is regarded as the

most important of the biologically active substances isolated

from the plant. The exact mechanism by which feverfew and

parthenolide act in order to exhibit prophylactic anti-migraine

effect is still unknown. A number of recent studies indicate

that NO is a crucial molecule for the induction of migraine,

the present study is therefore designed to study the effect of

feverfew and parthenolide on enzymes catalyzing the forma-

tion of NO in cerebral arteries and dura.

(Inger Jansen Olesen, Per Mølgaard, Anne Adsersen, Trine

Meldgaard Lund, Majid Sheykhzade, Kirsten Aagaard Busk)

Signalling pathway for CGRP in isolated

resistance coronary arteries of rat

The intramyocardial resistance arteries regulate the coronary

perfusion. These arteries are densely innervated by sensory

nerve endings containing calcitonin gene-related peptide

(CGRP) and substance P. CGRP is a potent and powerful va-

sodilator, which is released during cardiac ischemia, and low

pH levels indicating an important role for CGRP in regulation

of coronary blood flow under ischemic conditions. The pur-

pose of our study was to investigate the mechanism of action

behind CGRP-induced relaxation in isolated rat intramural

coronary arteries.

Our results clearly demonstrate that CGRP relaxes precon-

tracted rat coronary arteries via three mechanisms: (1) a de-

crease in [Ca2+]i by inhibiting the Ca2+ influx through mem-

brane hyperpolarization mediated partly by activation of the

large conductance Ca2+- activated potassium channels, (2) a

decrease in [Ca2+]i presumably by sequestrating cytosolic

Ca2+ into thapsigargin-sensitive Ca2+ storage sites and (3) a

decrease in the Ca2+- sensitivity of the contractile apparatus.

In resting coronary arteries, however, there seems to be an

interplay between different types of K+ channels.

(Majid Sheykhzade in collaboration with Niels C. Berg Nyborg,

Novo Nordisk A/S)

MICROBIOLOGY

Microbiological control of pharmaceutical products

Pharmaceutical products for parenteral administration must

be free of pyrogens. Pharmaceutical preparations are tested

for pyrogens by the “Test for pyrogens” (rabbit pyrogen test)

or “Test for bacterial endotoxins” (LAL test). Both pyrogen

tests have limitations. Therefore we work towards alternative

in-vitro assays. The monocytic cell line Mono Mac 6 is being

evaluated for its use in detection of pyrogens in pharmaceuti-

cal preparation. In vivo monocytes play a key role in the fever

pathogenesis. When exposed to pyrogens they release cy-

tokines that mediate fever.

Like the rabbit pyrogen test, we have found that the Mono

Mac 6 cells are able to detect a broard spectum of pyrogenic

microorganisms. The cell culture assay is being optimized to

achieve a higher sensitivity to pyrogens.

Spores and vegetative bacteria of the gram-positive Bacillus

subtilis and the cell wall component lipotheicoic acid are able

to induce IL-6 in Mono Mac 6 cells. This makes the Mono

Mac 6 assay a usefull tool to study the thermostability of

these microorgansims and cell wall components.

The Mono Mac 6 assay is a valuable tool to test pharma-

ceutical products for pyrogenic contamination.

(Jens Juul Dencker Christensen, Erik Wind Hansen, Lise

Moesby, Janne Møgelhøj Colding, Helle Dyhrfjeld, Betina

Schøler)

Retroviral membrane fusion

The fusion protein of Moloney murine retrovirus is investigat-

ed. The fusion protein is a transmembrane protein. During

virus maturation a 16 amino acid peptide (the R peptide) is

cleaved of the cytoplasmic tail in order for the fusion protein

to gain activity. The R peptide has the sequence VLTQQY-

HQLKPIEYEP. We have previously found that the R peptide is

palmitoylated.

The R peptide is investigated by mutational analysis, fol-

lowed by transfection of the mutated viral genome into cells.

If the R peptide is totally truncated previous results show a

premature fusion (cell-cell fusion).

R peptide sequences (GenBank) of different murine retro-

virus were compared. The first ten amino acids are well con-


PAGE 91

served whereas the last amino acids varies largely and can be

deleted without serious consequences for the viral life cycle.

We have changed the lysine group (K) (to T or R) as it is a

candidate for the palmitoylation (amide binding). No biological

affects was observed, which either shows that the palmitoyl

group is not located here, or that that the palmitoylation does

not have biological effects.

Deletions in the well-conserved region were made (TQQY-

HQLK deletion, TQQY deletion, QYH deletion and HQLK

deletion). By transfection in cells these all give biological ef-

fects:

The TQQYHQLK deletion gives a premature fusion, does

not produce virus particles and is lethal for the cells. The

smaller deletions all give slight premature fusion, produce

virus particles, which though have a poor replication.

Analysis of protein cleavage is currently being investigated.

(Anne Zedeler, Randi Jensen, Klaus B. Andersen)

BIOACTIVE LIPIDS

Phospholipids are building blocks of the cell membranes, but

phospholipids are also precursors for extracellular and intra-

cellular signaling molecules that function as local hormones

(autocoids) and as second messengers, respectively. Some of

these bioactive lipids are formed from arachidonic acid, which

again is formed from the essential fatty acid linoleic acid. Fish

oils contains long-chain n-3 fatty acids, which can affect the

arachidonic acid metabolism, and the dietary content of n-3

fatty acids can thus affect different biological parameters.

Furthermore, dietary n-3 fatty acids are essential for the de-

velopment of the brain. Other bioactive lipids comprises dia-

cylglycerol, phosphatidic acid, platelet activating factor, lyso-

phosphatidic acid, ceramide, sphingosine-1-phosphate,

phosphatidylinositol 3,4,5-trisphosphate, 2-arachidonoyl-glyc-

erol, anandamide, and N-acyl-ethanolamines. We are current-

ly focusing on understanding the functions of N-acyl-ethanol-

amine phospholipids (NAPE) and of N-acyl-ethanolamines

(NAE) in the brain.

Biochemical characterization of the NAPE/NAE system

We are characterizing the enzymes involved in the formation

of NAPE (N-acyl-transferase) and in the formation of NAE

(NAPE-hydrolyzing phospholipase D). Furthermore, we are

studying the formation of these lipids in cultured neurons and

brain slices, and quantifying NAPE in tissue extracts by nega-

tiv ionisation electrospray mass spectrometer.

NAPE and NAE can be formed in cultured neurons exposed

to excitotoxic concentrations of glutamate or other com-

pounds that can induce cell injury. NAPE is believed to have a

membrane stabilizing effect, and NAPE is formed as a stress

response in cultured neurons and in rat brain in vivo. Some

molecular species of NAE, e.g. N-arachidonoyl-ethanolamine

(also called anandamide) and N-palmitoyl-ethanolamine are

ligands for different cannabinoid receptors, and these two

species of NAE have different biological effects. N-Arachidonoyl-

ethanolamine has the same biological effects as �9-tetra-

hydrocannabinol and N-palmitoyl-ethanolamine has antinoci-

ceptive and antiinflammatory effects. 2-Arachidonoyl-glycerol,

that can be formed during inositol phospholipid turnover, is

also a ligand for the cannabinoid receptors. 2-Arachidonoyl-

glycerol, anandamide and N-palmitoyl-ethanolamine are con-

sidered as endocannabinoids. Thus NAPE may be a neuronal

stress lipid and it is precursor for different endocannabinoids.

(Harald S. Hansen, Birthe Moesgaard, Henrik Hansen, Gitte

Petersen, Grete Sørensen, Jytte Palmgreen in collaboration

with Steen Honoré Hansen (Royal Danish School of Pharmacy),

J.J. Fernandéz-Ruiz (Complutense University, Spain), C.I

konomidou (Humboldt University, Tyskland), and H.H.O.

Schmid (University of Minnesota, USA))

NAPE and NAE in human brain tumors

We are quantifying in human brain tumours the activity of N-

acyltransferase, NAPE-hydrolysing phospholipase D, and

Fatty-Acid-Amide-Hyrdolase, three enzymes that take part in

the turnover of anandamide. Furthermore, we are also quanti-

fying different NAE molecular species. Anandamide and con-

geners may have a function in regulating the growth rate of

brain tumours.

(Harald S. Hansen, Birthe Moesgaard, Gitte Petersen, Jytte

Palmgren, Grete Sørensen in collaboration with M. Kosteljanets

and Helle Broholm (Danish State hospital), and H.H.O. Schmid

and P.C. Schmid (University of Minnesota, USA))

Dietary n-3 fatty acids and human brain development

Harald S. Hansen is engaged in a project on the importance

of dietary n-3 fatty acids for human brain development.

(In collaboration with L. Lauritzen and K.F. Michaelsen

Research Institute for Human Nutrition, Royal Danish

Agricultural and Veterinary University)


PAGE 92

SPHERE OF INTEREST

The Department of Social Pharmacy conducts research and

teaching within Social Pharmacy. The Department is also re-

sponsible for interdisciplinary teaching activities, including the

compulsory course on occupational health, the pharmacy in-

ternship and the new postgraduate specialisation programme

in community pharmacy.

Social Pharmacy may be defined as the discipline dealing

with the role of medicines at the level of the individual, group/

organisation and society. Social Pharmacy also embraces the

activities of the pharmaceutical profession. Hence, Social

Pharmacy spans a variety of themes from the experiences

and perceptions of the medicine user to national and interna-

tional drug policy.

Within Social Pharmacy theories and methods from the hu-

manities, the social sciences and natural sciences are applied

in a cross-disciplinary manner.

RESEARCH

The majority of the Department’s research is conducted in in-

terdisciplinary and inter-institutional project groups. Staff

members also participate in or co-ordinate international re-

search projects.

The Department’s research on ‘Medicine Use’ aims at im-

proving the rationality of medicine management and use

among professionals and among users. The goal of the re-

search in ‘Pharmacy practice’ is to support the development

of the pharmacists’ professional role and to evaluate pharma-

cy activities in health care.

TEACHING

Compulsory courses

The teaching of the Department includes the following

compulsory courses:

• Introductory Course (1st term) taught in collaboration

with other departments of The Royal Danish School of

Pharmacy

• Dissemination and Methodology in Social Pharmacy

(3rd term)

• Occupational Health (4th term)

• Social Pharmacy including Management & Organisation

(5th - 6th term)

• Pharmacoeconomics (6th term)

• Drug Dispensing and Customer Communication (7th term)

• Pharmacy Internship (8th term).

Elective courses

Within the period under review the Department taught the

following elective courses:

• Communication and Information

• Pharmacoeconomics

• Research Methods in Social Pharmacy

• Models for Technology Assessment in Health Care

• International Health Care.

POSTGRADUATE PROGRAMME

The Department offers two PhD courses with international

participation and with English as the course language:

‘Methodological Perspectives in Health Services Research’

and ‘Quantitative approaches to the evaluation of health care

inputs’. These courses were not taught in the period covered

by the report.

PAGE 94

Head of Department: Associate Professor Poul R. Kruse, DSc (pharm.)

Department ofSocial Pharmacy


Specialisation in Community Pharmacy

The Department is heavily involved in the co-operation be-

tween The Royal Danish School of Pharmacy and Pharmakon

a/s on the new specialisation programme in community phar-

macy. A fuller description of the new postgraduate pro-

gramme is given in a separate chapter, Specialisation in

Community Pharmacy, in the present report. The Specialisation

in Community Pharmacy programme is underway, and the

first Introductory Course was held on 5-9 April 2001 (Ellen

Westh Sørensen and Trine Hopp) and the Course in Health

Care Theory was held on 20-24 August and 20 November

2001 (Ellen Westh Sørensen and Thomas Clemens Jensen).

FKL – THE RESEARCH CENTRE FOR

QUALITY IN MEDICINE USE

The Research Centre for Quality in Medicine Use (FKL –

Forskningscenter for Kvalitetssikret Lægemiddelanvendelse)

was established in 1999. The overall objectives of the centre’s

projects are to provide scientific evidence to optimise the pro-

fessionals’ pharmacotherapy and the population’s medicine

use. In this way the research contributes to improved public

health and quality of life as well as improved economy of the

individual and society. The majority of the Department’s scien-

tific staff are involved in one or more centre projects. The

Centre is directed by Professor Ebba Holme Hansen of the

Department.

The Centre’s approach is multidisciplinary, inter-professional

and inter-institutional. The researchers involved in the Centre’s

activities represent several disciplines and institutions, includ-

ing Pharmakon, the Danish College of Pharmacy Practice, the

County of Vestsjælland, the County of Funen, the National

Institute of Public Health, Copenhagen University, the Univer-

sity of South Denmark, Aalborg University, the University

Hospitals Centre for Nursing and Care Research (UCSF) and

the Institute of Rational Pharmacotherapy. The 1991 Pharma-

cy Foundation has been the major external sponsor of the

Centre’s activities.

The Department’s involvement in FKL-projects is described

under ‘Projects’.

ARRANGEMENTS AND GUESTS

AT THE DEPARTMENT

From 20 September until 24 December 2000, Master’s thesis

students Christian Huyghe and Karen Hoebeke, Vrije

Universiteit Brussels, worked on their Master’s thesis

‘Qualitative and quantitative analysis of the asthma therapeu-

DEPARTMENT OF SOCIAL PHARMACY

Research seminar: ‘Strategies for Dissemination of Pharmaceutical Care Services’ 7-10 June 2001.

PAGE 95

tic outcomes monitoring (TOM) projects’ (advisor: Ellen Westh

Sørensen).

The Department arranged the yearly 2-day course for the

internship pharmacies January 15 to 16, 2001.

Approximately sixty supervisors from community pharmacies

and hospital pharmacies participated.

Professor Th F J Tromp, Groningen Universitet, visited the

Department 27 November 2000.

Dr. Ines Krass, University of Sydney, visited the Department

23 January 2001.

Charlie Benrimoj, Dean, Faculty of Pharmacy and Professor

of Pharmacy Practice, The University of Sydney, visited the

Department 29 January 2001

B.Pharm. (Hons) Mike Rouse from Zimbabwe, visited the

Department 16 May 2001.

Alison Roberts, Honour Thesis student, Faculty of Pharmacy,

The University of Sydney, Australia, studied at the Department

from 1 July until 21 December 2001

Ellen Westh Sørensen and Trine Hopp arranged a research

seminar: ‘Strategies for Dissemination of Pharmaceutical

Care Services’ 7-10 June 2001 at the Department of Social

Pharmacy. Participants in the meeting and presenters: Charlie

Benrimoj, University of Sydney, Alison Roberts, University of

Sydney, Parisa Aslani, University of Sydney, Hanne Herborg,

Division of Research and Development, Pharmakon, Miguel

Angel Gastelurruti, University of Granada, Ellen Westh

Sørensen and Trine Hopp.

Dr. Hans-Rüdiger Elster, Martin-Luther-University, Halle, vis-

ited the Department to discuss student exchange and mutual

research interests on 28 September 2001.

Parisa Aslani, BPharm (Hons), MSc PhD, MPS, MRPharmS,

The University of Sydney, visited the Department for a one

day meeting on 15 October 2001. Parisa Aslani made a pre-

sentation entitled ‘Consumer Opinions on Medicines

Information and Factors Affecting Use’. Trine Hopp and Alison

Roberts made a presentation entitled ‘Development of

Pharmacy Practice with special focus on implementation-pro-

cesses. Project status and theory thoughts’.

The Medicine Consultants Aase Nissen and Helle Neel

Jakobsen as well as Clinical Pharmacist Lisbeth Bregnhøj,

from Copenhagen County, presented their ongoing projects at

a departmental seminar on 17 December 2001.

The Department has hosted several meetings of the FKL –

Research Centre for Quality in Medicine Use throughout

the period of the report.

MEMBERSHIP OF EXTERNAL

BOARDS AND COMMITTEES

EXTERNAL PROFESSIONAL POSITIONS:

Ebba Holme Hansen

• President of the Danish Pharmaceutical Society (until

March 2001)

• Director of the Research Centre for Quality in Medicine Use

(FKL)

• Member of the Council of EUFEPS – European Federation

for the Pharmaceutical Sciences (until March 2001)

• Member of STAC – Scientific and Technical Advisory

Committee of the UNDP/World Bank/WHO Special

Programme for Research and Training in Tropical Disease

• Member of the International Task Force, American Society

of Consultant Pharmacists

• Member of the Project Co-ordinator Network ENRECA –

Enhancement of Research Capacity in Developing Countries

• External evaluator of NEPI, The Swedish National Network

for Pharmacoepidemiology (with Professor PMK Lunde,

Norway)

• Member of the evaluation panel for a professorship in so-

cial pharmacy at the University of Oslo

• Member of the evaluation panel for a professorship in so-

cial pharmacy/pharmaco-economics at the University of

Tromsø

• Member of the Advisory Committee to the Ministry of

Foreign Affairs on children’s and adolescents’ conditions in

developing countries

• Peer reviewer: Pharmacy World and Science, European

Journal of General Practice

• Member of the Editorial Board of Journal of Social and

Administrative Pharmacy

• Member of the Editorial Board of International Journal of

Pharmacy Education.

Trine Hopp

• Board Member of the Section for Social Pharmacy under

the Danish Pharmaceutical Society

• Member of the group ‘Quo Vadis 2000’, Astra-Zeneca

postgraduate training

• Member of Task Force Groups of The Association of

Danish Pharmacists.

Pia Knudsen

• Board Member of The Danish Society of

Pharmacoepidemiology.


PAGE 96

Laila Launsø

• Member of the National Board of Health’s Council on

Alternative Treatment

• Member of the Steering Committee of the Disease and

Society - International Network

• Member of the Board of The Danish Knowledge and

Research Centre of Alternative Treatment

• Chairperson of the Research and Knowledge Centre for

Unconventional Cancer Treatment

• Chairperson of the Centre for Bridgebuilding in Health Care

• Research Consultant for European Council for Classical

Homeopathy (ECCH)

• Member of the Treatment Board in the Danish Association

of Sclerosis

• Chairperson of a working group on developing a team of

conventional and unconventional therapists in relation to

treating patients having sclerosis, The Danish Association

of Sclerosis

• Member of the Board for Evaluation of a Homeopathic

Education for Health Professionals, Helsedepartementet,

Oslo

Ellen Westh Sørensen

• External Examiner, Tromsø University, Institute of Pharmacy

• Member of the Course Committee of the Specialisation in

Community Pharmacy

• Member of the Scientific Committee for the 12th

International Social Pharmacy Workshop 2002

• Member of the Supervision Group for the project The

Consultative Pharmacy, carried out by the Research and

Development Department at Pharmakon a/s

• Member of the Editorial Board of the International Journal

of Pharmacy Practice

• Member of the Committee for Postgraduate Training of

Pharmacists (PUF-A)

• Member of the board ‘Interdisciplinary Communication

Course, Copenhagen’

• Member of the Organising Committee for the Forum of

Health Care Research meeting October 2001.

Janine Morgall Traulsen

• Officially appointed external examiner for Engineering and

Social Studies

• Member of the Advisory Board: The Danish National

Institute for Medical Technology Assessment, Ministry of

Health

• Adjunct Professor – Mercer University Southern School of

Pharmacy.

GRANTS

Ebba Holme Hansen has received:

DKK 2.347 million (2000) and DKK 903,000 (2001) from The

Danish Ministry of Foreign Affairs towards the continued

implementation of a research education programme to devel-

op primary health care research in Nepal. In collaboration with

Department of Social Pharmacy; Department of Psychology

and Department of Public Health, University of Copenhagen;

DSI • Danish Institute for Health Services Research and

Development; Department of Epidemiology and Social

Medicine, University of Aarhus; and Tribhuvan University,

Kathmandu.

On behalf of FKL – Research Centre for Quality in Medicine

Use, Ebba Holme Hansen received a grant of DKK 2.5 million

from The 1991 Pharmacy Foundation for co-ordination and

administration and the following projects: The Pharmacy-

University Study, co-ordinated by Ellen Westh Sørensen and

Lotte Stig Haugbølle, and Improved Self-medication and Self-

care co-ordinated by MSc (pharm) Hanne Herborg (Pharma-

kon).

Erik Knudsen, Vestsjællands Amt, in collaboration with

Ebba Holme Hansen, has received DKK 200,000 (2000) and

DKK 338,500 (2001) from the Danish Medical Research

Council’s Regional Fund for Eastern Denmark for the FKL

project: The research foundation for intervention strategies to-

wards medicine prescribing and use. (The grant is adminis-

tered by Vestsjællands Amt).

Ebba Holme Hansen is member of the project group

‘Clinical pharmacist in primary health care’ co-ordinated by

Bente Kirkeby that has received a donation of DKK 700,000

from The 1991 Pharmacy Foundation. (The grant is admin-

istered by Frederiksborg Amt).

Claus Møldrup has received DKK 1,111 million from the

Centre for Evaluation and Health Technology Assessment,

The National Board of Health in support of a post-doc

study on pharmacogenomics.

Ellen Westh Sørensen received DKK 100,000 from The

Hørslev Foundation for the FKL project Pharmacy-University

Study for the period 2001-2002.

PROJECTS

MEDICINE USE

Intentions, Values, Rationales and

Strategies in GPs’ Prescribing

The knowledge assembled in the literature about GPs’ inten-

tions, values, rationales and strategies when prescribing

drugs is sparse. An understanding of the GPs’ perspective is


PAGE 97

essential in the attempt to develop primary care. The purpose

of this PhD project is to obtain an understanding of the reality

GPs face when prescribing drugs, from the GPs’ own per-

spective. In order to achieve this, participant observations

and semi-structured interviews are used. An approval from

the local ethics committee has been obtained. Twenty-four

GPs from the County of Vestsjælland have agreed to attend

the study. Both data collection and analysis are made after

the principles of Grounded Theory. The project will finish dur-

ing the spring of 2003.

The project is affiliated with FKL - Research Centre for

Quality in Medicine Use.

(Kristin Eskildsen. Supervised by Ebba Holme Hansen (main

supervisor) and Professor Uffe Juul Jensen, University of

Aarhus).

Prescribing of Antibiotics in Iceland

This project explores general practitioners’ views, reflections

and strategies when dealing with infections and prescribing

antibiotics. The project springs from a former PhD study at

the Department.

(Ebba Holme Hansen in collaboration with Ingunn Björnsdóttir,

CEO, PhD (pharm), and Almar Grímsson, MSc (pharm),

Iceland).

Behaviour of Rural Mothers in

Response to Diarrhoea in Children

Diarrhoea is one of the most common causes of child mortali-

ty in developing countries. Plenty of interventions have aimed

at disseminating and improving the use of ORS (Oral

Rehydration Salt) in relation to diarrhoea, however, without

sufficient success. This project aims at studying the user side

of the issue by exploring the mothers’ perceptions and views

re symptoms and treatment of diarrhoea in children. The pro-

ject springs from a Master’s of Social Pharmacy thesis.

(Ebba Holme Hansen in collaboration with Farai

Chinyanganya, MSc, PhD, United Kingdom).

Popular Attitudes to Medicines and Medicine Supply

The literature in the social sciences is scarce on how different

segments of the population view the benefit of medicines and

the medicine supply system. This project analysis the Danish

population’s perceptions of what constitutes a medicine and

attitudes and behaviours re the benefit of medicines and

herbal remedies, where they should be available, information

during the purchase situation, etc. The data were collected as

part of the Danish Health & Illness Survey year 2000 and cov-

ers large representative national samples of Danes. The sur-

vey provides the opportunity to relate data on the attitudes to

a number of population characteristics including illness,

medicine use, health care utilisation, and life style. The results

of the project will contribute to the user perspective on quality

management in the health care. Furthermore, there will be a

contribution to the development of policy in the drug arena.

The project is affiliated with FKL – Research Centre for


(Ebba Holme Hansen in collaboration with Niels Kr.

Rasmussen, National Institute of Public Health).

Medicine Use among Children and Adolescents

Medicine use is one of the domains studied in the WHO pro-

ject, Health Behaviour in School-Aged Children (HBSC). The

study comprises a series of cross-sectional school surveys of

national representative samples of girls and boys aged 11, 13

and 15. The project started in 1987. Twenty-eight countries

and more than 120,000 respondents participated in the 1998

survey. The study analyses the use of medicine in relation to

sex, age and country over time. Analyses include associa-

tions between medicine use and symptoms, social status,

psychosocial conditions and social network.



(Ebba Holme Hansen in co-operation with the national co-or-

dinators for the HBSC project: Bjørn Holstein and Pernille

Due, Institute of Public Health, Copenhagen University, and

the international HBSC Co-ordinator Candace Currie,

University of Edinburgh).

TUPP – The User Perspective on Psychotropic Drugs

TUPP was initiated by the European Drug Utilisation Research

Group, formulating the need for qualitative pan-European re-

search on medicine use. The overall objective of the project is

to explore the social meanings attached to the use of psy-

chotropic medicines at different locations in Europe. The core

project is based on qualitative in-depth interviews with at

least 20 informants in each country. As the consumption of

SSRIs is increasing rapidly all over Europe, the study of these

medicines is mandatory for each research group. A multidisci-

plinary project group with participants from 11 countries and

13 research groups has been established.

The Danish sub-studies are affiliated with The Research

Centre for Quality in Medicine Use.

(Ebba Holme Hansen, Project Co-ordinator, Søren Troels

Christensen, Kristin Eskildsen, Stig Helweg-Jørgensen and

Pia Knudsen in co-operation with approximately 25 re-

searchers from European countries and WHO EURO,

Pharmaceuticals Programme).

Danish sub-studies:

Psychotropic Drug Dependency in a User Perspective

This project explores the users’ experiences, reflections and

strategies in relation to long-term use and being dependent

on psychotropic drugs. The analyses are based on 50 in-


PAGE 98

depth, semi-structured interviews with people with a self-di-

agnosed dependence on benzodiazepines, primarily.

(Ebba Holme Hansen and Stig Helweg-Jørgensen).

Young Women’s Use of SSRIs

The objective of this PhD study is to contribute to an under-

standing of the use of SSRIs among younger women by ad-

dressing the users' subjective experiences. The empirical

foundation of the project consists of Danish women aged 18

to 34 with SSRI prescriptions. The women were identified

through pharmacies located in the Copenhagen area. A total

of twelve in-depth interviews including six re-interviews were

conducted.

It can be concluded that the users of SSRIs relate the use

of the medicine not so much to clinical conditions as to social

meanings. It can further be concluded that the use of SSRIs

is related to ambivalent feelings. The medicine is experienced

as a helper that enables the users to regain their social func-

tioning, and at the same time as a labelling agent. This study

showed that the use of SSRIs has more implications than just

controlling the illness. The use of SSRIs has social meanings.

It stigmatises the users, and it has an effect on the users’

self-concept.

The study is linked to TUPP - The User Perspective on

Psychotropic Drugs and to FKL - Research Centre for Quality

in Medicine Use.

(Pia Knudsen supervised by Ebba Holme Hansen (main su-

pervisor) and Janine Morgall Traulsen).

Enhancement of Research Capacity in Nepal:

A Primary Health Care Project

The background for this Danida sponsored project is partly

the Nepalese research system’s lack of competence and ca-

pacity in terms of primary health care, including drug use, and

partly the widespread problems that characterise Nepalese

health care in relation to an overwhelming morbidity level and

an extremely poorly functioning health care. The project

therefore has two main goals.

- To strengthen the research competence at university level in

Nepal through the accomplishment of research courses and

education up to PhD level.

- To focus PhD projects towards primary health care in Nepal,

and to use the results directly as a part of the Nepalese

health policy and in health care practice.

The objective of the project is to integrate two parallel pro-

cesses of development namely a researcher training pro-

gramme and an inter-disciplinary research programme, that

has primary health care as its research agenda.

The PhD studies carried out with the Department deal with

the projects: Quality Assessment of a Health Care Information

System: A Case Study from Nepal (Sharad Onta), Assessing

the Quality of the Provision of Antibacterials in the Nepalese

Health Care System (Shiba Karkee), and A User Perspective

on Tuberculosis Treatment (Pranaya Mishra).

(Ebba Holme Hansen (Project Co-ordinator), Ib Bygbjerg,

Institute of Public Health, University of Copenhagen, Rolf

Kuschel, Department of Psychology, University of Copen-

hagen, and Svend Sabroe, Department of Epidemiology and

Social Medicine, University of Aarhus. The Nepalese counter-

parts are the following professors from the Tribhuvan Univer-

sity, Kathmandu: Mathura P Shrestha, Kumud K Kafle,

Rishikeshab R Regmi, and Ayan B Shrestha. The project is

associated to the Danish ENRECA programme (Enhancement

of Research Capacity in Developing Countries)).

Health Interview Surveys in Europe (EuroHIS); Medicine Use

EuroHIS is a WHO co-ordinated European project aiming at

the development of standardised questionnaires to be used in

national and cross-national health surveys. In this sub-study

nationally used questionnaires dealing with medicine use are

collected and reviewed. Based on the findings, a battery of

questions are developed and validated to form the basis for

future national and international surveys. Researchers from

five countries and the WHO participate in the medicine use

project. The collaborative work is funded by a BIOMED grant

from the EU.

(Ebba Holme Hansen in co-operation with researchers from

Finland, Greece, Israel and WHO EURO).


Prevalence of

symptom related

medicine use dur-

ing the past month

among 15-year-old

Danes (percentage

of respondents).

Medicine for headache, 15-year-olds:

Medicine for stomacache, 15-year-olds:

PAGE 99

CEEMedicines

This project aims at mapping and analysing the medicine

markets in Eastern European countries. Data on registered

medicines on the market in each country are collected. The

project is financially supported by the EU and co-ordinated by

Dr. Pietro Folino-Gallo, Università Cattolica del Sacro Cuore,

Rome.

(Ebba Holme Hansen in co-operation with researchers and

medicine regulators from ten countries and WHO EURO,

Pharmaceuticals Programme).

Social Determinants of Medicine Use

in the Danish Population

The aim of this study is to characterise the medicine use of

the Danish population with special focus on social inequality.

The analyses use data from The Danish Health and Illness

Survey 2000 conducted by the National Institute of Public

Health. This interview survey of the population contains social

and demographic background information as well as informa-

tion on health and illness behaviour and self-reported use of

medicine. The analyses will include multivariate analyses and

different therapeutic groups of medicine.



(Merete W. Nielsen, PhD student, is supervised by Ebba

Holme Hansen (main supervisor) and Niels Kristian

Rasmussen, National Institute of Public Health).

The Practices of Dispensing and

Non-Dispensing Doctors

The number of dispensing doctors has increased world-wide

in recent years. What are the implications of this trend, what

are the consequences for the quality of medicine therapy?

This PhD project aims at evaluating and comparing the pre-

scribing practices of dispensing and non-dispensing doctors

and to assess the quality of dispensing doctors’ pharmacy

practices. Data have been collected.

(Birna Trap, PhD student, MSc (pharm), BCom, under the

supervision of Ebba Holme Hansen (main supervisor), Hans

Hogerzeil, WHO HQ/Geneva, and Charles Todd, University of

Zimbabwe).

A User-evaluation of Treatment with Conventional

Drug Therapy and Classic Homeopathic Treatment

Concerning Allergy and Asthma

(Laila Launsø and Charlotte Grum, MSc, Psychologist;

Henriette Brender, BA, Centre of Bridgebuilding in Health

Care, Copenhagen; Anne Hvenegaard, MSc, Project

Manager, DSI, Institute for Health Care, Copenhagen.

Cooperation with Vinjar Fønnebø, MD, Professor and Director

of Research Centre in Alternative Medicine, University of

Tromsø, Norway)

The Development of Drug Therapy in Denmark

The project is a historical analysis of the factors, including reli-

gious, philosophical, scientific, technological and legal as-

pects, which have determined the development of drug thera-

py in Denmark since the introduction of the concept of autho-

rized drugs in the 17th century.

(Poul R. Kruse).

Cancer Patients’ Use and Assessment

of Herbal Medicine

A survey study on 395 cancer patients’ patterns of usage of

herbal medicine is conducted. The primary aim of the project

is to establish a database to which cancer patients and thera-

pists have access.

(Laila Launsø and The Research and Knowledge Centre for

Unconventional Cancer Treatment: Helle Andersen, MSc;

Louise Rønnov, BA; Henrik Langgaard MD)

Social, Ethical and Legal Aspects

of Pharmacogenomics

This research project focuses on pharmacogenetics and

pharmacogenomics as a research strategy for future drug re-

search and development. The aim of the project is to investi-

gate the pros and cons of pharmacogenomics in a post-mar-

keting perspective with focus on the social, ethical and legal

dimension.

(Claus Møldrup)

Evaluation of a New Drug Distribution Legislation

in Iceland – a European Laboratory

A new drug distribution law took effect in Iceland in 1996.

The main thrust in this legislation is the right of all registered

pharmacists to open one pharmacy each and the abolish-

ment of the drug price regulation by the government and

abatement of the strict rules governing drug advertising to the

public. A multi-study evaluation of the effects of the change in

legislation was initiated in 1995. Various research methods

were employed, including focus group interviews with users

of pharmacy services, interrupted time series analyses of eco-

nomic and drug utilisation data, and focus group and one-on-

one interviews with pharmacists. Data collection and analysis

was completed in 1999. In 2000 and 2001 the results of this

evaluation were prepared in the form of articles.

(Janine Morgall Traulsen, Anna Birna Almarsdóttir, Iceland,

Almar Grímsson, Iceland, and Ingunn Björnsdóttir, Iceland)

The New Medicine Consumer

The goal of this project is to investigate social and economic

trends, which are currently affecting medicine users – attitudes,

knowledge and action. The project focuses on theory devel-

opment as well as data collection. A literature review began

at the end of 2001. The empirical part of the study is being


PAGE 100

planned and will include individual interviews and focus group

interviews. Janine Traulsen received a "research stipend" from

DFH beginning September 2001 to develop this project. From

1st October 2001 a PhD student, Bertel Rüdinger, joined the

project).



(Janine Morgall Traulsen).

Popular Beliefs about Medicine

Eight focus group interviews were carried out in urban and

rural Iceland to answer the research question – What are the

hopes and fears of the lay public in Iceland with regard to

pharmaceutical R & D including issues pertaining to the

Health Care Database? Iceland was chosen to study this

phenomenon in the wake of the public debate about the

Icelandic Health Care Database (the aim is to code medical,

genealogical and genotypical information on the entire popu-

lation). The project consists of a literature review, theory build-

ing and focus group interviews followed by individual inter-

views. Data collection took place in 2001 and analysis and re-

port writing will take place in the first half of 2002.

(Responsibility for carrying out the project lies with a project

group: Janine Morgall Traulsen, Ingunn Björnsdóttir (principal

investigator), Iceland, and Anna Birna Almarsdóttir, Iceland).

PHARMACY PRACTICE

The Distribution of Medicine in Denmark

– in the Light of Deregulation

On 30 May 2001 the members of the Danish Parliament

agreed to deregulate the distribution of medicine to the pub-

lic. The main change is that a wide range of OTC-medicine

(e.g. painkillers and laxatives) can be sold outside pharmacies

beginning 1 October 2001. In the future OTC-medicine will

become part of the normal sale of convenience goods. The

deregulation is a climax of many years of ongoing discussions

concerning how to regulate the distribution of medicine in

Denmark. Having in mind the general advance of market ori-

entated health reforms in western societies one could won-

der: Why has the Danish pharmacy sector not been subject

to deregulation before? And why only deregulate the sale of

OTC-medicine? The PhD project will contribute with know-

ledge of the mechanisms that influence policy processes in

this area.



(Jakob Bjerg Larsen supervised by Janine Morgall (main su-

pervisor), Poul R. Kruse and Assistant Professor, MSc (pol

sci), PhD Karsten Vrangbæk, Department of Political Science

and Institute of Public Health, University of Copenhagen).

Pharmaceutical Care in Denmark

In Denmark and internationally, the structure of medicine sup-

ply has been discussed during the past 30 years. The role of

the community pharmacist has been a focal point of this dis-

cussion. Pharmaceutical Care has been one of the strategies

used to ensure a professional role for the pharmacist in the

future. The aim of this PhD project is to analyse the founda-

tion for and implementation of Pharmaceutical Care in Danish

community pharmacies. Empirical data have been collected

by a postal questionnaire involving all Danish pharmacies.



(Charlotte Rossing supervised by Ebba Holme Hansen (main

supervisor) and Janine Morgall Traulsen).

Professional Development of Pharmacy Practice

– with special focus on implementation processes

There are different traditions for carrying out intervention re-

search in the various professional groups. Descriptive and ef-

fectiveness studies dominate. The overall purpose of this PhD

project is to describe and understand the relationships that

influence the implementation process of professional interven-

tions within pharmacy practice in Denmark. The study is car-

ried out from an organisational perspective. This perspective

is necessary in order to follow and analyse the intervention

process and in order to understand possible reasons for

problems in relation to implementation.

The PhD project is part of a bigger international project with

the overall aim ‘Development of strategies for dissemination

of pharmaceutical care services’. Through collaboration with

PhD student Alison Roberts, University of Sydney, the de-

scriptions and understandings of the relationships that influ-

ence the implementation process will be achieved through

quantitative studies as well as qualitative studies.



(Trine Hopp under the supervision of Ellen Westh Sørensen

(main supervisor), MSc (pharm) Hanne Herborg, Pharmakon,

and Dr. PH Lis Wagner, UCSF. The international project group

includes from the University of Sydney, Australia: PhD student

Alison Roberts under the supervision of Professor Shalom

(Charlie) Benrimoj (main supervisor), Parisa Aslani, Lecturer;

Tim Chen, Lecturer; and Kylie Williams, Lecturer).

The Pharmacy-University Study - an action

research project involving the pharmacy, pharmacy

students and researchers in pharmacy practice

The project is carried out in co-operation between re-

searchers from the Department of Social Pharmacy, re-

searchers from Pharmakon, supervisors in the pharmacies

and pharmacy students during their internship in the pharma-

cies. The project was initiated in 1998 has run for a three-


PAGE 101

year period, first year involving the angina pectoris patients,

second year type 2-diabetes patients, third year asthma pa-

tients. The overall purpose of the project is to contribute to

quality development of pharmacy practice and pharmacy

practice research in the area of pharmaceutical care. The

aims of the project are threefold:

• to form the basis of an improvement of the pharmacy’s ad-

vice to patient groups, based on the user perspective, and

to contribute to a basis for decisions for the individual phar-

macy’s policy concerning the patient group

• to develop and test participatory action research as a way

of developing pharmacy practice

• to support the pharmacy students during their internship in

pharmacy work with pharmaceutical care, achieve a good

understanding of the user perspective and get experience

in pharmacy practice research.

During 1999, 2000 and 2001, data have been collected in the

form of interviews with the following patient groups: angina

pectoris patients (123), type 2 diabetes patients (176) and

asthma patients (80). At the same time, through question-

naires, the pharmacy staff has brought out their knowledge

and desire for information concerning the same patient

groups. In 1999, 2000 and 2001, results from the patient in-

terviews and the staff questionnaires were presented to the

staff of the participating pharmacies (1999: 40 pharmacies,

2000: 50 pharmacies, 2001: 28 pharmacies), and the current

activities of the pharmacies were recorded. The activities in

the pharmacies, from all the three years, will be evaluated.

Internship students have been responsible for the interviews

and the organization of tasks on the premises of the partici-

pating pharmacies. The materials of the project can be found

on the internet www.dfh.dk/dfh-apotek/.

Part two (2001-)

The results from the three patient groups uncovered a great

quantity of drug related problems. Therefore, the project

group has decided to carry out a new phase of the project

(second phase). The objective of the second phase is dis-

semination of the results, in an easily accessible form, to the

interested parties in the health sector (patient associations,

pharmacies, MDs, outpatients’ clinics, the counties pharma-

ceutical consultants) as a contribution to their work with im-

proved medicine use to these selected patient groups.



(Ellen Westh Sørensen and Lotte Stig Haugbølle in co-opera-

tion with Anette Mühring, Hørsholm Apotek; Birgitte

Gundersen, Delfin Apoteket; Hanne Herborg, Pharmakon A/S;

Hanne Lindegren, Ringsted Apotek; Karen Aarestrup

Johansen, The Danish Pharmaceutical Association; Kirsten

Holme Petersen, Pharmakon A/S; Kirsten Laursen, Ørne

Apoteket; Kirsten Lindholm, Centralapoteket, Fyns Amt; Lene

Lorentzen, Frederiksværk Apotek; Linda Larsen, Pharmakon

A/S; Liselotte Winther, Hvalsø Apotek; Thomas Clemens

Jensen, The Royal Danish School of Pharmacy; Trine Toft,

Sygehusapoteket, Vestsjællands Amt; Ulla Ander-sen,

Apoteket Rosen; and pharmacy students from The Royal

Danish School of Pharmacy Camilla Suensen, Eva Awad, Ida

Jensen and Søren Holm-Møller).

Improved Self-medication and Self-care

The objectives of the project are: 1) To develop and imple-

ment service for systematic counselling on self-care and self-

medication in community pharmacies aimed at empowering

users to make decisions and solve problems in order to ob-

tain better quality of life. 2) To develop a model for a con-

trolled study aimed at documenting the outcomes of the ser-

vice and testing the instruments for data collection.

The pilot study was completed in 2001, and the main study

has started. The project is part of an international research

co-operation, Pharmaceutical Care Network Europe (PCNE).

In Denmark, a preliminary study is carried out where the inter-

vention is developed and tested.



(Project Manager: Hanne Herborg, Pharmakon. Other mem-

bers of the project group: Ellen Westh Sørensen; Steffen

Jarlov, GP; Bertil Marklund, Med.Dr. Project Co-ordinators:

Birthe Søndergaard, Bente Frøkjær, Dor-the Tomsen and

Dorte Glintborg Nielsen).

ARTFARM. Nordic Database for Studies

and Projects within Pharmacy Practice

The objective is to procure relevant Nordic scientific studies

for practitioners and students of pharmacy practice. The main

goal is to be an incentive to research on pharmacy practice.

www.dfh.dk/artfarm.The project is supported financially by

the Danish Pharmaceutical Association.

(Ellen Westh Sørensen in co-operation with Inger Duus

Nielsen, MSc (pharm) and Karen Aarestrup Johansen, MSc

(pharm), Danmarks Apotekerforening; Kirsten Holme Petersen

MSc (pharm) Pharmakon; Susanne l. Weng, MSc (pharm),

Hirtshals Apotek).

Intervention in Pharmacy

– a Case Study about the Implementation

of Pharmaceutical Care at Brønshøj Apotek

The development and implementation of pharmaceutical care

in a community pharmacy has been followed over a period of

2-3 years. The proprietor, the staff and a research consultant

have developed ‘tools’ for the implementation of pharmaceu-

tical care in community pharmacy. The development- and im-

plementation process has been followed. The theoretical ba-

sis is organisation theory. The design is participatory action

research and formative evaluation. Data collection methods


PAGE 102

PhD students Trine

Hopp, of the

Department, and

Alison Roberts,

University of

Sydney, analysing

their pilot study:

Development of

Health Care

Services in

Pharmacy Practice.

were interviews of staff and research consultant and docu-

ments from the pharmacy. The change strategy and the barri-

ers and facilitators for the development and implementation of

the new practice is described.

(Ellen Westh Sørensen in co-operation with Research

Consultant Liselotte Winther, Pharmakon, and Pharmacy

Proprietor Inge Børsting and staff at Brønshøj Apotek).

OTHER PROJECTS

A User-evaluation of Medicine, TCM Acupuncture and

Nutrition Therapy concerning Patients having Bronchial

Infections/Symptoms

(Laila Launsø and Eva Brendstrup, MSc, Centre of Bridge-

building in Health Care, Copenhagen).

Bridgebuilding in Health Care

A concept for bridgebuilding in health care between pharma-

cists, physicians and alternative therapists has been devel-

oped including research projects. The focus has been on

conceptualising the practitioners’ treatment models consisting

of four components: disease/health theories; diagnostic sys-

tems; treatment methods and expected and experienced out-

comes. The results are used in relation to seminars focusing

on building dialogues and co-working between conventional

health care groups and alternative therapists.

(Laila Launsø and therapists and researchers from Centre for

Bridgebuilding in Health Care and from The Research and

Knowledge Centre for Unconventional Cancer Treatment and

senior students from University of Roskilde, University of

Copenhagen and Department of Social Pharmacy, The Royal

Danish School of Pharmacy).

Physicians and Pharmacists

Practising Unconventional Treatment

A study has been conducted on 20 physicians’ and pharma-

cists’ motives for education and practice in unconventional

treatments, their experiences from practising both conven-

tional and unconventional treatments and their experience

with reactions from professional colleagues.

(Laila Launsø).

A User-evaluation of Unconventional

and Conventional Cancer Treatment

(Laila Launsø and Henrik Langgaard, MD; Charlotte Kira

Kimby, MSc; Louise Rønnov, BA, The Research and

Knowledge Centre for Unconventional Cancer Treatment;

Inge Henningsen, MSc, Associate Professor, Department of

Statistics, University of Copenhagen).

Evaluation of Community Involvement

in Schistosomiasis Control

More than 200 million people worldwide are affected with

Schistosomiasis, a debilitating long lasting tropical disease. In

Zimbabwe, a community participation project has utilised the

dried berries from a locally grown plant as molluscicide. The

plant is Phytolacca dodecandra - locally called Gopo. The

present PhD project has evaluated the above community par-

ticipation project by analysing attitudes, behaviours and

knowledge as well as learning, gender and power issues.

(Addmore Ndeka, PhD, MA (Sociol). Supervisors: Ebba

Holme Hansen (main supervisor), Per Mølgaard, Department

of Medicinal Chemistry, Peter Furu, Danish Bilharziasis

Laboratory, and Dr. Godfrey Woelk, University of Zimbabwe).


PAGE 103

The DanishPharmaceutical Library

THE LIBRARY

The aim of the Library is to support research and education

at the Royal Danish School of Pharmacy and serve the needs

of the School's staff and students. Part of the national net-

work of research libraries, it is open to the public and invites

all interested users to benefit from its traditional and electronic

collections.

The Library provides training and guidance in the use of its

services and how to seek information in the school's net-

worked databases and on the Internet.

The Information Officer is attached to the library’s admini-

stration.

ACTIVITIES AND PROJECTS

The library board and library staff have thoroughly discussed

and evaluated the library’s service profiles and strategies

through 2001.

During the period September 2000 - December 2001, the

library has improved its range of services and information

about the services. Transformation to the electronic library is

actively underway e.g. downloading full-text articles from the

library’s range of electronic journals reached 21,000 articles,

an increase of 100% from December 2000 to December

2001. Students and researchers have the benefit of direct

reservation and request of copies or books through the li-

brary’s OPAC. Interlibrary loan requests are received by e-mail

or the facilities in bibliotek.dk.

Many tests of electronic databases and reference works are

facilitated through the home page of the library: Internet edi-

tion of the Combined Chemical Dictionary, Nature full-text edi-

tion, Pharma-Transfer, Landolt-Börnstein, Encyclopaedia Bri-

tannica - just to mention a few.

The library’s home page was expanded and improved

through autumn 2001. It now provides access to an automat-

ically generated list of new books; LIST-FARM - a holding list

of printed journals in the library; an automatically generated

alphabetical list with links to the electronic journals the library

subscribes to; an annotated web-guide; help-sheets to ac-

cessible databases and much more.

The user survey made it clear that an increase in opening

hours was necessary. The library extended the opening hours

by 4 hours every week starting September 2001.

The merging of the Dictionary of Organic Compounds,

Dictionary of Natural Products and other electronic dictionar-

ies made the library upgrade its access to the networked edi-

tion called the Combined Chemical Dictionary November

2000. The upgrade ensures direct access to information from

laboratories and classrooms.

In December 2000 the library took out an Internet subscrip-

tion to the citation database Web of Science and from

January 2001 access was opened to Science Direct, ensur-

ing access to approx. 1200 electronic journal titles from

Elsevier.

The library system ALEPH was upgraded September 2000,

which gave rise to a good deal of trouble for both library staff

and library users.

Also in 2001 the Danish Pharmaceutical Library participated

actively in several projects concerning "Denmark’s Electronic

Research Library" (DEF), e.g. the library is still part of the pro-

ject to convert the old card catalogues to electronic media.

From August 2000 Alice Nørhede headed a DEF project in-

cluding four other libraries to develop a user survey based on

the international accepted model for European Customer

Satisfaction Index (ECSI). In February 2001 the questionnaire

was distributed to the users of the five libraries and in summer

2001 the results were presented to the board of DEF.

The project generated interest as well as appreciation from

the library society. A report is available on:

http://www.dfh.dk/bibliotek/brugertilfredshed_rapport.php3e


PAGE 104

Head of Library Services: Alice Nørhede

Facilities of DADS (Denmark Article Database Service) - a

gateway to electronic journals used intensively by in-house

researchers and students - was much improved in the begin-

ning of 2001. Unfortunately, the library had to terminate ac-

cess in December 2001 due to a 100% increase of the sub-

scription price to the system. Termination started a flood of

protests from researchers and students at the Royal Danish

School of Pharmacy, but there does not appear to be a solu-

tion at this time.

Approx. 35,000 visits were paid to the library from January

2001 to December 2001.

TEACHING AND GUIDANCE

Study Start programme: Since the start of a new structure for

the Study Start programme in 1998, the library has participat-

ed in introduction courses for new students. In September

2000 and 2001 the library offered all new students a lecture

on how to use electronic services in the Danish library sys-

tem, a hands-on lecture on using the Internet for information

retrieval and a tour of the library – presented in 2001 in the

guise of a treasure hunt. Students then carried out compulso-

ry exercises. Both students and library staff evaluate this

training every year and every evaluation results in further ad-

justment and updating of the programme presented.

The library participates in teaching the compulsory course

in "Organic Synthesis" during the second term and presents

the printed versions of Chemical Abstract and Beilstein and

the electronic version Crossfire/Beilstein.

In autumn and spring optional courses are run for staff and

students in the use of MEDLINE, IPA, and Analytical

Abstracts. Approximately 30 participants attend these cours-

es every term. As many services are now offered through

FARM-base - the Library’s OPAC – an introduction to FARM is

arranged for the staff every term.

A new initiative in September 2001 was participation in the

compulsory course "Social Pharmacy including Management

& Organisation" (5th term). It was arranged as a classroom

demonstration encouraging students to use electronic ser-

vices available on the school’s Intranet and on the Internet.

Continuing and postgraduate education: In January 2001,

the Department of Social Pharmacy arranged a postgraduate

course for student pharmacy advisors. The library contributed

a course entitled: Searching for information in the physical

and electronic library.

In connection with Danmarks

Farmaceutiske Selskabs Sektion for

Klinisk Farmacis (The Danish

Pharmaceutical Society – Section

for Clinical Pharmacy) course in

spring 2001, the research librarian

taught techniques for seeking infor-

mation on the Internet.

In summer 2001 the library par-

ticipated in a course for students

entitled "Specialist Education of

Pharmacy Practice".

Every January and October the

library offers a course to PhD stu-

dents: "Bibliographic Software.

Hands-on Use of the Reference

Manager." The course attracts

about 10 participants every time.

Alice Nørhede lectured at the

Royal School of Librarianship and Information Sciences for

fourth-term students as well as at two continuing education

courses in autumn 2000 and summer 2001. She also made a

presentation to the members of the Danish Librarians’ Group

for Medical Information in March 2001. All presentations fo-

cused on the theme: "Finding pharmaceutical information on

the Internet".

EVENTS, VISITS AND MEETINGS

November 2000 12 library students visited the Danish Phar-

maceutical Library. They attended a lecture held by Alice

Nørhede, presenting the library and its activities in the context

of the organisational, educational and economic conditions.

Later this winter, two library students visited the library and

interviewed the research librarian about the reference services.

Spring 2001 two colleagues from the library of Kann

Rasmussen (Velux) visited our library.

December 2001 two senior scientists from the Institute of

Pharmacology in Oslo visited the library to study the historical

collection of the library.

THE DANISH PHARMACEUTICAL L IBRARY

PAGE 105

January 2001 Alice Nørhede was twice a member on a

panel debating "The practical project" – part of the librarian

degree offered by The Royal School of Librarianship and

Information Science.

Alice Nørhede gave a lecture about the results of the li-

brary’s user survey DEF project called: "User satisfaction in the

electronic library" at the Nordic Summer School, The Royal

School of Librarianship and Information Sciences, July 2001.

Alice Nørhede made a presentation of the same project at

the official opening of the "DEF portal", September 2001.

MEMBERSHIP OF EXTERNAL ORGANISATIONS

AND COMMITTEES

Alice Nørhede

• Chairman of De Små Chefers Forum - an organisation of

approx. 200 smaller Danish research and special libraries

until August 2001. She is still a member of the Board.

• Appointed member of Biblioteksrådet (Library Council) an

advisory body for the Danish National Library Authority, until

August 2001.

• Second vice-president on the EAHIL Board (European

Association for Health Information and Libraries), until

January 2001.

• Member of The Danish Librarians' Group for Medical

Information.

• Member of a working group autumn 2000 at the Royal

School of Library and Information Services planning the end

of the Librarian degree programme as a practical project

analysing a concrete library-related issue.

• Appointed member to a committee by the Danish National

Authority until August 2001 dealing with superstructure and

information supply of the council libraries.

• Member from December 2001 of a working group dealing

with research library statistics.

Martin Weile

• Appointed member of the Danish Bibliographic Centre

Netpunkt working group 2001.

GRANTS

In the summer of 2001, the Library received a donation from

Apoteker J.B. Mikkelsens og hustru Kgl. translatrice

Gudrun Mikkelsens Farmaceutiske Fond. The donation

was used to buy software and books.

In the summer of 2001, the Library received a donation

from Apotekerfonden af 1991. The grant was used to buy

books for students taking the Specialist Education of

Pharmacy Practice.

See the Internet for more information about the library and

its activities.

The website of the Danish Pharmaceutical Library

www.dfh.dk/bibliotek

FARM (The Library's OPAC) http://dfb.dnlb.dk:8020/ALEPH

Danmarks Elektroniske Forskningsbibliotek www.deff.dk/

THE INFORMATION OFFICER

Jesper Munck, the information officer, is the editor of Plexus –

the official magazine issued by The Royal Danish School of

Pharmacy. Plexus was published in its current form for the

first time in 1999/2000 and is intended for employees and

students, as well as the pharmaceutical world outside the

School to some extent. Since its relaunch in 1999, both the

size and circulation of the publication have increased 20%. In

2000 Plexus began cooperating with De Danske Studieblade,

which handles advertising sales for seven Danish magazines

representing university institutions.

The information officer is a member of the editorial commit-

tee of Lægemiddelforsknings [Drug Research], a popular sci-

entific journal that publishes the results of the research con-

ducted by the Royal Danish School of Pharmacy and associ-

ated research centres.

The magazine is extremely popular with its the target group,

upper secondary chemistry and biology teachers, who re-

ceive the magazine free of charge every year.

A new recruitment website (www.dfh.dk/farmaceut) target-

ed at potential students was launched in February 2001. The

site is a team effort by the information officer along with MSc

Henrik Fylking Nielsen (Novo Nordisk) and Lærke Vester-

Andersen, study guide officer from the Course Administration.

In August 2001 a new webmaster, Henrik Korzen, joined

the School staff. He works together with the information offi-

cer to present the news and services, general content and

graphics for the School’s website.

Together with the registrar, study supervisors, PhD adminis-

tration and information committee, the information officer was

responsible for PR activities in conjunction with the School’s

Open House Day. The same team also put together the enrol-

ment materials – The pharmacist is the drug expert – and a

series of presentations focusing on the pharmacy degree pro-

gramme and its potential, and requirements for enrolment.

The information officer is the official contact person for the

press and other external bodies and he answers -or organis-

es responses to enquiries to the School.

MEMBERSHIP OF EXTERNAL ORGANISATIONS

AND COMMITTEES

Jesper Munck is a:

• Member of EUPRIO (European Universities Public Relations

and Information Officers Association)


PAGE 106

• Member of NUAS-Informatörsektion (NUAS: The Nordic

Universities’ information co-operation)

• Member of the Danish universities’ information employees

group

• Member of Danske Videnskabsjournalister (Danish

Scientific Journalists)

• Specialist contact person for Aktuel Naturvidenskab

(Modern Science)

THE DANISH PHARMACEUTICAL L IBRARY

PAGE 107

Well aware of the increased competition for potential students, the Royal Danish School of Pharmacy advertised in Danish me-

dia twice during 2001. In March the School released a poster, The pharmacist is the drug expert, and followed up a month later

with an advertisement in the magazine Chili headlined: Get high on pharmacy – it’s legal. In both layout and content, the adver-

tisement was a response to an article run the previous month by the same magazine entitled: Get stoned at the pharmacy – it’s

legal. The School’s advertisement was edited slightly to become the flyer for the School’s annual Open House Day. The flyer was

also handed out to upper secondary schools in the autumn of 2001 at study orientation meetings called STORM meetings.

Advertising

Publications

DEPARTMENT OF ANALYTICAL

AND PHARMACEUTICAL CHEMISTRY

Andersen HR, Wollenberger L, Halling-Sørensen B, Kusk KO.Development of copopod nauplii to copepodites - A parameter forchronic toxicity including endocrine disruption. Environ Tox and Chem2001;20:2821-2829.

Bendahl L, Gammelgaard B, Jøns O, Farver O, Hansen SH.Interfacing capillary electrophoresis with inductively coupled plasmamass spectrometry by direct injection nebulization for selenium specia-tion. J Anal At Spectrom. 2001;16:38-42.

Bendahl L, Hansen SH, Gammelgaard B. Capillaries modified bynon-covalent anionic polymer adsorption for capillary zone elec-trophoresis, micellar electrokinetic capillary chromatography and capil-lary electrophoresis mass spectrometry. Electrophoresis2001;22:2565-73.

Corcoran O, Mortensen RW, Hansen SH, Troke J, Nicholson JK.HPLC/1H NMR spectroscopic studies of the reactive -1-O-acyl isomerformed during acyl migration of S-naproxen-1-O-acyl glucuronide.Chem Res Toxicol 2001;14:1363-1370.

Daykin CA, Corcoran O, Hansen SH, Bjørnsdottir I, Cornett C,Connor SC, Lindon JC, Nicholson JK. Application of directly-cou-pled HPLC-NMR to separation and characterisation of lipoproteinsfrom human serum. Anal Chem 2001;73:1084-1090.

Farver O, Zhang J, Chi O, Pecht I, Ulstrup J. Deuterium IsotopeEffect on the Intramolecular Electron Transfer in Pseudomonas aerugi-nosa Azurin, Proc Natl Acad Sci 2001;98:4426-4430.

Farver O, Kroneck PMH, Zumft WG, Pecht I. Intra-protein electrontransfer processes - from model proteins to enzymatic reaction cycles.J Inorg Biochem 2001;86:84-86.

Gabel-Jensen C, Hansen SH, Pedersen-Bjergaard S. Separation ofneutral compounds by microemulsion electrokinetic chromatography.Fundamental studies on selectivity. Electrophoresis 2001;22:1330-1336.

Gammelgaard B, Bendahl L, Jøns O. Selenium speciation in humanurine. Plasma Source Mass Spectrometry: The New Millenium2001;401-411.

Gammelgaard B, Jøns O, Bendahl L. Selenium speciation in pre-treated human urine by ion-exchange chromatography and ICP-MSdetection. J Anal At Spectrom 2001;16:339-344.

Guardo AD, Calamari D, Benfenati E, Halling-Sørensen B, ZucattoE, Fanelli R. Pharmaceuticals as Environmental Contaminats:

Modelling Distribution of fate. Pharmaceuticals in the environment -Sources, fate, effects and risks 2001;91-102.

Halling-Sørensen B, Holten Lützhøft HC, Andersen HR, Ingerslev F.Environmental Risk Assessment of Antibiotics; Comparison ofMecillinam, Trimethoprim and Ciprofloxacin. J AntimicrobialChemotherapy 2000;46:53-58.

Halling-Sørensen B. Inhibition of aerobic growth and nitrification ofbacteria in sewage sludge by antibacterial agents Arch EnvironContam Toxicol 2001;40:451-460.

Halling-Sørensen B, Jensen J, Tjørnelund J, Montfors MHMM.Worst-case estimations of predicted environmental soil concentrations(PEC) of selected veterinary antibiotics and residues in DanishAgriculture. Pharmaceuticals in the environment - Sources, fate,effects and risks 2001;143-156.

Halling-Sørensen B, Sengeløv G, Tjørnelund J. Toxicity ofTetracyclines and Tetracycline degradation products to environmentalrelevant bacteria including selected Tetracycline resistant bacteria.Arch Environ Contam Toxicol (in press).

Hansen HH, Hansen SH, Schousboe A, Hansen HS. Determinationof an anandamide precursor (N-acylethanolamine phospholipid) andother N-acylethanolamine phospholipids following sodium azide-in-duced neurotoxicity in cortical neurons. J Neurochem 2000;75:861-871.

Hansen HH, Ikonomidou C, Bittigau P, Hansen SH, Hansen HS.Accumulation of the anandamide precursor and other N-acylethanolamine phospholipids in infant rat models of in vivo necroticand apoptotic neuronal death. J Neurochem 2001;76:39-46.

Hansen SH, Bjørnsdottir I, Tjørnelund J. Nonaqueous CapillaryElectrophoresis. Encyclopedia of Separation Science 2000;1293-1300.

Hansen SH, Gabel-Jensen C, Pedersen-Bjergaard. Comparison ofmicroemulsion electrokinetic chromatography and solvent modified mi-cellar electrokinetic chromatography. J Sep Sci 2001;24:643-650.

Hansen SH, Gabel-Jensen C, El-Sherbiny DTM, Pedersen-Bjergaard S. Microemulsion electrokinetic chromatography - orsolvent-modified micellar electrokinetic chromatography? TRAC2001;20:614-619.

Jensen AG, Hansen SH, Nielsen EØ. Adhyperforin as a contributorto the effect of Hypericum perforatum L. in biochemical models of an-tipressant activity. Life Sciences 2001;68:1593-1605.

Jensen AG, Cornett C, Gudiksen L, Hansen SH. Characterization ofextracts of Hypericum perforatum L. Using an on-line HPLC system withUV/VIS and fluorescence detection before as well as after photochemi-cal conversion of the effluent. Phytochemical Analysis 2000;11:387-394.


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Jensen CG, Hansen SH, Pedersen-Bjergaard S. Separation of neutralcompounds by microemulsion electrokinetic chromatography.Fundamental studies on selectivity. Electrophoresis 2001;22:1330-1336.

Jørgensen SE. Application of exergy and specific exergy as ecologicalindicators of coastal areas. Aquatic Ecosystem Health andManagement 2000;3:419-430.

Jørgensen SE, Trepel M, Davidson T. Quantitative simulation of bio-chemical processes in petlands as a tool to define sustainable use?Suo 2000;3:83-93.

Jørgensen SE. Toward a Consistent Pattern of Ecosystem Theories.The Scientific World 2001;1:71-75.

Jørgensen SE. The thermodynamic Concept Exergy.Thermodynamics and Ecological Modelling 2001;153-164.

Jørgensen SE. A tentative Fourth Law of Thermodynamics.Thermodynamics and Ecological Modelling 2001;302-348.

Jørgensen SE, Marques JC. Thermodynamics and ecosystem theo-ry, case studies from hydrobiology. Hydrobiologia 2001;445:1-10.

Jørgensen SE. Exergy of an isolated living system may increase.Advances in Energy Studies 2001;573-580.

Jørgensen SE. Parameter estimation and calibration by use of exergy.Ecological Modelling 2001;146:299-302.

Jørgensen SE. Recent Developments in System Ecology. IntegrativeSystem Approaches to Natural and Social Dynamics 2001;155-170.

Larsen SW, Thomsen AE, Rinvar E, Friis GJ, Larsen C. Effect ofdrug lipophilicity on in vitro release rate from oil vehicles using nicotinicacid esters as model prodrug derivatives. Int J Pharm 2001;216:83-93.

Larsen DB, Fredholt K, Larsen C. Addition of hydrogen bond donat-ing excipients to oil solution: effect on in vitro release rate and viscosi-ty. Eur J Pharm Sci 2001;13:403-410.

Larsen SW, Rinvar E, Svendsen O, Lykkesfeldt J, Friis GJ, LarsenC. Determination of the disappearance rate of iodine-125 labelled oilsfrom the injection site after intramuscular and subcutaneous adminis-tration to pigs. Int J Pharm 2001;230,67-75.

Loke ML, Tjørnelund J, Halling-Sørensen B. Determination of thedistribution coefficient (log kd) of oxytetracycline, tylosin, olaquindoxand metronidazole in manure. Chemosphere (accepted).

Mortensen RW, Corcoran O, Cornett C, Sidelmann UG, Throke J,Lindon JC, Nicholson JK, Hansen SH. LC-1H NMR used for deter-mination of the elution order of S-naproxen glucuronide isomers in twoisocratic reversed-phase LC-systems. J Pharm Biomed Anal2001;24:477-485.

Mortensen RW, Corcoran O, Cornett C, Sidelmann UG, Lindon JC,Nicholson JK, Hansen SH. S-naproxen-1-O-acyl glucuronide degra-dation kinetic studies by stopped-flow HPLC-1H NMR and HPLC-UV.Drug Metabolism and Disposition 2001;29:375-380.

Ray S, Berec L, Straskraba M, Jørgensen SE. Optimization of exer-gy and implication of body sizes of phytoplankton and zooplankton inan aquatic ecosystem model. Ecological Modelling volume2001;140:219-234.

Pedersen-Bjergaard S, Jensen CG, Hansen SH. Selectivity in mi-croemulsion electrokinetic chromatography. J Chromatogr A2000;897:375-381.

Strømgaard K, Bjørnsdottir I, Andersen K, Brierley MJ, Rizoli S,Eldursi N, Mellor IR, Usherwood PNR, Hansen SH, Krogsgaard-Larsen P, Jaroszewski J. Solid phase synthesis and biological evalu-ation of enantiomerically pure wasp toxin analogues PhTX-343 andPhTX-12. Chirality 2000;12:93-102.

Wang J, Hansen EH, Gammelgaard B. Flow injection on-line dilutionfor multi-element determination in human urine with detection by in-ductively coupled plasma mass spectrometry. Talanta 2001;55:117-126.

PHD THESES

Gyldenkærne S. Risk Assessment of Pesticides in Agricultural Fieldswith Special Emphasis on Carabids and Staphylinids. The RoyalDanish School of Pharmacy, 2000.

Jensen AG. Quality Assessment of Herbal Remedies. Focus onPhytopharmaceuticals Containing Hypericum perforatum L. and Ginkobiloba L. Department of Analytical and Pharmaceutical Chemistry, TheRoyal Danish School of Pharmacy, 2001.

Jensen MS. Cyanide Toxicology – Insights into Mechanisms of Actionand Antidotal Strategies. Department of Analytical and PharmaceuticalChemistry, The Royal Danish School of Pharmacy, 2000.

Larsen DB. Parenteral depot formulations - pharmaceutical chemicalcharacterization of oil solutions. Royal Danish School of Pharmacy,Dept. of Analytical and Pharmaceutical Chemistry, 2001.

Lützhøft H-CH. Environmental Risk Assessment of Antimicrobials.Royal Danish School of Pharmacy, Department of Analytical andPharmaceutical Chemistry, 2000.

Kayombo S. Development of a Holistic Model for the design ofFacultative Waste Stabilisation Ponds in Tropical Climate. Section ofEnvironmental Chemistry, Department of Analytical and PharmaceuticalChemistry, Royal Danish School of Pharmacy, 2001.

Mortensen RW. Reactive Drug Metabolites: Investigations of R- andS-naproxen-1-0-acyl glucuronide degradation using enzymes, HPLCand NMR. Department of Analytical and Pharmaceutical Chemistry,Royal Danish School of Pharmacy, 2000.

Sidenius U. Purification and analysis of selenoprotein P from humanplasma. The Royal Danish School of Pharmacy, Dept. of Analytical andPharmaceutical Chemistry, 2000.

OTHER PUBLICATIONS

Bendahl L, Gammelgaard B, Jøns O, Farver O, Hansen SH.Højfølsomme mikroteknikker til analyse af blod og urin. [Sensitive mi-cro techniques for analysis of blood and urine] Lægemiddelforskning2001;36-37.

Halling-Sørensen B. Miljøforurening fra rester af antibiotika i organiskaffald og husdyrgødning. [Environmental pollution from residue of an-tibiotic in organic waste and domestic animal manure] Miljøforskning2001;49.

Hansen HH, Hansen SH, Hansen HS. Hjernens cannabis-lignendestoffer modvirker hjernedød. [The cannabis like drugs of the brain pre-vent brain death] Lægemiddelforskning 2000;26-27.

Hansen SH. Naturlægemidler og mineralpræparater. Sammenhængmellem indhold og virkning? [Natural medicine and mineral prepara-tions. A connection between content and effect?] Farmaci2000;107:22-26.

Hansen SH, Jensen AG, Cornett C. PERIKON – Den „grønne“lykkepille. [PERIKON – the ”green” prozac] Farmaci 2001;108:26-27.

Jensen AG, Cornett C, Hansen SH. Naturlægemidler.[Naturalmedicine] Dansk Kemi 2001;82:16-20.

Jørgensen SE. Milan Straskraba, editorial Ecological Modelling2001;140:193-194.

PUBLICATIONS

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Jørgensen SE. Foreword to the book “Pharmaceuticals in the environ-ment. Sources, Fate, Effects and Risks” edited by Kalus Kümmerer2001.

Jørgensen SE, Bendoricchio G. Fundamentals of EcologicalModelling 3. Edition. 2001.

Olsen J, Bjørnsdottir I, Tjørnelund J, Hansen SH. På sporet afbivirkningen. [Tracking down the side effect] Lægemiddelforskning2000;10-11.


Andersen L, Clausen V, Oketch-Rabah HA, Lechtenberg M,Adsersen A, Nahrstedt A, Jaroszewski JW. Gynocardin andcyclopentenylglycine in Rawsonia lucida. Biochem Syst Ecol29;2001:219-222.

Andersen L, Nielsen B, Jaroszewski JW. Synthesis of epimers of L-cyclopentenylglycine using enzymatic resolution. Chirality12;2000:665-669.

Bang-Andersen B, Ahmadian H, Lenz SM, Stensbøl TB, MadsenU, Bøgesø KP, Krogsgaard-Larsen P. Structural determinants ofAMPA agonist activity in anlogues of 2-amino-3-(3-carboxy-5-methyl-4-isoxazolyl)propionic acid: Synthesis and pharmacology. J Med Chem43;2000:4910-4918.

Banke TG, Greenwood JR, Christensen JK, Liljefors T, TraynelisSF, Schousboe A, Pickering DS. Identification of amino acid residuesin GluR1 responsible for ligand binding and desensitization. J Neurosci21;2001:3052-3062.

Begtrup M. Small-scale filtration using a modified plastic syringe. JChem Ed 78;2001:543.

Boström J, Gundertofte K, Liljefors T. A pharmacophore model fordopamine D4 receptor antagonists. J Comput-Aided Mol Des14;2000:769-786.

Bräuner-Osborne H, Jensen AA, Sheppard PO, Brodin B,Krogsgaard-Larsen P, O’Hara P. Cloning and characterization of ahuman orphan family C G-protein coupled receptor GPRC5D. BiochimBiophys Acta 1518;2001:237-248.

Bräuner-Osborne H, Nielsen MB, Nielsen B, Krogsgaard-Larsen P,Johansen TN. A new structural class of subtype-selective inhibitor ofcloned excitatory amino acid transporter, EAAT2. Eur J Pharmacol406;2000:41-44.

Breu J, Domel H, Norrby P-O. Chiral recognition among trisdiimine –metal complexes, 7. Racemic compound formation versus conglomer-ate formation with [M(bpy)3](PF6)2 (M = Ni, Zn, Ru): Lattice energy min-imisations and implications for structure prediction. Eur J Inorg Chem2000:2409-2419.

Bunch L, Johansen TH, Bräuner-Osborne H, Stensbøl TB,Johansen TN, Krogsgaard-Larsen P, Madsen U. Synthesis and re-ceptor binding affinity of new selective GluR5 ligands. Bioorg MedChem 9;2001:875-879.

Bunch L, Norrby P-O, Frydenvang K, Krogsgaard-Larsen P,Madsen U. Unprecedented migration of N-alkoxycarbonyl groups inprotected pyroglutaminol. Org Lett 3;2001:433-435.

Campiani G, Morelli E, Nacci V, Fattorusso C, Ramunno A,Novellino E, Greenwood J, Liljefors T, Griffiths R, Sinclair C,Reavy H, Kristensen AS, Pickering DS, Schousboe A, Cagnotto A,Fumagalli E, Mennini T. Characterization of the 1H-cyclopentapyrimi-dine-2,4(1H,3H)-dione derivative (S)-CPW399 as a novel, potent, andsubtype-selective AMPA receptor full agonist with partial desensitiza-tion properties. J Med Chem 44;2001:4501-4504.

Chen M, Zhai L, Christensen SB, Theander TG, Kharazmi A.Inhibition of Furamate reductase in Leishmania major and L. donovaniby chalcones. Antimicrob Agents Chemother 45;2001:2023-2029.

Christensen J, Jaroszewski JW. Natural glycosides containing al-lopyranose from the passion fruit plant and circular dichroism of ben-zaldehyde cyanohydrin glycosides. Org Lett 3;2001:2193-2195.

Christensen SB, Kharazmi A. Antimalarial Natural Products (chapter9). In: Bioactive Compounds from Natural Sources, editor Tringali C.London: Taylor and Francis, 2001.

Clausen V, Wellendorph P, Ekpe P, Jaroszewski JW. Tetraphyllin B,volkenin and cyclopentenyl-glycine in Androsiphonia adenostegia.Biochem Syst Ecol 29;2001:317-319.

Ebert B, Mortensen M, Thompson SA, Kehler J, Wafford KA,Krogsgaard-Larsen P. Bioisosteric determinants for subtype selectivi-ty of ligands for heteromeric GABAA receptors. Bioorg Med Chem Lett11;2001:1573-1577.

Eldrup AB, Nielsen BB, Haaima G, Rasmussen H, Kastrup JS,Christensen C, Nielsen PE. 1,8-Naphthyridin-2(1H)-ones. Novel bi-and tricyclic analogues of thymine in peptide nucleic acids (PNAs). EurJ Org Chem 2001;1781-1790.

Eriksen BL, Vedsø P, Begtrup M. Synthesis of 4- and 5- substituted1-hydroxyimidazoles through directed lithiation and metal-halogen ex-change. J Org Chem 66;2001:8344-8348.

Eskildsen J, Vedsø P, Begtrup M. Synthesis of 2-alkylpyrazole-1-ox-ides: A facile access to 1-alkyl-5-halopyrazoles. Synthesis 72001;1053-1056.

Friedrichsen GM, Jakobsen P, Taub M, Begtrup M. Application ofenzymatically stable dipeptides for enhancement of intestinal perme-ability. Synthesis and in vitro evaluation of dipeptid-coupled com-pounds. Bioorg Med Chem 9;2001:2625-2632.

Friedrichsen GM, Nielsen CU, Steffansen B, Begtrup M. Modelprodrugs designed for the intestinal peptide transporter. A syntheticapproach for coupling of hydroxy-containing compounds to dipep-tides. Eur J Pharm Sci 14;2001:13-19.

Frølund B, Tagmose L, Liljefors T, Stensbøl TB, Engblom C,Kristiansen U, Krogsgaard-Larsen P. A novel class of potent 3-isoxazolol GABAA antagonists: Design, synthesis and pharmacology. J Med Chem 43;2000:4930-4933.

Garibay P, Vedsø P, Begtrup M, Hoeg-Jensen T. Solid-phase direct-ed ortho-lithiation and the preparation of a phthalide library. J CombChem 3;2001:332-340.

Havez S, Begtrup M, Vedsø P, Andersen K, Ruhland T.Palladium(0)-catalyzed arylation of resin-bound imidazol-2-ylzinc chlo-rides. Synthesis 2001:909-913.

Høgedal BD, Mølgaard P. HPLC analysis of the seasonal and diurnalvariation of iridoids in cultivars of Antirrhinum majus. Biochem SystEcol 28;2000:949-962.

Jakobsen CM, Denmeade SR, Isaacs JT, Gady A, Olsen CE,Christensen, SB. Design, synthesis, and pharmacological evaluationof thapsigargin analogues for targeting apostosis to prostatic cancercells. J Med Chem 44;2001:4696-4703.

Jakobsen TH, Marcussen HV, Adsersen A, Strasberg D, Smitt UW,Jaroszewski JW. 3-Methoxyflavones and a novel coumarin fromPsiadia dentata. Biochem Syst Ecol 29;2001:963-965.

Jensen J, Skjærbæk N, Vedsø P. Preparation of 2- and 5-aryl substi-tuted thiazoles via Palladium-catalyzed Negishi cross-coupling.Synthesis 2001;128-134.


PAGE 110

Jensen AA, Madsen BE, Krogsgaard-Larsen P, Bräuner-Osborne H.Pharmacological characterization of homobaclofen on wild type andmutant GABAB1b receptors coexpressed with the GABAB2 receptor.Eur J Pharmacol 417;2001:177-180.

Jensen AA, Sheppard PO, O'Hara PJ, Krogsgaard-Larsen P,Bräuner-Osborne H. The role of Arg78 in the metabotropic glutamatereceptor mGlu1 for agonist and selectivity. Eur J Pharmacol2000;397:247-253

Jensen AA, Sheppard PO, Jensen LB, O’Hara PJ, Bräuner-Osborne H. Construction of a high affinity zinc binding site in themetabotropic glutamate receptor mGluR1. J Biol Chem276;2001:10110-10118.

Jensen AA, Spalding TA, Burstein ES, Sheppard PO, O’Hara PJ,Brann MR, Krogsgaard-Larsen P, Bräuner-Osborne H. Functionalimportance of the Ala116-Pro136 region in the calcium-sensing receptor.J Biol Chem 275;2000:29547-29555.

Jensen KP, Sauer SPA, Liljefors T, Norrby P-O. Theoretical investi-gation of steric and electronic effects in coenzyme B12 models.Organometallics 20;2001:550-556.

Johansen TN, Stensbøl TB, Nielsen B, Vogensen SB, FrydenvangK, Sløk FA, Bräuner-Osborne H, Madsen U, Krogsgaard-Larsen P.Resolution, configurational assignment, and enantiopharmacology atglutamate receptors of 2-amino-3-(3-carboxy-5-methyl-4-isoxazolyl)propionic acid (ACPA) and demethyl-ACPA. Chirality13;2001:523-532.

Kastrup JS, Linde V, Pedersen AK, Stoffer B, Iversen LF, LarsenIK, Rasmussen PB, Flodgaard HJ, Bjørn SE. Two mutants of humanheparin binding protein (CAP37): Toward an understanding of the na-ture of lipid A/LPS and BPTI binding. Proteins: Struct Funct Genet42;2001:442-451.

Krebs FC, Jørgensen M, Lebech B, Frydenvang K. A perdeuteratedcryoprotectant for neutron studies and a demonstration of its use forneutron powder diffraction on L-(—)-ephedrine hemihydrate. J ApplCryst 34;2001:203-207.

Kreilgaard M, Pedersen EJ, Jaroszewski JW. NMR characterisationand transdermal drug delivery potential of microemulsion systems. JControlled Release 69;2000:421-433.

Kristensen J, Lysén M, Vedsø P, Begtrup M. Synthesis of ortho sub-stituted arylboronic esters by in situ trapping of unstable lithio interme-diates. Org Lett 3;2001:1435-1437.

Krogsgaard-Larsen P, Frølund B, Frydenvang K. GABA uptake in-hibitors. Design, molecular pharmacology and therapeutic aspects.Curr Pharm Des 6;2000:1193-1209.

Kromann H, Sløk FA, Johansen TN, Krogsgaard-Larsen P. A con-venient synthesis of 4-substituted 3-ethoxy-5-methylisoxazoles by pal-ladium-catalyzed coupling reactions. Tetrahedron 57;2001:2195-2201.

Larsen ST, Hansen JS, Thygesen P, Begtrup M, Poulsen OM,Nielsen GD. Adjuvant and immuno-suppressive effect of six monoph-thalates in a subcutaneous injection model with BALB/c mice.Toxicology 169;2001:37-51.

Larsen TO, Frydenvang K, Frisvad JC. UV-guided screening of ben-zodiazepine producing species in Penicillium. Biochem Syst Ecol28;2000:881-886.

Mader MM, Norrby P-O. Quantum chemical investigation of mecha-nism of silane oxidation. J Am Chem Soc 123;2001:1970-1976.

Madsen U, Bräuner-Osborne H, Frydenvang K, Hvene L,Johansen TN, Nielsen B, Sánchez C, Stensbøl TB, Bischoff F,Krogsgaard-Larsen P. Synthesis and pharmacology of 3-isoxazololamino acids as selective antagonists at group I metabotropic glutamicacid receptors. J Med Chem 44;2001:1051-1059.

Madsen U, Johansen TN, Stensbøl TB, Krogsgaard-Larsen P.Pharmacology of AMPA/kainate receptors. In: Glutamate and GABAreceptors and transporters. Eds: Egebjerg J, Schousboe A,Krogsgaard-Larsen P. London: Taylor and Francis Books Ltd 2001;pp. 99-118.

Madsen U, Stensbøl TB, Krogsgaard-Larsen P. Inhibitors of AMPAand kainate receptors. Curr Med Chem 8;2001:1291-1301.

Mølgaard P, Chihaka A, Lemmich E, Furu P, Windberg C, IngerslevF, Halling-Sørensen B. Biodegradability of the Molluscicidal Saponinsof Phytolacca dodecandra. Regul Toxicol Pharmacol 32;2000:248-255.

Mølgaard P, Ndamba J, Lemmich E, Chihaka A, Furu P. PhytolaccaDodecandra used as a molluscicide in Zimbabwe. In: Timberlake J &Kativu S (Eds), African Plants: Biodiversity, Taxonomy and Uses.Ethnobotany and Uses of African Plants Symposium Poster Abstracts.Royal Botanic Gardens, Kew, 1999:507.

Mølgaard P, Nielsen SB, Rasmussen DE, Drummond RB, MakazaN, Adreassen J. Anthelmintic screening of Zimbabwean plants tradi-tionally used against schistosomiasis. J Ethnopharmacol 2001;74:257-264

Nielsen PA, Jaroszewski JW, Norrby P-O, Liljefors T. An NMR andab initio quantum chemical study of acid-base equilibria for conforma-tionally constrained acidic �-amino acids in aqueous solution. J AmChem Soc 123;2001:2003-2006.

Nielsen PA, Liljefors T. Conformational analysis of kainate in aqueoussolution in relation to its binding to AMPA and kainic acid receptors. JComput-Aided Mol Des 15;2001:753-763.

Norrby P-O, Brandt P. Deriving force field parameters for coordinationcomplexes. Coord Chem Rev 212;2001:79109.

Olafsdottir ES, Omarsdottir S, Jaroszewski JW. Constituents ofthree Icelandic Alchemilla species. Biochem Syst Ecol 29;2001:959-962.

Pawlas J, Greenwood J, Vedsø P, Liljefors T, Jakobsen P,Huusfeldt PO, Begtrup M. Halogenation of pyrazoloquinolines andpyrazoloisoquinolines. Thereoretical analysis of the regioreactivity andcross-coupling of 3-halogen derivatives. J Chem Soc Perkin Trans I2001:861-866.

Pawlas J, Vedsø P, Jakobsen P, Huusfeldt PO, Begtrup M.Synthesis of 1-hydroxy-substituted pyrazolo[3,4-c]- and pyrazolo[4,3-c]quinolines and isoquinolines from 4- and 5-aryl-substituted 1-benzy-loxypyrazoles. J Org Chem 65;2000:9001-9006.

Rasmussen HB, Christensen SB, Kvist LP, Kharazmi A, HuansiAG. Absolute configuration and antiprotozoal activity of minquartynoicacid. J Nat Prod 63;2000:1295-1296.

Rasmussen T, Norrby P-O. Characterization of new six-memberedtransition states of the amino-alcohol promoted addition of dialkyl zincto aldehydes. J Am Chem Soc 123;2001:2464-2465.

Rist Ø, Begtrup M. Synthesis of a new analogue of BINOL based ona homodimer of substituted 1-hydroxypyrazole. J Chem Soc PerkinTrans I 2000:1566-1568.

Rønsted N, Göbel E, Franzyk H, Jensen SR, Olsen CE.Chemotaxonomy of Plantago. Iridoid glucosides and caffeoylphenylethanoid glycosides. Phytochemistry 55;2000:337-348.

Sairafianpour M, Christensen J, Stærk D, Budnik BA, Kharazmi A,Bagherzadeh K, Jaroszewski JW. Leishmanicidal, antiplasmodial,and cytotoxic activity of novel diterpenoid 1,2-quinones from Perovskiaabrotanoides: New source of tanshinones. J Nat Prod 64;2001:1398-1403.

PUBLICATIONS

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Sandager L, Stymne S. Characterization of enzymes determining fat-ty acid chain lenght in developing seeds of Limnanthes douglasii. JPlant Phys 156;2000:617-622.

Simonsen HT, Nordskjold JB, Smitt UW, Nyman U, PushpangadanP, Joshi P, Varughese G. In vitro screening of Indian medicinal plantsfor antiplasmodial activy. J Ethnopharmacol 74;2001,195-204.

Sløk FA, Bräuner-Osborne H, Stensbøl TB, Johansen TN, Ebert B,Mortensen M, Nielsen B, Madsen U, Brehm L, Falch E,Krogsgaard-Larsen P. Structural and stereochemical requirements foractivation and blockade of excitatory amino acid receptors.

Smith L, Andersen KB, Hovgaard L, Jaroszewski JW. Rational se-lection of antisense oligonucleotide sequences. Eur J Pharm Sci11;2000:191-198.

Stensbøl TB, Jensen HS, Nielsen B, Johansen TN, Egebjerg J,Frydenvang K, Krogsgaard-Larsen P. Stereochemistry and molecularpharmacology of (S)-thio-ATPA, a new potent and selective GluR5 ag-onist. Eur J Pharmacol 411;2001:245-253.

Strømgaard K, Andersen K, Krogsgaard-Larsen P, JaroszewskiJW. Recent advances in the medicinal chemistry of polyamine toxins.Mini Rev Med Chem 1;2001:317-338.

Strømgaard K, Andersen K, Ruhland T, Krogsgaard-Larsen P,Jaroszewski JW. A versatile method for solid-phase synthesis ofpolyamines: Neuroactive polyamine toxins as example. Synthesis 62001:877-884.

Strømgaard K, Brier TJ, Andersen K, Mellor IR, Saghyan A,Tikhonov D, Usherwood PNR, Krogsgaard-Larsen P, JaroszewskiJW. Solid-phase synthesis and biological evaluation of a combinatoriallibrary of philanthotoxin analogues. J Med Chem 43;2000:4526-4533.

Stærk D, Christensen J, Lemmich E, Duus JØ, Olsen CE,Jaroszewski JW. Cytotoxic activity of some phenanthroindolizidine N-oxide alkaloids from Cynanchum vincetoxicum. J Nat Prod63;2000:1584-1586.

Stærk D, Norrby P-O, Jaroszewski JW. Conformational analysis ofindole alkaloids corynantheine and dihydrocorynantheine by dynamic1H NMR spectroscopy and computational methods: Steric effects ofethyl vs vinyl group. J Org Chem 66;2001:2217-2221.

Sørensen US, Falch E, Stensbøl TB, Jaroszewski JW, Madsen U,Krogsgaard-Larsen P. Structural determinants for AMPA agonist ac-tivity of aryl or heteroaryl subtstituted AMPA analogues. Synthesis andpharmacology. Arch Pharm Pharm Med Chem 334;2001:62-68.

Sørensen US, Krogsgaard-Larsen P. Synthesis and synthetic utilityof 3-isoxazolols. Org Prep Proced Int 33;2001:515-564.

Terp GE, Johansen BN, Christensen IT, Jørgensen FS. A new con-cept for multidimensional selection of ligand conformations(Multiselect) and multidimensional scoring (Multiscore) of protein –ligang binding affinities. J Med Chem 44;2001:2333-2343.

Tønder JE, Olesen PH, Hansen JB, Begtrup M, Pettersson I. Animproved nicotinic pharmacophore and a stereoselective CoMFA-mod-el for nicotinic agonists acting at the central nicotinic acetylcholine re-ceptors labelled by [3H]-N-methylcarbamylcholine. J Comput-AidedMol Des 15;2001:247-258.

Vogensen SB, Jensen HS, Stensbøl TB, Frydenvang K, Bang-Andersen B, Johansen TN, Egebjerg J, Krogsgaard-Larsen P.Resolution, configurational assignment, and enantiopharmacology of2-amino-3-[3-hydroxy-5-(2-methyl-2H-tetrazol-5-yl)isoxazol-4-yl]propi-onic acid, a potent GluR3- and GluR4-preferring AMPA receptor ago-nist. Chirality 12;2000:705-713.

Wellendorp P, Clausen V, Jørgensen LB, Jaroszewski JW.Cyclopentanoids of Mathurina penduliflora. Biochem Syst Ecol29;2001:649-651.

PHD THESES

Buchardt J. A solid phase combinatorial approach to phosphinic pep-tide inhibitors of matrix metalloproteinases. Carlsberg Laboratory andRoyal Danish School of Pharmacy, 2000.

Friedrichsen GM. Peptide-coupled compounds targeted for theoligopeptide transporter: Synthesis and biological evaluation. RoyalDanish School of Pharmacy, 2001.

Garibay P. The combinatorial synthesis of possible insulin mimetics.Royal Danish School of Pharmacy, 2000.

Jakobsen CM. Design, synthesis, and pharmacological evaluation ofThapsigargin analogues and prodrugs for targeting apoptosis to pro-static cancer cells. Royal Danish School of Pharmacy, 2001.

Jensen AA. Molecular pharmacology of family C G G-protein coupledreceptors. Royal Danish School of Pharmacy, 2001.

Kromann H. Glutamate receptor-ligands: Synthesis and pharmacolog-ical characterization. Royal Danish School of Pharmacy, 2000.

Nielsen PA. Strongly polar molecules in aqueous solution studied byNMR and computational chemistry. Royal Danish School of Pharmacy,2000.

Pawlas JI. Construction and functionalization of annelated 1-hydrox-ypyrazoles. II Nickel-catalyzed hydroamination of 1,3-dienes using alkylamines. Royal Danish School of Pharmacy, 2001.

Rasmussen T. Molecular modeling of asymmetric catalysts. RoyalDanish School of Pharmacy, 2001.

Sams AG. Solid phase aldol and Diels-Alder reactions in the formationof novel peptide isosters as putative protease inhibitors. Royal DanishSchool of Pharmacy, 2000.

Sandager L. Genes and enzymes involved in the biosynthesis of tria-cylglycerol in plants and yeast. Swedish University of AgriculturalSciences, Alnarp and Royal Danish School of Pharmacy, 2001.

Terp GE. Molecular modeling of matrix metalloproteinases and their in-hibitors: A new concept for ligand selection and prediction of bindingaffinities. Royal Danish School of Pharmacy, 2001.

Willert M. A combinatorial library approach to the identification of pro-tease substrates and inhibitors. Carlsberg Laboratory and RoyalDanish School of Pharmacy, 2001.

OTHER PUBLICATIONS

Christensen J, Stærk D, Ziegler HL, Sairafianpour M, Jaroszewski,JW. Forbedret test af nye lægemidler mod malaria [Improved assay fornew antimalarial drugs]. Lægemiddelforskning 2001;8-9.

Clausen RP, Greenwood J, Larsson OM, Krogsgaard-Larsen P. Etbud på fremtidens lægemidler mod epilepsi [Future anti-epilepticdrugs]. Lægemiddelforskning 2001;20-21.

Frølund B, Kristiansen U, Stensbøl TB, Krogsgaard-Larsen P. Nynøgle til behandling af skizofreni? [A new strategy for treatment ofschizophrenia?]. Lægemiddelforskning 2000;24-25.

Hogner A, Lunn M-L, Kastrup JS, Larsen IK, Liljefors T, EgebjergJ. Design af lægemidler mod neurodegenerative sygdomme [Structurebased design of drugs against neurodegenerative diseases].Lægemiddelforskning 2000;32-33.

Høst J, Jørgensen FS, Christensen IT, Hovgaard L, Frøkjær S.Computeren er medicinalindustriens krystalkugle.Lægemiddelforskning 2001;28-29.


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Jensen AA, Bräuner-Osborne H. Øget forståelse af vigtig receptor ihjernen [Increased understanding of important receptor in the brain].Lægemiddelforskning 2000;28-29.

Jørgensen FS, Kristensen JB, Christensen IT. E-screening aflægemidler [e-Screening of Drugs]. Lægemiddelforskning 2001;30-31.

Krogsgaard-Larsen P, Brehm L. Fra svampegift til potentieltlægemiddel med ny virkning [From mushroom toxin to potential drugwith new clinical profile]. Lægemiddelforskning 2001;2-5.

Madsen U, Stensbøl TB, Bräuner-Osborne H, Sánchez C. Frakrampefremkaldende til krampestillede effekt [From convulsive to anti-convulsive activity]. Lægemiddelforskning 2001;18-19.

Mortensen M, Kehler J, Krogsgaard-Larsen P, Ebert, B. Nytlægemiddel forbedrer søvnen [New drug improves sleep pattern].Lægemiddelforskning 2001;6-7.

Mølgaard P, Cornett C. Rationel omgang med naturlægemidler [A ra-tional approach to herbal medicine]. Dansk Kemi 2001;82.

Mølgaard P, Johnsen S, Christensen P, Cornett C. Kemisk og biolo-gisk evaluering af ekstrakter og stoffer fra Rød Solhat [Chemical andbiological evaluation of extracts and compounds from Echinacea pur-purea]. Dansk Kemi 2001;82:10-13.

Stærk D, Lemmich E, Franzyk H, Lemmich J, Christensen SB,Jaroszewski JW. Moderne naturstofkemi: Effektiv analyse af naturensstofbiblioteker [Modern natural products chemistry: Efficient analysis ofnatural compound libraries]. Lægemiddelforskning 2000;6-7.

Vogensen SB, Stensbøl TB, Egebjerg J, Frydenvang K, JohansenTN, Krogsgaard-Larsen P. Design af lægemidler mod Alzheimerssygdom [Design of drugs for the treatment of Alzheimers disease].Lægemiddelforskning 2000;30-31.

Wenckens M, Vedsø P, Begtrup M, Jakobsen P. Håb om bedre be-handling af brystkræft [Search for improved pharmaceuticals for treat-ment of mammary cancer]. Lægemiddelforskning 2001;14-15.


Bagger MA, Nielsen HW, Bechgaard E. Nasal bioavailability of pep-tide T in rabbits: absorption enhancement by sodium glycocholate andglycofurol. Eur J Pharm Sci 2001;14:69-74.

Bjerregaard S, Wulf–Andersen, Stephens RW, Lund RL,Vermehren C, Söderberg I, Frokjaer S. Sustained elevated plasmaaprotinin concentration in mice following intraperitoneal injections ofw/o emulsions incorporating aprotinin, J Contr Release 2001;71:87-98.

Bjerregaard S, Söderberg I, Vermehren C, Frokjaer S. Acceleratedstability testing of a water-in-oil emulsion, J Disper Sci Tech 2001;22:23-31.

Bjerregaard S, Pedersen H, Vedstesen H, Vermehren C,Söderberg I, Frokjaer S. Parenteral water/oil emulsions containinghydrophilic compounds with enhanced in vivo retention: formulation,rheological characterisation and study of the in vivo fate using wholebody gamma-scintigraphy, Int. J Pharm 2001;215:13-27.

Bjerregaard S, Vermehren C, Soderberg I, Frokjaer S. Acceleratedstability testing of a water-in-oil emulsion. J Disper Sci Tech2001;22:23-31.

Bønløkke L, Hovgaard L, Kristensen HG, Knutson L, Lennernäs H.Direct estimation of the in vivo dissolution of spironolacton, in two par-ticle sizes, using single pass perfusion technique (loc-I.Gut). Eur JPharm Sci 2001;12:239-250.

Christensen KL, Pedersen GP, Kristensen HG. Preparation of redis-persible dry emulsions by spray drying. Int J Pharm 2001;212:187-194.

Christensen KL, Pedersen GP, Kristensen HG. Technical optimiza-tion of redispersible dry emulsions. Int J Pharm 2001;212:195-202.

Davidsen J, Vermehren C, Frokjaer S, Mouritsen OG, Jørgensen,K. Drug delivery by phospholipase A2 degradable liposomes. Int JPharm 2001;214:67-69.

Davidsen J, Vermehren C, Frøkjær S, Mouritsen OG, Jørgensen K.Enzymatic degradation of polymer Covered SOPC-liposomes in rela-tion to drug delivery. Advances in Colloid and Interface Science 89-90.2001: 303-311.

Friedrichsen G, Nielsen CU, Steffansen B, *Begtrup M. Model pro-drugs for the intestinal peptide transporter. A synthetic approach forcoupling of hydroxy-containing compounds to dipeptides. Eu J PharmSci 2001;14:13-19.

Hahn TW, Henneberg SW, Holm-Knudsen RJ, Eriksen K,Rasmussen SN, Rasmussen M. Pharmacokinetics of rectal paraceta-mol after repeated dosing in children. BJA 2000;85(4):512-9.

Hansen M, Christrup LL, Jarløv JO, Kampmann JP, Bonde J.Gentamicin dosing in critically ill patients Acta Anaesthesiol Scand2001;45(6):734-740.

Holm R, Müllertz A, Høy GE, Kristensen HG. Comparison of the to-tal bioavailability and the lymphatic absorption of halofantrine fromthree different unsaturated triglycerides in lymph-canullated conciousrats. Eur J Pharmci 2001;14:331-338.

Holm P, Schæfer T, Larsen C. End-point detection in a wet granula-tion process. Pharm Dev Technol 2001;6:151-162.

Holm R, Müllertz A, Pedersen GP, Kristensen HG. Comparison ofthe lymphatic transport of halofantrine administered in disperse sys-tems containing three different unsaturated fatty acids. Pharm Res2001;18:1299-1304.

Johansen A, Schæfer T. Effects of interactions between powder par-ticle size and binder viscosity on agglomerate growth mechanisms in ahigh shear mixer. Eur J Pharm Sci 2001;12:297-309.

Johansen A, Schæfer T. Effects of physical properties of powder par-ticles on binder liquid requirement and agglomerate growth mecha-nisms in a high shear mixer. Eur J Pharm Sci 2001;14:135-147.

Kristensen J, Schæfer T, Kleinebudde P. Direct pelletization in a ro-tary processor controlled by torque measurements. II: Effects ofchanges in the content of microcrystalline cellulose. AAPS Pharmsci. 2(3) (2000) article 24.

Lindhardt K, Ravn C, Gizurarson S, Bechgaard E. Intranasal ab-sorption of buprenorphine - in vivo bioavailability study in sheep. Int JPharm 2000;205:159-63.

Lindhardt K, Bagger M, Andreasen KH, Bechgaard, E. Intranasalbioavailability of buprenorphine in rabbit correlated to sheep and man.Int J Pharm 2001;217:121-26.

Lindhardt K, Gizurarson S, Stefánson SB, Òlafsson DR,Bechgaard EB. Electroencephalographic effects and serum concen-trations after intranasal and intravenous administration of diazepam tohealthy volunteers. Br J Clin Pharmacol 2001;52:521-27.

Luukkonen P, Schæfer T, Podczeck F, Newton M, Hellén L,Yliruusi J. Characterization of microcrystalline cellulose and silicifiedmicrocrystalline cellulose wet masses using a powder rheometer. Eur JPharm Sci 2001;13:143-149.

Møller-Sonnergaard J. Investigation of a new mathematical model forcompression of pharmaceutical powders. Eur. J Pharm Sci2001;14:149-157.

PUBLICATIONS

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Nielsen CU, Andersen R, Brodin B, Frokjaer S, Steffansen B.Model prodrugs for the intestinal oligopeptide transporter: model re-lease in aqueous solution and in various biological media. J ControlRel 2001;73:21-30.

Nielsen CU, Amstrup JSteffansen, B Frokjaer, S and Brodin, B.Epidermal growth factor inhibits glycylsarcosine transport and hPepT1expression in a human intestinal cell line, Am J Physiol GastrointestLiver Physiol 2001;281:G191-G199.

Nielsen L, Frokjaer S, Carpenter JF, Brange J. Studies of the struc-ture of insulin fibrils by Fourier transform infrared (FTIR) spectroscopyand electron microscopy, J Pharm Sci 2001;90:29-37.

Nielsen CU, Andersen R, Brodin B, Frokjaer S, Taub ME,Steffansen B. Dipeptide model prodrugs for the intestinal oligoepptidetransporter. Affinity for, and transport via hPepT1 in the human intesti-nal Caco-2 cell line. J Control Rel 2001;76:129-138.

Nielsen CU, Andersen R, Brodin B, Frokjaer S, Steffansen B.Model prodrugs for the intestinal oligopeptide transporter: model drugrelease in aqueous solution and in various biological media. J ControlRel 2001;73:21-30.

Nielsen CU, Amstrup J, Steffansen B, Frokjaer S, Brodin B.Epidermal growth factor (EGF) inhibits glycylsarcosine (Gly-Sar) trans-port and hPepT1 expression in human intestinal cell line. Am J PhysiolGastrointest Liver Physiol 2001;281:G191-G199.

Nielsen PB, Müllertz A, Norling T, Kristensen HG. The effect of �-tocopherol on the in vitro solubilisation of lipophilic drugs. Int J Pharm 2001;222:217-224.

Nielsen PB, Müllertz A, Norling T, Kristensen H.G. Comparison ofthe lymphatic transport of a lipophilic drug from vehicles containing �-tocopherol and/or triglyceride in rats. J Pharm Pharmacol2001;53:1439-144.

Nielsen L, Khurana R, Coats A, Frokjaer S, Brange J, Vyas S,Uversky VN, Fink AL. The effect of enviromental factors on the kinet-ics of insulin fibril formation: Elucidation of the molecular mechanism.Biochemistry 2001;40:6036-6046.

Nielsen L, Frokjaer S, Brange J, Uversky VN, Fink AL. Probing theMechanism of Insulin Fibril Formation with Insulin Mutants.Biochemistry 2001;40:6036-6046.

Nielsen HW, Bechgaard E, Twile B, Didriksen E, Almtorp GT.Solubilisation and stability of bumetanide in vehicles for intranasal ad-ministration, a pilot study. Pharm Devel Technol 2001;6(2):145-49.

Overgaard ABA, Højsted J, Hansen R, Møller-Sonnergaard J,Christrup LL. Patients evalution of shape, size and colour of soliddosage forms. Pharm World Sci 2001;23(5):185-188.

Overgaard ABA, Moeller-Sonnergaard J, Christrup LL, Hoejsted J,Hansen R. Patients’ evaluation of shape, size and colour of soliddosage forms. Pharm World Sci 2001;23:185-188.

Pedersen TB, Sabra MC, Frokjaer S, Mouritsen OG, Jørgensen K.Association of Acylated cationic Deca-peptides with DPPS-DPPCLipid Membranes, Chem Phys Lipids 2001;113:83-95.

Pedersen TB, Frokjaer S, Mouritsen OM, Jørgensen K. A calori-metric Study of Phoshocholine membranes mixed with desmopressinand its diacylated prodrug derivative (DDP), Int J Pharm (in press).

Pedersen TB, Sabra MC, Frokjaer S, Mouritsen OG, Jørgensen K.Association of an acylated model peptide with DPPC-DPPS lipidmembranes, Int J Pharm 2001;214:77-81.

Petersen FJ, Wørts O, Schæfer T, Sojka PE. Effervescent atomiza-tion of aqueous polymer solutions and dispersions. Pharm DevTechnol 2001;6:133-142.

Rømsing J, Østergaard D, Senderovitz T, Drozdziewicz D, SonneJ, Ravn G. Pharmacokinetics of oral diclofenac and acetaminophen inchildren after surgery. Paed Anaesth 2001;11:205-213.

Rømsing J, Mysager S, Vilmann P, Sonne J, Larsen NE,Østergaard D. Postoperative analgesia is not different after local vssystemic administration of meloxicam in patients undergoing inguinalhernia repair. Can J Anesth 2001;48:978-98.

Schæfer T. Growth mechanisms in melt agglomeration in high shearmixers. Powder Technol 2001;117:68-82.

Seo A, Schæfer T. Melt agglomeration with polyethylene glycol beadsat a low impeller speed in a high shear mixer. Eur J Pharm Biopharm2001;52:315-325.

Vermehren C, Jørgensen K, Schiffelers R, Frokjaer S. Activity ofmammalian secreted phospholipase A2 from inflammatory peritonealfluid towards PEG-liposomes. Early indications. Int J Pharmaceut2001;214:93-98.

Zangenberg NH, Müllertz A, Kristensen HG, Hovgaard L. A dynam-ic in vitro lipolysis model. Part I. Controlling the rate of lipolysis by con-tinous addition of calcium. Eur J Pharm Sci 2001;14:115-122.

Zangenberg NH, Müllertz A, Kristensen HG, Hovgaard L. A dynam-ic in vitro lipolysis model. Part II. Dissolution of probucol and danazol. Eur J Pharm Sci 2001;14:237-244.

PHD THESES

Andersen G. Relations between morphine metabolism, pain and sideeffects during long term treatment.

Bjerregaard S. Parenteral water-in-oil emulsions as sustaquined re-lease systems for hydrophilic compounds.

Hahn TW. Acetaminophen (Paracetamol). Pharmacokinetics andAnalgetic Effect in Postoperative Patients.

Lindhardt K. Nasal drug delivery. Applicability of nasal administrationfor systemic delivery, preferentially concerning acute treatment.

Kristensen J. Direct pelletization in rotary Processors.

Nielsen CU. Intestinal Peptide Transporter mediated Drug delivery us-ing Stabilized Dipeptide Pro-moieties: Affinity, Transport, Drug Releaseand Regulation.

Nielsen BP. Tocopherol as an oral drug delivery system.

Qvist MH. Chemical Permeations Enhancers in Transdermal DrugDelivery Systems.

Wiberg-Larsson BI. Comminution of particulate solids in a MicrosRing Mill.

Zangenberg NH. Development of a dynamic lipolysis model

OTHER PUBLICATIONS

Andersen R. Stabillitet og transport af modelprodrug designet til denintestinale oligopeptidtransportør. [Stabillity and transport of a modelprodrug designed for the intestinal oligopeptide transporter] DanmarksFarmaceutiske Højskole 2000.

Bagger MA, Beckgaard E. Genvej til hjernen via næsen. [Short cut tothe brain via the nose] Lægemiddelforskning 2001;24-25.

Brodin B, Nielsen CU, Steffansen B, Froklaer S. Ind gennem tarm-cellerne via naturlige optagemekanismer [Drug absorption via carrierprotein in the small intenstine] Lægemiddelforskning 2000;20-21.


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Foged C, Brodin B, Frokjaer S. Optagelse af nye vacciner i kroppensimmunceller. [Uptake of new types of vaccines in denoritic cells]Lægemiddelforskning 2000;32-33.

Hahn TW, Rasmussen SN, Rasmussen M. Korrekt dosering ved be-handling af børns smerter. [The right dosing in pain management inchildren] Lægemiddelforskning 2000;8-9.

Heydenreich-Winther A, Bryder K, Fomsgaard A, Hovgaard L.DNA-vacciner: Stort potentiale – store udfordringer. [DNA-vaccines:Potentials and challenges] Lægemiddelforskning 2000;4-5.

Holm R, Müllerts A, Kristensen HG. Ind gennem tarmens lymfesys-tem. [Lymphatic transport of drugs] Lægemiddelforskning 2001;26-27.

Høst J, Jørgensen FS, Christensen IT, Hovgaard L, Frøkjaer S.Computeren er medicinalindustriens krystalkugle. [The computer is thecrystal ball for medicinal industry] Lægemiddelforskning 2001;28-29.

Jacobsen J, Rassing MR. Ind via mundslimhinden med svag strøm.[Cromucosal drug delivery applying iontophoresis]Lægemiddelforskning 2000;18-19.

Pedersen TB, Frokjaer S, Mouritsen OG, Jørgensen K.Membranforankring og peptiders terapeutiske effekt. [Membrane asso-ciation in relation to the terapeutic effect and peptides]Lægemiddelforskning 2000;22-23.

Petersen, F.J., Kristensen, H.G., Wørts, O., and Schæfer, T. Nylovende teknik til forstøvning af lægemidler. [A new technique for at-omization of luquids] Lægemiddelforskning 2000;14-15.

Nielsen LH. Udvikling af en fysisk kemisk model af blod-hjerne barri-eren. [A physico-chemical blood brain barrierer model developmentstudies] Danmarks Farmaceutiske Højskole /NeuroSearch, September2000.

Sønderkær S, Hansen LL, Flink J, Frokjaer S. Proteiner somlægemidler. [Proteins as drugs] Lægemiddelforskning 2001;16-17.

PATENT APPLICATIONS

Jorgensen K, Davidsen J, Vermehren C, Frokjaer S. MouritsenOG. Lipid-based drug delivery systems containing phospholipase A2degradable lipid derivatives and the therapeutic uses thereof. WO01/58910.

Jorgensen K, Davidsen J, Vermehren C, Frokjaer S, MouritsenOG. Lipid-based drug delivery systems containing phospholipase A2degradable lipid derivatives for topical application to the skin WO01/76555.

Jorgensen K, Davidsen J, Vermehren C, Frokjaer S, MouritsenOG. Lipid-based drug delivery systems for targeting diagnosticsagents. WO 01/76644.

Jorgensen K, Davidsen J, Vermehren C, Frokjaer S, MouritsenOG. Lipid-based drug delivery systems containing phospholipase A2degradable lipid derivatives for medical use against parasitic infections.WO 01/76556.


Alsbo CW, Kristiansen U, Møller FM, Hansen SL, Johansen FF.GABAA receptor subunit interactions important for benzodiazepine andzinc modulation: a patch-clamp and single cell RT-PCR study. Eur JNeurosci 2001;13:1673-1682.

Ashina M, Bendtsen L, Jensen R, Jansen-Olesen I, Schifter S,Olesen J. Plasma levels of calcitonin gene-related peptide in chronictension-type headache. Neurology 2000;55:1335-1340.

Banke TG, Greenwood J, Christensen JK, Liljefors T, SchousboeA, Pickering DS. Identification of amino acid residues in GluR1 re-sponsible for ligands binding and desensitization. J Neurosci2001;21:3052-3062.

Campiani G, Morelli E, Nacci V, Fattorusso C, Ramunno A,Novellino E, Greenwood J, Liljefors T, Griffiths R, Sinclair C,Reavy H, Kristensen AS, Pickering DS, Schousboe A, Cagnotto A,Fumagalli E, Mennini T. Characterization of the 1H-cyclopentapyrimi-dine-2,4(1H,3H)-dione derivative (S)-CPW399, as a novel, potent andsubtype-selective AMPA receptor full agonist with partial desensitiza-tion properties. J Med Chem 2001 in press.

Edvinsson L, Sams A, Jansen-Olesen I, Tajti J, Kane SA, RutledgeRZ, Koblan KS, Longmore J. Characterization of the effects of anon-peptide CGRP receptor antagonist in SK-N-MC cells and isolatedhuman cerebral arteries. Eur J Pharmacol 2001;415:39-44.

Elster L, Kristiansen U, Pickering D, Olsen RW, Schousboe A.Molecular determinants of desensitization and assembly of thechimeric GABAA receptor subunits (�1/�2) and (�2/�1) in combinationwith �2 and �2. Neurochem Int 2001;38:581-592.

Eltorp CT, Jansen-Olesen I, Hansen AJ. Release of CGRP fromguinea pig dura mater in vitro is inhibited by sumatriptan but unaffect-ed by nitric oxide. Cephalalgia 2000;20:838-844.

Engberg J, Jensen BL, Yenidunya AF, Brandt K, Riise E. Phage-display libraries of murine antibody Fab fragments. Lab manual on an-tibody engineering (ed. S. Dübel). Springer Verlag 2001;ISBN 3-540-41354:65-92.

Engberg J, Yenidunya AF, Clausen R, Jensen BL, Sørensen P,Kops P, Riise E. Human recombinant Fab antibodies with T cell re-ceptor-like specificities generated from phage display libraries.Methods in Molecular Medicine (eds. Krauss, J and Welschof, M.)Humana Press (in Press) 2001.

Frølund B, Tagmose L, Liljefors T, Stensbøl TB, Engblom C,Kristiansen U, Krogsgaard-Larsen P. A novel class of potent 3-isox-azolol GABAA antagonists: Design, synthesis and pharmacology. JMed Chem 2000;43:4930-4933.

Gegelashvili G, Robinson MB, Trotti D, Rauen T. Regulation of glu-tamate transporters in health and disease. Progress in Brain2001;132:267-286.

Gegelashvili G. Glutamate transporters: Adding new tunes to theneuron-glia orchestra. Neurochemistry news 2001;1:65-68.

Hansen SL, Ebert B, Kristiansen U. Effects of GABAA receptor par-tial agonists in primary cultures of cerebellar granule neurones andcerebral cortical neurones reflect different subunit compositions. Br JPharmacol 2001;133:539-549.

Hansen SH, Moesgaard B, Hansen HH, Petersen G. When andwhere are N-acyl-ethanolamine phospholipids and anandamideformed? Wld Rev Nutr Diet 2000;88:223-227.

Hansen HH, Ikonomidou C, Bittigau P, Hansen SH, Hansen HS.Accumulation of the anandamide precursor and other N-acyletha-nolamine phospholipids in infant rat models of in vivo necrotic andapoptotic neuronal death. J Neurochem 2001;76:39-46.

Hansen HH, Schmid PC, Bittigau P, Lastres-Becker I, BerrenderoF, Manzanares J, Ikonomidou C, Schmid HHO, Ramos JA,Fernándes-Ruiz JJ, Hansen HS. Anandamide, but not 2-arachi-donoylglycerol, accumulates during in vivo neurodegeneration. JNeurochem 2001;78:1415-1427.

Hansen SL, Ebert B, Fjalland B, Kristiansen U. Effects of GABA(A)receptor partial agonists in primary cultures of cerebellar granule neu-rones and cerebral cortical neurones reflect different receptor subunitcompositions. Br J Pharmacol 2001;133(4):539-549.

PUBLICATIONS

PAGE 115

Jansen-Olesen I, Kaarill L, Edvinsson L. Characterization of CGRP-1 receptors in the guinea pig basilar artery. Eur J Pharmacol2001;414:249-258.

Jensen JB, Lund TM, Timmermann DB, Schousboe A, PickeringDS. Role of GluR2 expression in AMPA induced toxicity in culturedmurine cerebral cortical neurones. J Neurosci Res 2001;65:267-277.

Johansen T, Hansen HS, Richelsen B, Malmlöf K. The obeseGöttingen minipig as a model of the metabolic syndrome: Dietary ef-fects on obesity, insulin sensitivity and growth hormone profile. JComp Med 2001;51:150-155.

Kruuse C, Rybalkin S, Khurana TS, Jansen-Olesen I, Olesen J,Edvinsson L. The role of cGMP related phosphodiesterases, PDE1and PDE5, in cerebral artery dilatation. Eur J Pharmacol 2001;420:55-65.

Larsen AH, Frandsen Aa, Treiman M. Upregulation of the SERCA-type Ca2+ pump activity in response to endoplasmic reticulum stress inPC12 cells. BMC Biochemistry 2001;2-4.

Lauritzen L, Hansen HS, Jørgensen MH, Michaelsen KF. The es-sentiality of long chains n-3 fatty acids in relation to postnatal develop-ment and function of the brain and retina. Prog Lipid Res 2000;40:1-94.

Paschen W, Frandsen Aa. Endoplasmic Dysfunction - a common de-nominator for cell injury in acute and degenerative diseases of thebrain?, Invited review J Neurochem 2001;79:719-725.

Reuter U, Bolay H, Jansen Olesen I, Chiarugi A, Sanches del RioM, Letourneau R, Theoharides TC, Weaber C, Moskowitz MA.Delayed inflammation in rat meanings: Implication for migraine patho-physiology. Brain 2001;124:2490-2502.

Sams Nielsen A, Ørskov C, Jansen Olesen I. Evidence for CGRPuptake in perivascular capsaicin sensitive nerve fibres. Br J Pharmacol2001;132:1145-1153.

Sams A, Knyiha´r-Csillik E, Engberg J, Szok D, Tajti J, Bodi I,Edvinsson L, Vecsei L, Jansen Olesen I. Calcitonin gene-relatedpeptide and adrenomedullin receptor populations in human lenticulstri-ate arteries: in vitro pharmacological and molecular investigations indifferent artery sizes. Eur J Pharmacol 2000;408:183-193.

Schousboe A. Pharmacological and functional characterization ofastrocytic GABA transport: A short review. Neurochem Res2000;25:1241-1244.

Schousboe A, Kanner B. GABA transporters: functional and pharma-cological properties. In: Glutamate and GABA Receptors andTransporters (J Egebjerg, A. Schousboe and P. Krogsgaard-Larsen,eds.). Taylor & Francis Publ. 2002;337-349.

Schousboe A, Waagepetersen HS. Glial cell biology. In: The New-born Brain - Scientific Basis and Clinical Applications (H. Lagercrantz,P. Evrard, M. Hanson and C. Roedeck, eds.). Cambridge UniversityPress. 2002 in press.

Schousboe A, Hansen GH, Carlson BX. Amino acid neurotransmit-ters as developmental signals. In: Brain and Behaviour in HumanDevelopment (Kalveboer, A.F. and Gramsbergen, A eds.). KluwerAcademic Publ The Netherlands. 2001;185-197.

Sheykhzade M, Nyborg NCB. Mechanism of CGRP-induced relax-ation in rat intramural coronary arteries. Br J Pharmacol2001;132:1235-1246.

Timmermann DB, Lund TM, Belhage B, Schousboe A. Localizationand pharmacological characterization of voltage dependent calciumchannels in cultured neocortical neurones. Int J Dev Neurosci2001;19:1-10.

Timmermann DB, Westenbrook RE, Schousboe A, Catterall WA.Distribution of high voltage-activated calcium channels in culturedGABAergic neurones from mouse cerebral cortex. J Neurosci Res2002;67 in press.

Waagepetersen HS, Qu H Schousboe A, Sonnewald U. Elucidationof the quantitative significance of pyruvate carboxylation in culteredcerebellar neurons and astrocytes. J Neurosci Res 2001 in press.

Waagepetersen HS, Shimamoto K, Schousboe A. Comparison ofeffects of DL-threo-�-benzyloxyaspartate (DL-TBOA) and L-trans-pyrrolidine-2,4-dicarboxylate (t-2,4-PDC) on uptake and release of[3H]-aspartate in astrocytes and glutamatergic neurons. NeurochemRes 2001;26:661-666.

Waagepetersen HS, Sonnewald U, Gegelashvili G, Larsson OM,Schousboe A. Metabolic distinction between vesicular and cytosolicGABA in cultured GABAergic neurones using 13C MRS. J NeurosciRes 2001;63:347-355.

Waagepetersen HS, Sonnewald U, Larsson OM, Schousboe A.Multiple compartments with different metabolic characteristics are in-volved in biosynthesis of intracellular and released glutamine and cit-rate in astrocytes. Glia 2001;35:246-252.

Zaganas I, Waagepetersen HS, Georgopoupolos P, Sonnewald U,Plaitakis A, Schousboe A. Differential expression of glutamate dehy-drogenase in cultured neurons and astrocytes from mouse cerebellumand cerebral cortex. J Neurosci Res 2001 in press.

PHD THESES

Hansen H.H. The impact of brain injury: Involvement of the system ofendocannabinoids ligands and receptors.

Sams-Nielsen A. Characterization of CGRP induced effects in humanand guinea pig cerebral arteries.

Sheykhzade M. Characterization of calcitonin gene-related peptide re-ceptor subtype and function in rat coronary arteries.

Timmermann D. Subcellular localization and pharmacological charac-terization of violtage-gated calcium channels in cultured neocorticalneurones.

OTHER PUBLICATIONS

Frølund SL, Kristiansen U, Stensbøl TB, Krogsgaard-Larsen P. Nynøgle til behandling af skizofreni? [A new strategy for treatment ofschizophrenia?] Lægemiddelforskning 2000;24-25.

Hansen HH, Hansen SH, Hansen HS. Hjernens cannabis-lignendestoffer modvirker celledød. [The endogenous cannabis-like com-pounds prevents cellular death]. Lægemiddelforskning 2000;26-27.

Hansen HS. Endocannabinoider og deres fosfolipidforstadier.Carlsbergfondet - Årsskrift [Endocannabinoids and their Phospholipidsprecursors]. Carlsbergfoundation - Yearbook 2001;42-47.

Lund TM, Christensen E, Schousboe A, Lund AM. Stofskifte syg-domme - fra gen til terapi. Lægemiddelforskning [Metabolic diseases -from gene to therapy]. Lægemiddelforskning 2001;12-13.

Moesby L, Tommerup L, Hansen EW, Christensen JD. Kontrol aflægemidler for feberfremkaldende stoffer. Lægemiddelforskning[Control of pharmaceutical products for fever inducing substances].Lægemiddelforskning 2000:12-13.


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PEER REVIEW PUBLICATIONS

Almarsdóttir AB, Morgall JM, Grímsson A. Professional responsibili-ty for the patient’s welfare - is it possible to legislate pharmaceuticalcare? J Soc Adm Pharm 2001;18:45-50.

Bissell P, Stig Haugbølle L, Morgall Traulsen J. An introduction tosociology – and what it can do for pharmacy practice research. Int JPharm Pract 2001;9:289-95.

Björnsdóttir I, Hansen EH. Telephone prescribing of antibiotics:General practitioners’ views and reflection. Eur J Public Health2001;11:260-3.

Karkee SB. Quality of drug provision from a philosophy of scienceperspective. Bulletin of Nepal Pharmaceutical Association 2000;11:7-12.

Karkee SB, Gyldmark M. Study setting in a research on drug provi-sion at primary health care. GPAN Bulletin 2001;(5):31-40.

Karkee SB, Hansen EH. Approaches to quality in drug provision.GPAN Bulletin 2000;(4):29-34.

Karkee SB, Hansen EH. Literature review on provision of antibacteri-als in primary health care in Nepal. Bulletin of Nepal PharmaceuticalAssociation 2001;12:35-46.

Morgall Traulsen J, Björnsdóttir I. Confidentiality – an issue forwhom? Focus group interviews with the lay public in Iceland. In:Institut für Technikfolgenabschätzung und Systemanalyse, editors.Innovations for an e-society. Challenges for technology assessment.Federal Ministry of Education and Research 2001. Available from: http://www.itas.fzk.de/e-society/preprints/contents.pdf(appears in Session 4: “e-health”).

Møldrup C, Morgall JM. Risks of future drugs: A Danish expertDelphi. Technological Forecasting and Social Change 2001;67:273-89.

Møldrup C, Morgall JM. Risk society reconsidered in a drug context– the emergence of medically enhanced normality. Health, Risk &Society 2001;3:59-74.

Møldrup C, Morgall JM, Almarsdóttir A. Citizens involvement in drugresearch and development - Danish citizens Delphi. Foresight2000;5:452-62.

Nørgaard LS, Morgall JM. The social construction of a drug interac-tion screening program – expectations and change in Danish pharma-cy practice. J Soc Adm Pharm 2000;17:110-17.

Nørgaard LS, Sørensen EW, Morgall JM. Social constructivist analy-sis of a patient medication record experiment – why a good idea andgood intentions are not enough. Int J Pharm Pract 2000;8:237-46.

Skinhoj KT, Larsson S, Helweg-Joergensen S, Hansen EH.Experiences of long-term tranquillizer use: A psychodynamic perspec-tive. Substance Use & Misuse 2001;36(9&10):1165-86.

Trap B, Todd CH, Moore H, Laing R. The impact of supervision onstock management and adherence to treatment guidelines: a random-ized controlled trial. Health Policy and Planning 2001;16:273-80.

PHD THESES

Knudsen P. The experience of younger women with SSRI antidepres-sants - a user perspective. Copenhagen: The Royal Danish School ofPharmacy, Department of Social Pharmacy 2001.

Ndekha A. Strengthening community participation in schistosomiasiscontrol: lessons from the Guruve District (Zimbabwe) schistosomiasiscontrol programme using Phytolacca dodecandra (a plant mollusci-cide). Copenhagen: The Royal Danish School of Pharmacy,Department of Social Pharmacy 2001.

OTHER PUBLICATIONS

Andersen C, Hansen EH, Morgall J. Pharmaceutical care – Status inDanish community pharmacies. Farmaceuten 2000;12(19):19-20.

Brendstrup E, Launsø L, Langgaard H. Kræftpatienters alternativevalg. [Cancer patients’ alternative choice]. Mit Helbred 2001;6:4-9 andSocial Kritik 2001;76:44-51.

Grum C, Launsø L. Giv plads til forskning i alternativ behandling.[Make space for research on alternative treatment]. Feature article.Danmarks Amtsråd 2001;(Aug):18-19.

Hansen EH, editor. Lægemiddeldage 2000. [The Medical DaysConference 2000]. Er lægemidler sund økonomi? [Are drugs value formoney?]. Farmaceuten 2000;12(19):18-25.

Hansen EH, Holstein BE, Due P. Social class variation in medicineuse among adolescents. Farmakoepi-Nyt 2001;(13):7.

Hansen EH, Holstein BE, Due P, Currie C. Medicine use among 11-15-year-old girls and boys in 28 countries. Farmakoepi-Nyt2001;(13):8.

Hansen EH, Lunde P-K. Utvärdering av NEPIs verksamhet 1995 -2000. Utvärderingsrapport februari 2001. [Evaluation of NEPI’s activi-ties 1995-2000]. Evaluation Report February 2001. Stockholm: InNEPI Annual Report 2000. p. 3-7. Available from: http://www.nepi.net/

Knudsen P, Hansen EH, Morgall JM. Yngre kvinders brug af SSRI.[Young women’s use of SSRI]. Farmaceuten 2000;12(19):24-5.

Knudsen P, Hansen EH, Morgall JM. Fra ilden til asken med antide-pressiv medicin. [From the fire into the frying pan with antidepressantmedicine]. Lægemiddelforskning 2000:34-5.

Kruse PR, Møller N. De danske apotekers historie; vol 7. [The historyof the Danish pharmacies; vol 7]. København: DanmarksApotekerforening; 2001 (752 pp).

Kruse PR, Møller N. Apotekervæsenets historie i Danmark. [The his-tory of the pharmacy system in Denmark]. København: DanmarksApotekerforening; 2001 (152 pp).

Langgaard H, Launsø L, Haugaard C. Main themes in research onunconventional cancer treatment. A literature study. Townsend Letterfor Doctors and Patients 2001;(Aug/Sept):57-66.

Larsen JB. Kend spillets regler. [Know the rules of the game].Farmaceuten 2001;13(16):4-5.

Launsø L. FVUK – et frø af kræftforeningen Tidslerne. [FVUK - A seedof the cancer association The Thistle]. Tidslerne 2001;(1):19-22.

Launsø L. Døre der åbner sig: Om grænseoverskridende læger og far-maceuter i det danske sundhedsvæsen. [Doors opening: About physi-cians and pharmacists as boundary walkers in the Danish health caresystem]. Højbjerg: Forlaget Hovedland 2001 (196 pp).

Launsø L. Omstridt behandling uden mirakler. [Controversial treatmentwithout miracles] 2’eren. Scleroseforeningen 2001;(June 6):8-10 andTidsskrift for Norsk Forening for Multippel Sklerose 2001;2:6-8.

Launsø L, Langgaard H. Ukonventionel kræftbehandling I. Præmisserfor kræftbehandling og forskning. [Unconventional cancer treatment I.The premises for treatment and research]. Månedsskrift for PraktiskLægegerning 2001;79:957-60.

PUBLICATIONS

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Launsø L, Langgaard H. Ukonventionel kræftbehandling II.Kræftpatienters handlerum - et medicinsk og sociologisk forsknings-felt. [Unconventional cancer treatment II. Cancer patients’ scope of ac-tion – a medical-sociological field of research]. Månedsskrift forPraktisk Lægegerning 2001;79:1043-50.

Launsø L, Langgaard H. Den selvvisiterende patient. Om forståelse afbrug og virkninger af ukonventionel og konventionel kræftbehandling.[The self-referring patient. Understanding of cancer patients’ usageand experienced outcomes of unconventional treatment]. Social Kritik2000;68:69 -78.

Launsø L, Rieper O. Forskning om og med mennesker - forskn-ingstyper og forskningsmetoder i samfundsforskning. [Research aboutand with human beings – modes of research and research methods insocial science]. Copenhagen: Nyt Nordisk Forlag; 2000, 4th edition(236 pp).

Lindholm K, Toft T, Larsen LAA, Sørensen EW, Nørgaard LS.Development of advice to type 2 diabetics by community pharmacies.Abstract. Pharmacology & Toxicology 2001;89(Suppl 1):109.

Møldrup C. Skræddersyede lægemidler til individuelle genomer.[Tailor-made drugs for individual genomes]. Lægemiddelforskning2001:10-11.

Møldrup C. Fremtidens medicin er skræddersyet. [Future drugs aretailor-made]. Helse 2001;11:26-7.

Møldrup C. Vil doping være forbeholdt idrætsudøvere i fremtiden?[Will doping only be a part of sports in the future?]. Fremtidsorientering2001;3:8-11.

Møldrup C. Skal doping være forbeholdt idrætsudøvere? [Shoulddoping only be a part of sports?]. In: Hvorfor er det ikke tilladt atbruge doping? [Why is doping not allowed?]. Anti Doping Danmarksidekonference; 2001. p. 20-1. Available from: http://www.doping.dk

Møldrup C. Medicin til alle og mod alt. [Drugs to everybody and foreverything]. Helse 2000;(10):79,81.

Møldrup C. Fremtidens medicinske optimerede krop. [The medicaloptimized body of the future]. Feature article. Jyllands-Posten 2000Sept 14.

Nyland N, Donner JE, Christensen BC, Harvald B, Kruse PR,Permin H, editors. Dansk Medicinhistorisk Årbog 2000; vol 28.[Danish Medical History Yearbook 2000; vol 28]. København, Odense,Århus: Dansk Medicinsk-Historisk Selskab, Medicinsk HistoriskSelskab på Fyn, Jysk Medicinhistorisk Selskab; 2000 (238 p).

Nørgaard LS, Sørensen EW, Toft T, Larsen LA. Systematisk indsam-ling af data om patienters lægemiddelrelaterede viden, holdninger oghandlinger. (Systematic collection of data on patients’ drug relatedknowledge, attitudes and actions). Fynske Læger 2001 May:41-2.

Permin H, Christensen BC, Harvald B, Kruse PR, Nyland N,Petersen CB, editors. Dansk Medicinhistorisk Årbog 2001; vol 29.[Danish Medical History Yearbook 2001; vol 29]. København, Odense,Århus: Dansk Medicinsk-Historisk Selskab, Medicinsk HistoriskSelskab på Fyn, Jysk Medicinhistorisk Selskab; 2001 (261 p).

Rossing C, Hansen EH, Morgall JM. Farmaceutisk omsorg påapotekerne. [Pharmaceutical care in community pharmacies].Lægemiddelforskning 2001:38-9.

Sørensen EW. Development of pharmacy practice – with special fo-cus on implementation and learning processes. Abstract. Faculty ofPharmacy, Sofia, Bulgaria: Phuture. International PharmaceuticalStudents’ Federation 2000;(Suppl 1):12.

Timm H, Hansen HP, Morgall JM, Sigmund H. Patienten – felt-arbejde, interview- og spørgeskemaundersøgelser. [The patient - fieldwork, interview and questionnaire studies]. In: Kristensen FB, HørderM, Poulsen PB, editors. Metodehåndbog for Medicinsk


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Teknologivurdering. [Methodology manual for medical technology as-sessment]. Copenhagen: Centre for Evaluation and Health TechnologyAssessment; 2001. p. 36-55. (Two versions: Danish and English).

Toft T, Sørensen EW, Andersen U, Gundersen B, Herborg H,Jensen MJ et al. Development of advice to angina pectoris patientsby community pharmacies. Farmaceuten 2000;12(19):21-2.

Toft T, Lindholm K, Larsen LAA, Sørensen EW, Nørgaard LS.Development of advice to angina pectoris patients by communitypharmacies. Pharmacology & Toxicology 2001;89(Suppl 1):147.

Wilkenschildt M, Kruse PR. Kejserinden og hendes rejsende apotek.[The empress and her travelling pharmacy]. In: Wilkenschildt M.Kongelige klenodier og kuriositeter. [Royal treasures and curios].København: Lindhardt og Ringhof; 2001. p. 189-93, 232-42.

THE DANISH PHARMACEUTICAL LIBRARY

Munck J. Glade miljøkemikere og biofarmaceuter. [Contented environ-mental chemists and biopharmacists.] Plexus 2000;32(4):3-5.

Munck J. Klinisk farmaci. [Clinical pharmacy.] Plexus 2000;32(4):6-7.

Munck J. Information, IT og de nye studerende på DanmarksFarmaceutiske Højskole. [Information, IT and new students at RoyalDanish School of Pharmacy.] Plexus 2000;32(5):3-7.

Munck J. Ungt blod til naturstofkemigruppen. [New talent for naturalproduct chemistry group.] Plexus 2000;32(6):9-10

Munck J. Sven Erik Jørgensen – forskningsprofessor. [Sven ErikJørgensen – research professor.] Plexus 2000;32(6):11.

Munck J. Massivt ønske om aktiv personalepolitik fra Højskolens lek-torer. [Associate professors strongly urge active personnel policy forRoyal Danish School of Pharmacy.] Plexus 2001;33(1):3-6.

Munck J. Højskolens nye rektor. [New rector for Royal Danish Schoolof Pharmacy.] Plexus 2001;33(2):3-6.

Munck J. Aftale om ny løn for laboranterne. [New wage agreement forlaboratory technicians.] Plexus 2001;33(2):14-15.

Munck J. Et rektorat takker af. [A rector steps down.] Plexus2001;33(3):3-5.

Munck J. Tanker ved et sceneskifte. [Reflections on a change ofscene.] Plexus 2001;33(3):6-9.

Munck J. Ingen nye centerbevillinger til DFH. [No new centre fundingfor Royal Danish School of Pharmacy.] Plexus 2001;33(3):10.

Munck J. De Danske Apotekers Historie. [The History of DanishPharmacies.] Plexus 2001;33(3):11-13.

Munck J. Ny institutstruktur? [New departmental structure?] Plexus2001;33(4):3-4.

Munck J. Specialistuddannelsen i apotekspraksis. [Specialisation inpharmacy practice.] Plexus 2001;33(4):8-10.

Munck J. Studenternetværket. [The Student Network.] Plexus2001;33(4):12-13.

Munck J. Ny webmaster. [New webmaster.] Plexus 2001;33(4):30.

Munck J. Ole Bjerrum ny professor i farmakologi. [Ole Bjerrum newprofessor of pharmacology.] Plexus 2001;33(4):32-33.

Munck J. Hvad er der galt med eksamenssystemet? [What is wrongwith the exam system?] Plexus 2001;33(5):6-9.

Munck J. Skal nye farmaceutuddannelser løse behovet for flere farma-ceuter? [Should new pharmacy programmes solve the need for morepharmacists?] Plexus 2001;33(5):14-15.

Munck J. Danmarks Farmaceutiske Højskole er udnævnt til MarieCurie Training Site. [Royal Danish School of Pharmacy appointed aMarie Curie Training Site.] Plexus 2001;33(5):21.

Munck J. FKL. Levedygtigt center har passeret de første to år. [Viablecentre survives first two years.] Plexus 2001;33(5):32.

Munck J. Ministermøder med undervisningsminister MargretheVestager. [Meeting Margrethe Vestager, Minister of Education.] Plexus2001;33(5):33-36.

Munck J. De nye farmaceutstuderende. Ansættelse i det offentligevirker ikke tillokkende. [New pharmacy students: public sector jobs notfirst priority.] Plexus 2001;33(6):16-17.

Munck J. Højskolens nye hjemmeside. [New website for Royal DanishSchool of Pharmacy.] Plexus 2001;33(6):28-30.

Munck J, Fjalland I. Integration af fremmedsprogede studerende påde længerevarende videregående uddannelser. [Integration of non-na-tive Danish speakers into higher education programmes.] Plexus2001;33(6):22-23.

Munck J, Vester-Andersen L. DFHs informationsaktiviteter over forpotentielle studere. [Royal Danish School of Pharmacy’s informationinitiatives for potential students.] Plexus 2001;33(6):18-20.

Nørhede A. Er du tilfreds med biblioteket? [Are you satisfied with thelibrary?] Plexus 2000;32(6):21.

Nørhede A. Gratis adgang til patentdatabasen Derwent InnovationsIndex, DII. [Free access to patents. Derwent Innovations Index, DII isopen.] Plexus 2001;33(1):22.

Nørhede A. Elektroniske tidsskrifter bliver brugt.[Electronic journals areused.] Plexus 2001;33(1):12-13.

Nørhede A. Tilfreds med biblioteket? [Satisfied with the library?]Plexus 2001;33(2):20-21.

Nørhede A. Slut med trykte tidsskrifter? [Final curtain for hard-copyjournals?] Plexus 2001;33(3):15-16.

Nørhede A. Slut med katalogkort på Danmarks FarmaceutiskeBibliotek. [Card catalogue discontinued at the Danish PharmaceuticalLibrary.] Plexus 2001;33(4):36.

Nørhede A. Derfor mangler Danmarks Farmaceutiske Bibliotekpenge... [That’s why the Danish Pharmaceutical Library is short ofmoney…] Plexus 2001;33(4):24,26.

Nørhede A. Viden skal deles. Officiel åbning af Danmarks ElektroniskeForskningsbibliotek. [Knowledge must be shared. Official opening ofThe Danish Electronic Research Library.] Plexus 2001;33(5):4-5.

Nørhede A. Mere biblioteksservice til stud.pharm’erne. [More libraryservice for students at the Royal Danish School of Pharmacy.] Plexus2001;33(6):37.

Nørhede A. Brug biblioteket – find informationen! Kompendium.Biblioteksvejledning. Informationssøgning i trykte og elektroniske medi-er. Ny udg. Danmarks Farmaceutiske Bibliotek; 2001. [Use the library– find information!]http://www.dfh.dk/bibliotek/docs/BrugBiblioteket2001.pdf

Nørhede A, Steffensen R, Byrialsen L, Dahlstrøm-Nielsen P.Brugertilfredshed i de elektroniske biblioteker [User satisfaction in elec-tronic libraries].

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Master’s Theses


Allan C. Beck. Water-soluble prodrug derivatives of tertiary amines.Supervisors: Claus Selch Larsen and Karin Fredholt (H. Lundbeck A/S,Copenhagen).

Rikke Brønnum. Investigation of the influence of pesticides on thedentrification rate in wetlands. Supervisor: Sven Erik Jørgensen.

Anne Greve, Gitte Albæk Christensen. Udvikling af analysemetode tilbestemmelse af heroinmetabolitter i fuldblod (Development of anAnalytical Method for the Determination of Heroine Metabolites inWhole Blood). Supervisor: Erling Sonnich Thomsen.

Caroline Marie Hasted. Carbonate esters possessing fatty acid likestructures as model prodrug derivatives of phenol. Supervisors: JesperØstergaard and Claus Selch Larsen.

Mille Holst-Jørgensen. Risikovurdering af parabener i injek-tionsvæsker (Risk Assessment of Parabens in Injection Fluids).Supervisor: Erling Sonnich Thomsen.

Nakisa Jaleshgar. Determination of selenomethionine in tablets byGC-MS. Supervisor: Ole Jøns.

Lars Lundager Madsen. The use of ultrasonic nebulization in induc-tively coupled plasma mass spectrometry for the determination oforganohalogens. Supervisor: Bente Gammelgaard.

Lise Johanna Laurbjerg Nielsen. Effect of fatty acid chain length ofpoly(ethylene oxide)- block-poly(hexylaspartamide amino acid) micelleson the encapsulation and aggregation state of amphotericin B.Supervisors: Claus Selch Larsen and Glen S. Kwon (University ofWisconsin, Madison, USA).

Karen Marie Olesen, Jeanette Reschka. Analyse af benzylpenicillinog dets nedbrydningsprodukter ved anvendelse af HPLC og CE.Udvikling af metoder og nedbrydningsforsøg. Supervisor: JetteTjørnelund.

Rikke Engelbrecht Pedersen. Bionedbrydning af chlorphenoler medefterfølgende formulering af QSAR-modeller. Supervisors: FlemmingIngerslev and Sven Erik Jørgensen.

Henrik Quaade. Solubility of salts of p-substituted benzoic acids andN-methyl and N,N-dimethylbenzylamine- effect of para substituent onsolubility. Supervisors: Henrik Parshad and Claus Selch Larsen.

Peter Rasmussen, Morten Riis. Helicobacter pylori invasion of ep-ithelial cells mediated by proteins in fetal calf serum - protein bindingand invasion studies. Supervisors: Karen Krogsfelt, Statens SerumInstitut and Claus Selch Larsen.

Christian Skonberg. Evaluering af en Tamoxifen “Molecular ImprintedPolymer” til brug ved fastfase-ekstration, herunder udvikling af et

HPLC-system. Udvikling og validering af en HPLC-metode til kvantita-tiv bestemmelse af nogle substituerede benzoesyrer og deresglycinkonjugater til brug ved studier af kvantitative struktur-metabolisme forhold. Supervisor: Steen Honoré Hansen.

Sara Zarei. Ion-pair chromatography in selenium speciation.Supervisor: Ole Jøns.


Maria Bugge. Natriumafhængige højaffinitets glutamat transportører.[Sodiumdependent high-affinity glutamate transporters].Supervisor: Hans Bräuner-Osborne.

Pernille Chantal Canci. Parabener – et strukturstudie. [Parabenes – astructural study]. Supervisor: Karla Frydenvang.

Heidi Eller, Lea Maria Rønneberg. Isolering, identifikation og in vitroantimalaria screening af stoffer fra Soymida febrifuga. [Isolation, identi-fication and in vitro antimalarial screening of compounds from Soymidafebrifuga]. Supervisor: Ulla Wagner Smitt, Jerzy Jaroszewski.

Johan Faber, Petur Weihe Dalsgaard. Isolering og strukturopklaringaf malariaaktive naphthylisoquinolinalkaloider fra Ancistrocladus tan-zanienssis. [Antiplasmodial naphtylisoquinoline alkaloids fromAncitstrocladus tanzaniensis, isolation and structural elucidation].Supervisors: S. Brøgger Christensen, Per Mølgaard.

Christina Høy Fischer. Farmakologisk karakterisering af en rækkeligander for GABAA –receptorer. [Pharmacological characterization ofligands for GABAA-receptors]. Supervisor: Tine Bryan Stensbøl.

Christine Gunnergaard. Kinesiske lægeplanter som antioxidanter.[Chinese herbal drugs containing antioxidants]. Supervisor: SørenBrøgger Christensen.

Kasper Harpsøe, Marie-Louise West Haagensen. Evaluering afMultiSelect og MultiScore. En evaluering af nye procedurer for forud-sigelse af bindingskonformation og bindingsaffinitet. [Evaluation ofMultiSelect and MultiScore. An evaluation of new procedures forpredicting binding conformation and binding affinity]. Supervisor:Flemming Steen Jørgensen.

Birgitte Søndergård Hertz. Syntese af glycin analoger ud fra 1-hy-droxypyrazol. [Synthesis of glycin analogues from 1-hydroxypyrazole].Supervisor: Mikael Begtrup.

Susanne Ellen Høgh. Resolvering, konfigurationsbestemmelse ogenantiofarmakologi af (RS)-2-amino-2-(3-hydroxy-5-phenyl-4-isoxa-zolyl)eddikesyre [(RS)-phenyl-AMAA]. [Resolution, configurational as-signment and enantiopharmacology of (RS)-2-amino-2-(3-hydroxy-5-phenyl-4-isoxazolyl)acetic acid [(RS)-phenyl-AMAA]]. Supervisors: TineB. Stensbøl, Tommy N. Johansen.


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Søren Johnsen. Sæsonvariation af cichoriesyre og alkylamider iEchinacea purpurea. [Seasonal variation in the content of cichoric acidand alkamides from Echinacea purpurea]. Supervisor: Per Mølgaard.

Anette Lauritzen, Iben Skovgaard Lund. Æterisk olie i kantlyng,Cassiope tetragona. - Individuel og geografisk variation samt biologiskaktivitet af indholdsstoffer. [Essential oil in Cassiope tetragona. –Individual and geographical variation, biological activity of con-stituents]. Supervisors: Per Mølgaard, Anne Adsersen.

Jeannette Lauritzen, Lene Jørgensen. Etnofarmakologisk under-søgelse af 21 chilenske lægeplanter. [Ethnopharmacological screeningof 21 medicinal plants]. Supervisors: Per Mølgaard, Anne Adsersen.

Anne Kruse Lykkeberg. Cytotoksiske stoffer i lægemiddelplantenCynanchum vincetoxicum: isolering, strukturopklaring og farmakolo-gisk karakterisering af phenanthroindolizidin-alkaloider. [Cytotoxic com-pounds from the medicinal plant Cynanchum vincetoxicum: isolation,structural elucidation and pharmacological evaluation of phenanthroin-dolizidine alkaloids]. Supervisor: Dan Stærk.

Alma Mustafic, Dea Marie Melskens. Syntese af potentielle GABAAreceptor ligander. [Synthesis of GABAA receptor ligands]. Supervisor:Bente Frølund.

Mette Vorup Møller, Lars Filtenborg Kirk. Videreudvikling af in vitroassay til undersøgelse af stoffers antimalariske aktivitet. [Developmentof assay for assessment of antimalarial activity in vitro]. Supervisors:Jette Christensen, Jerzy W. Jaroszewski.

Tram Bich Thi Nguyen, Trang Ngoc Thi Tran. Undersøgelse af an-timikrobiel aktivitet i vietnamesiske lægeplanter. [Investigations of antimicrobial activities of medicinal plants from Vietnam]. Supervisors: UlfNyman, Ulla Wagner Smitt.

Anne Sophie Toftlund Nielsen, Lone Munch Ringgaard.Glutamatreceptorligander. Stereoselektiv syntese. [Glutamate receptorligands. Stereoselective synthesis]. Supervisors: Lotte Brehm, RasmusPrætorius Clausen.

Kim B. Poulsen. Design og syntese af 4-alkyl-homoibotensyreanaloger. [Design and synthesis of 4-alkyl-homoibotenic acid ana-logues]. Supervisor: Ulf Madsen.

Miquel Poulsen. Konstruktion og karakterisering af et randomiseretmutagent bibliotek af den calcium sensende receptor. [Constructionand characterization of a random saturation mutagenesis library in thecalcium sensing receptor]. Supervisor: Hans Bräuner-Osborne.

Malene Anderberg Radin. Hyben – et potentielt naturlægemiddelmod gigt. [Rose hip – a potential herbal medicine for the treatment ofrheumatism]. Supervisor: Lene Gudiksen.

Maria Alexandra Schrøder. Vin og hjerte-karsygdomme. [Wine andcardiovascular diseases]. Supervisor: Lene Gudiksen.

Keld Agerbæk Siiger. Fremstilling af (R/S) 2-amino-3-(1-hydroxypyra-zol-5-yl) propan syre. [Synthesis of (R/S) 2-amino-3-(1-hydroxypyrazol-5-yl) propane acid]. Supervisor: Mikael Begtrup.

Brian Skole. Isolering og strukturopklaring af potentielle malariaaktiveindholdsstoffer i Landolphia dulcis. [Isolation and structure elucidationof potential antimalarial constituents from Landolphia dulcis].Supervisors: Jerzy W. Jaroszewski, Dan Stærk.

Mehrnoush Tabatabai, Mahboubeh Dadkah Tehrani. Isolering ogstrukturopklaring af stoffer med in vitro antimalaria virkning fra Iranskeplanter. [Isolation and structure elucidation of compounds with in vitroantimalarial activity from Iranian plants]. Supervisor: Jerzy W.Jaroszewski.

Johanna Thulin, Line Thygesen. Antioxidativ effect of Echinacea pur-purea. [Antioxidative effect of Echinacea purpurea]. Supervisors: PerMølgaard, Leif Skibsted, Alan Mortensen.

Hanh Trung Ung, Han Ung. Antioxidativ aktivitet af hyben fraHunderose, Rosa canina L. og Rynket rose, R. rugosa Thunb. og iso-lering af stoffer med antioxidativ effekt. [Antioxidative activity of hipsfrom Rosa canina L. and R. rugosa Thunb. and isolation of antioxida-tive constituents]. Supervisors: Anne Adsersen, Ulla Wagner Smitt.

Petrine Wellendorph. Syntese og farmakologisk karakterisering afphilanthotoxiner og af potentielle calcium-receptor antagonister.[Synthesis and pharmacological characterization of philanthotoxins andpotential calcium-sensing receptor antagonists]. Supervisors: Jerzy W.Jaroszewski, Henrik Franzyk, Hans Bräuner-Osborne.

Erik Zobel. Nye ligander baseret på 1-hydroxypyrazol til stereoselektivsyntese. [New ligands for stereoselective synthesis based on 1-hydroxypyrazoleI]. Supervisor: Mikael Begtrup.


Zahra Abassi, Nahid Abbasi: General principles of quality assuranceof pharmaceuticals and screening tests of tuberculosis and antimalariadrugs. Supervisors: Sabine Koppf-Kubel, WHO Geneva and H. G.Kristensen.

Anette Kildegaard Andersen, Lene Ejstrup Andersen: Monitoringblood flow in AV-fistulas. – Implementing and quality assurance of theUltrasound Dilution Method as a routine method for diagnosing steno-sis in AV-fistulas. Supervisors: Søren Ladefoged, H:S Rigshospitaletand Mette Rasmussen.

Rikke Andersen, Lisbeth Hjorth Nielsen: Evaluation of the transportacross the blood-brain barrier of cyclic prodrugs of an opiod peptideanalog using an in situ rat brain perfusion model. Supervisors: RonaldT. Borchardt, University of Kansas, USA and Bente Steffansen.

Charlotte Arp, Pernille Meldal: Transfer of medication lists – qualityassurance of procedures. Supervisors: Steffen Ulrik Friis, HelsingørHospital and Mette Rasmussen.

Peter Baade: Evaluation of the efficiency of different fluidisation coat-ing equipment at various humidities. Supervisors: Jørn Møller-Sonnergaard, Per Holm, H. Lundbeck A/S.

Tenna Bekker, Helle Houlberg Carlsen: Empirical Prophylaxis ofPost-operative Vomiting versus Structures Prophylaxis.Supervisors: Greg Roberts, Repatriation General Hospital, Adelaide,Australia and Mette Rasmussen.

Sune Bergstrøm: Granulation in different high-shear mixers.Supervisors: Dr. B. Rotthäuser, Aventis Pharma GmbH and H. G.Kristensen.

Mette Line Bergendorff: Preparation and characterisation of inulinencapsulated liposomes for buccal delivery: in vitro study of interactionbetween liposomes and methyl-�-cyclodextrin. Supervisors: CharlotteVermehren, Elias Fattal and Amèlie Bochot (Faculté de Pharmacie,Université Paris-Sud, France).

Charlotte Born: Stability of allergic extracts from Phleum pratenseand Dermatophagoides pteronyssinus in simulated salivary, simulatedgastric fluid and simulated intestinal fluid. Supervisors: Lise Lund ALKAbello and Bente Steffansen.

Bettina Bruun: Polymeric delivery of camptothecin analogs and rabbitcarboxylesterase. Supervisors: Camilla Foged and Birger Brodin.

Anders Christensen: Metabolism of Oxycodone in female SpragueDawley and Female Dark Agouti rat liver microsomes. Supervisors:Andrew Somogyi, University of Adelaide and Lona Christrup.

Saima Durrani: Adsorption of DNA onto cationic dendrimer labelledpolystyrene nanoparticles for gene delivery applications. Supervisors:Lise Lund and Birger Brodin.

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Kirstine Mindegaard Gommesen: Nutrial Support in Intensive CareUnit Patients. Supervisors: Birgitte Skov, Amtssygehuset i Herlev andLona Christrup.

Mette Grove: Formulation of D-vitamin analogues in Self EmulsifyingDrug Delivery systems and Self Microemulsifying Drug DeliverySystems. Supervisors: Sven Frøkjær, Gitte P. Pedersen, LeoPharmaceutical Products A/S.

Adam Guhle: Manufacturing and characterization of pharmaceuticalsalts of a few model drug compounds. Supervisors: L.-E Briggner,AstraZeneca R&D Lund and H. G. Kristensen.

Tue Hansen: Estimation of segregation in the manufacture of tabletsby direct compression. Supervisors: Per Holm, H. Lundbeck and H. G.Kristensen.

Mikael Hansen: Evaluation of the Effect of Implementation of thePharmacokintic Software MW/PHARM in the Dosing of Lithium.Supervisors: Helle Angelo Bispebjerg Hospital and Lona Christrup.

Mette Krogh Hansen, Stina Westergaard Hansen: DissolutionCharacteristics of Solid Dispersions with Hydroxypropyl Methylcellu-lose Phtalate. Supervisors: David Hayes, F. H. Faulding, Salisbury,Australia and Lona Christrup.

Susanne Hostrup: Liposomes as drug delivery system for acylatedpeptides. Supervisors: Sven Frøkjær, Simon Bjerregaard Jensen, NovoNordisk A/S.

Christina Jensen, Lærke Jacobsen: Comparison of crushingstrength testers. Supervisors: Jørn Møller-Sonnergaard, KennethLokind Novo Nordisk A/S.

Lone Friis Jensen, Mikala Holt-Pedersen: Investigation of peptidetransporter activity in buccal TR146 and intestinal Caco-2 cell culturemodels using glycylsarcosine and valacyclovir as substrates.Supervisors: Bente Steffansen, Carsten Uhd Nielsen and Hanne MørckNielsen.

Louise Moe Jönsson: The process of reformulating the Pentasa sup-pository 1 g. Supervisors: Birgitte Nisssen, Ferring Pharmaceuticals,Henning G. Kristensen.

Jeannet E.R. Kall: N-(2-hydoxypropyl)methacrylamide (HPMA) copoly-mers for targeted delivery of polyamine analogs. Supervisors: CamillaFoged and Birger Brodin.

Jakob Gjelstrup Kristensen: Strategic considerations on implementa-tion of quality-assurance relevant to development of new drugs to aglobal market. Supervisors: Jørn Møller-Sonnergaard, Eva De Bang,Morten Juul Sørensen Novo Nordisk A/S.

Lisbeth Kristensen: Optimisation of Permeability and SolubilityAssessment Systems: Potential Extrapolation of Early Screening Datato BSC Classification. Supervisors: Sven Frøkjær, Susanne Sønderkær,Mitchell Taub, Novo Nordisk A/S.

Jesper Lund Larsen: Stabilizing effects of metal ions on insulin hex-amers studied by differential scanning calorimetry. Supervisors: SvenFrøkjær, Peter Langballe, Novo Nordisk A/S.

BM Larsen, Woll JT. Buksis: A physicochemical in vitro model forblod brain barrier-modelling. 2001. Supervisor: Erik Bechgaard.

Jens Ahlefeldt-Laurvigen: Scaling up of a film coating process in aperforated drum, from laboratory scale to pilot scale. August 2000.Supervisors: Breian Knudsen, Novo Nordisk A/S and Torben Schæfer.

Anne-Mette Lilleøre, Lene Kjær: Preformulation aspect of micronisedsolids. Dry- and wet ball-milling of pharmaceutical solids followed byphysical characterisation focusing on the use of a combined micro-thermal analyser and atomic force microscope. Supervisors: SvenFrøkjær, Lars Erik Briggner and Marianne Svärd, AstraZeneca, Lund.

Lars Lundtorp: The use of subcellular liver fractions to predictmetabolic stability and Michaelis-Menten kinetics for a series of p38MAP kinase inhibitors. Supervisors: Sven Frøkjær, Kim Sonne LeoPharmaceutical Product A/S.

Line Torp Madsen, Lisbet Emmery Jørgensen: Metabolits ofMorphine and Hydromorphone in Patiens in Chronic Haemodialysisand in Chronic Pain Patients with Normal Renal Function. Supervisors:Ryan Hansen, Amtssygehuset i Herlev and Lona Christrup.

Line Madsen: Melt agglomeration in a high shear mixer with additionof molten binder by a nozzle. June 2001. Supervisors: Anette Seo andTorben Schæfer.

Kjersti Meling: Formulation and cosmetic evaluation of Water-in-oilemulsions. Supervisor: Margrethe Rømer Rassing.

Bente Nicolaysen, Sofie Paarup Kirkeby Nielsen: Design of an invitro release model with controlled liquid supply to Conteed F®.Supervisors: Kristina Jensen, Coloplast A/S and Bente Steffansen.

Mette Tholstrup Nielsen, Vibeke Rydlund Nielsen: Registration ofSide-Effects of the Treatment with Opioids. Supervisors: Anders SchouOlesen, Aalborg Sygehus Syd and Lona Christrup.

Thomas Berg Nielsen: Control of the granulation process in laborato-ry and production scale high shear mixers by power consumptionmeasurements. June 2001. Supervisors: Per Holm, H. Lundbeck A/Sand Torben Schæfer.

Anne Flachs Nielsen, Merethe Off: Crystallisation of insulin aspart.Supervisors: Jette Jacobsen and Lise Smith.

Kristian Østergaard Nielsen, Hanne Larsen: Patient-controlled anal-gesia in children. Supervisors: Janne Rømsing and Kjeld Schmiegelow,The State University Hospital.

Kristine Juul Nilsson, Louise Vendelbo Jacobsen: Medicine takingbehaviours in Type 2 diabetics at Walton Diabetes Centre. Supervisors:Dave Thornton, University Hospital Aintree, Liverpool, UK and MetteRasmussen.

Tanna Friis Nönnecke, Susanne Kristensen: Evaluation of MiniMental State Examinations (MMSE’s) as a Screening Tool for CognitiveDysfunction in Patients with Chronic Non-Malignant Pain. Supervisors:Jette Højsted, H:S Rigshospitalet and Lona Christrup.

Michael Norsell: Fast pellet disintegrating with a high drug load. Supervisors: Dr G. Hauch, Aventis Pharma GmbH and H. G.Kristensen.

Charlotte R. Paulsen: A study of the lipids in the TR146 cell culturemodel. Supervisors: Margrethe Rømer Rassing and Charlotte Adrian.

Mikala Holt-Pedersen, Lone Friis Jensen: Investigation of peptidetransporter activity in buccal TR-146 and intestinal Caco-2 cell culturemodels. Supervisors: Hanne Mørck Nielsen, Carsten Uhd Nielsen andBente Steffansen.

MH Olsen, SL Pedersen: Olfactory absorption – Study of flourescinetransport from the nasal cavity to the brain. 2001. Supervisor: ErikBechgaard.

Morten Becker Pedersen, Martin Schultz: Ondansetron: What valuein the new millenium at The Children’s Hospital at Westmead.Supervisors: Gwen Higgins and Judith Longworth, The Children’sHospital at Westmead, Sydney, Australia and Mette Rasmussen.

Martin Søe Rasmussen: Matrix tablets based on low vicous HPMC. Supervisors: Lone Nørgaard, Alpharma Ltd. and H. G. Kristensen.

Baljit Singh: Formulation of cationic dendrimer labelled gold particlesfor adsorption and delivery of plasmid DNA. Supervisors: Lise Lundand Birger Brodin.


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Arne Hagsten Sørensen: Comparison of valaciclovir and Glu(acv)-Sarprodrugs with affinity for hPepT1; stability, affinity and transport.Supervisors: Anne Engelbrecht Thomsen and Bente Steffansen.

Mette Thorvaldsen: Aminoglycoside Therapy at Intensive Care Unitsat Danish Hospitals. Supervisors: Jan Bonde, Amtssygehuset i Herlevand Lona Christrup.

Mette Thun: Liposomal stability against phospholipases – a drug de-livery aspect. Supervisors: Charlotte Vermehren, Harald S. Hansen(Dept. of Pharmacology).

Huong Tran, Maja Nøddekær: Formulation and characterization of ananoemulsion. Supervisor: Hanne Mørck Nielsen.

Signe Walmar, Mette Wulff: Aquous ethyl cellulose coating of granu-late for manufacturing of Penatasa tablets with a specified dissolutionprofile. Supervisors: Jørn Møller-Sonnergaard and Birgitte Nissen,Ferring A/S.

Henrik Ravn Aage: Characterization of moisture content in granuleswith regard to prediction of compaction properties. Supervisors:P.Mohr Olsen and P. Berthelsen, Nycomed Pharma and H. G.Kristensen.


Dorthe Birgitte Andersen: Udvikling af kognitive modeller hos mus irelation til skizofreni. [Development of cognitive models in mice in rela-tion to schizophrenia]. Supervisor: Orla Miller Larsson.

Maria Paabøl Andersen: Effekter af henholdsvis akut og kronisk ad-ministration af antipsykotika på modellen for prepulse inhibering hosrotter. [Effects of chronic versus acute treatment with antipsychoticson the prepulse inhibition model in rats]. Supervisor: Orla MillerLarsson.

Jesper Bendtsen: Ekspression af c-fos hos rotter udsat for varme ogkolde omgivelser samt c-fos´ co-lokalisering med neurotensinrecptorer.[Expression of c-fos in rats during warm and cold environments and c-fos co-localization with neurotensine receptors]. Supervisor: BjarneFjalland.

Signe Farsø Bomholt: Effect of NS1231 in a mouse model of focalcerebral ischaemia. Supervisor: Bjarne Fjalland.

Jeanett Borsdal: Hypothermiske effekter af neurotensin, NT69L ogJMV 449 samt den neuroprotektive effekt af hypothermi forårsaget afJMV 449 ved fokal iskæmi. [Hypothermic effects of neurotensin,NT69L and JMV 449 and the neuroprotective effect of JMV 449 in-duced hypothermia in focal ischaemia]. Supervisor: Bjarne Fjalland.

Than Che, Jamila Tahtah: Stress inducerer NOS - Kvantificering afNOS mængden i rotter efter akut og kronisk stressbehandling. [Stressinduces NOS - Quantification of NOS in cerebral arteries and dura af-ter acute and chronic stress]. Supervisor: Inger Jansen Olesen.

Monika Christensen, Lene Landsgrav: Karakterisering af CGRP re-ceptorer i septale koronar arterier fra rotter. [Characterization of CGRPreceptors in septale coronary arteries from rats]. Supervisor: Niels C.Berg Nyborg.

Jesper Drøgemüller: DNA vaccine mod salmonella typhimurium infek-tion fremstilling samt afprøvning i Lewis rotter. [DNA vaccine againstsalmonella typhimurium infection design and testing in Lewis rats].Supervisors: Peter Thygesen and Erik S. Riise.

Anne Fjeldsted Eriksen, Pernille Saxov: Undersøgelse af Matrem-og Parthenolids virkningsmekanisme i migrænebehandling. [Studies ofthe mechanisms of action of Matrem (feverfew) and Parthenolide in re-lation to prophylatic treatment of migraine]. Supervisors: Per Mølgaardand Inger Jansen Olesen.

Mette Fryland: Immunologisk status ved depression og under antide-pressiv behandling. [Immunological status in Major depression andduring antidepressant treatment]. Supervisor: Bjarke Ebert.

Catrine Haugsted Høyer, Gitte Louise Juhl: Varmeinaktivering af py-rogen aktivitet i Bacillus subtilis endosporer. [Heat inactivation of pyro-genic activity in endospores of Bacillus subtilis]. Supervisors: Erik WindHansen and Lise Moesby.

Fida Issa: Cellulær lokalisering af glukagon-lignende peptid-1 recep-torer. [Cellular localization of glucagon-like peptide-1 receptors].Supervisor: Peter Thygesen.

Mikkel Rostgaard Jensen, Allan Astrup Kah: Kvantificering af Fos-positive neuroner som udtryk for nociception hos grise efter intra-muskulær injektion af viscoleo, sesamolie og frie fedtsyrer.[Quantification of Fos-positive neurones as a marker of nociception inpigs after intramuscular injection of Viscoleo, sesam oil and fattyacids]. Supervisor: Bjarne Fjalland.

Lars Ketilsson: Salbumatol induceret IL-6 udskillelse i pituicytter.[Salbumatol induced IL-6 release from pituicyt]. Supervisor: LiseMoesby.

Anne Louise Kirkegaard, Ditte Maria Karpf: Effect of ketoprofen andits enantiomers on the renal disposition of methotrexate in the isolatedperfused rat kidney. Supervisor: Bjarne Fjalland.

Rikke Larsen, Nina Bornhøft Nielsen: CGRP´s involvering i morfintolerance - in vitro forsøg med isolerede organer og neuroner.[Involvement of CGRP in tolerance to morphine - in vitro experimentswith isolated organs and neurones]. Supervisor: Bjarne Fjalland.

Annette Skovgaard Lund, Henrik Kjer Petersen: Gentamicin - do-sisjustering og farmakokinetik hos intensivpatienter. [Gentamicin -Therapeutic drug monitoring and Pharmacokinetics in critically ill pa-tients]. Supervisors: Mette Rasmussen and Søren Rasmussen.

Rikke Marie Lund: Screening for adjuvant effekt af diphthalater imurin injektionsmodel. [Screening for adjuvant effect of diphthalates ina murine injection model]. Supervisor: Peter Thygesen.

Jesper Mosolff Mathiesen: G-protein kobling af den humane neu-rokinin-2 receptor. [G-protein coupling aspects of the human neu-rokinin-2 receptor]. Supervisor: Arne Schousboe.

Christina Nielsen: Aktivering af Mono Mac 6 celler med lipopolysac-charid og lipoteichoinsyre. [Activation of Mono Mac 6 cells withlipopolysaccharide and lipoteichoin acid]. Supervisor: Lise Moesby.

Charlotte Ullitz Olesen, Tina Olesen: Elektrofysiologisk studie afGABAA receptoren. [Electrophysiological investigation of the GABAAreceptor]. Supervisor: Uffe Kristiansen.

Annemette Due Pedersen: LPS-induceret nitrogenoxid produktion idyrkede cellekulturer fra murine neurohypofyser. [LPS-induced releaseof nitrogenoxide by cultured cells from the murine neurohypophysis].Supervisor: Erik Wind Hansen.

Mikkel Pind: Identifikation af protein-protein interaktioner mellemGABAA receptor �4-subunit intracellulært domæne og et eller flere in-tracellulære proteiner ved brug af gærcelle-2-hybridsystemet. [Findingprotein-protein interactions between the �4-subunit intracellular loop ofthe GABAA receptor and one or several intracellular proteins affectingthe �4-subunit, using the yeast two-hybrid system]. Supervisor: ArneSchousboe.

Lone Rahbek, Camilla Recke: Funktionen af serum amyloid P kom-ponent hos patienter med systemisk lupus erythematosus. [Functionof serum amyloid P component in-patients with systemic lupus erythe-matosus]. Supervisor: Peter Thygesen.

Alan Sarup: Differential regulation of the expression of the glutamatetransporters GLT-1 and GLAST by soluble factors in cultures of astro-cytes and organotypic hippocampal slice cultures. Supervisor: ArneSchousboe.

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Christoffer von Sehested Schousboe: Synergistisk effekt mellemopioide- og cannabinoide receptorer i muse vas deferens. [Synergismbetween opioid- and cannabinoide receptors in the mouse vas defer-ens]. Supervisor: Bjarne Fjalland.

Anja Hviid Simonsen: Biokemiske markører i præklinisk forskning.udvikling af et enzym linked immunosorbent assay til måling af type IVcollagen i urin. [Biochemical markers in preclinical research develop-ment of an enzyme linked immunsorbent assay measuring type IV col-lagen fragments in urine]. Supervisor: Erik Wind Hansen.

Caja Skettrup: Modellering af farmakokinetiske parametre for stoffetNN703 i programmerne WinNonLin og NONMEM. [Modelling of phar-macokinetic parameters of NN703 in WinNonLin and NONMEM].Supervisor: Peter Thygesen.

Kristin Skogstrand: Serum amyloid P komponent hos patienter medsystemisk lupus erythematosus. [Serum amyloid P component in-patients with systemic lupus erythematosus]. Supervisor: PeterThygesen.

Ine Blankenberg Skotteheim, Tine Nystrup Stolpe: Studier vedrør-ende ekspression og funktion af UCP3. [Studies on the expressionand function of UCP3]. Supervisor: Arne Schousboe.

Anders Søhoel: Effects of CNS active drugs in animal models forlearning and memory. Supervisor: Bjarne Fjalland.

Helle Møller Sørensen, Annika Weber Rasmussen: Vurdering afsammenhængen mellem erythropoientin-resistent og TT-virus hos hæ-modialysepatienter. [Evaluation of the coherence between erythropoi-entin-resitance and TT-virus in hemodialysis patients]. Supervisors:Mette Rasmussen and Søren Rasmussen.

Peter Sørensen: Fremstilling af rekombinante antistof-reagenser medrelevans for patogenesen af dissemineret sklerose. [Generation of re-combinant antibodies of relevence for the pathogenesis of multiplesclerosis]. Supervisor: Jan Engberg.

Ann Kristina Thomsen, Kamilla Rolsted: Protonaktiverende Na+-kanaler og AMPA-receptorers betydning for degeneration af corticaleneuroner. [The role of proton activated Na+-channels and AMPA recp-tors in degeneration of cortical neurones]. Supervisor: Orla MillerLarsson.

Jeppe Voss: Rotarod studies of benzodiazepine/GABAA receptor ago-nists. Supervisor: Bjarne Fjalland.


Janne Hjorth Henriksen: Danskernes brug af naturlægemidler – ogrelationer til helbred, sundheds- og sygdomsadfærd, uddannelse ogindkomst. [Use of herbal medicine within the Danish population – andrelations to health, health and illness behaviour, education and in-come]. Supervisor: Ebba Holme Hansen.

Karen Hoebeke, Christian Huyghe (Belgian SOCRATES students):Qualitative and quantitative analysis of the asthma therapeutic out-comes monitoring (TOM) projects held in Belgium and Denmark. Danish supervisor: Ellen Westh Sørensen. Belgian supervisor: Prof. Dr.Apr. Sophie Sarre (Vrije Universiteit Brussel).

Mette Faber Jensen: Indlægssedler – præparatrelateret og bruger-orienteret lægemiddelinformation. En sammenlignende analyse af ind-lægssedler i udvalgte EU-lande. [Patient information leaflets. Productrelated and user orientated drug information. A comparative analysis ofpatient information leaflets from selected EU-countries]. Supervisor:Poul R. Kruse.

Asger Svend Johansen: Danskernes holdninger til e-medicin.[Attitudes towards e-medicine within the Danish population – a so-ciodemographic profile]. Supervisor: Ebba Holme Hansen.

Pernille Larsen: Forsyningen af tuberkuloselægemidler i Nepal. [Thesupply of tuberculosis drugs in Nepal]. Supervisor: Ebba HolmeHansen.

Mikkel Nørreslet: ”De nye forbrugere” – Findes på apoteket! [The newconsumers” – Exist at the pharmacy!]. Supervisor: Janine MorgallTraulsen.

Majken Nørskov Petersen: Udbredelsen af “rationel farmakoterapi”på danske apoteker med hensyn til håndkøbslægemidler. [Diffusion of“rational pharmacotherapy” on Danish community pharmacies in re-gard to non-prescription drugs]. Supervisor: Lotte Stig Haugbølle.

Bertel Rüdinger: Fra elfenbenstårn til økonomisk faktor – De danskeuniversiteter under globaliseringen. [From the ivory tower to an eco-nomic factor – Danish universities in the light of globalisation]. Super-visor: Janine Morgall Traulsen.


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MASTER’S THESES

PAGE 125


Staff

THE ROYAL DANISH SCHOOL OF PHARMACY


DK-2100 Copenhagen

Phone: +45 35 30 60 00

Fax: +45 35 30 60 01



(E-mail: initials followed by @dfh.dk)

HEADS OF SCHOOL

Rector

Povl Krogsgaard-Larsen (rektor) Professor, DSc (pharm.) professor, dr.pharm.

Deputy Rector

Bjarne Fjalland (bf) Associate Professor, PhD (pharm.) lektor, ph.d. (pharm.)

MANAGEMENT

Administrator

Judith Christiansen (jc) MA cand.mag.

Head of Personnel Division

Elisabeth Riis (elri) MA (law) cand.jur.

Head of Study Division

Ilse Fjalland (if) MSc (pharm.) cand.pharm.

Head of the Study Board

Jette Jacobsen (jeja) Associate Professor, MSc (pharm.) lektor, cand.pharm.

Head of the Budgeting and Accounting Division

Villy Dahl Jensen (vdj) MA cand.scient.pol.

Head of the Information Office

Jesper Munck (jemu) MA cand.mag.

Head of Library Services

Alice Nørhede (aln) Librarian DB1 bibliotekar DB1

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Departmental Board 2001

Head of Department: Professor Steen Honoré Hansen

Deputy Head of Department: Associate Professor Bent Halling-Sørensen

Professor Claus Selch Larsen

Laboratory Porter Court Schwerdfeger

Associate Professor Claus Cornett

PhD student Anne K. Lykkeberg (observer)

Student Jesper R. Bojsen

Secretariat

Helle Sigetty Bøje +45 35 30 62 61

Inge Miller +45 35 30 62 75

Søren Kragh +45 35 30 64 62

Fax: +45 35 30 60 10

Scientific Staff

Email: Initials followed by @dfh.dk

Andersen, Henrik Rasmus (hra) PhD student, MSc ph.d.-studerende, cand.scient.

Bendahl, Lars (labe) PhD student, MSc ph.d.-studerende, cand.scient.

Brix, Rikke (ribr) PhD student, MSc ph.d.-studerende, cand.scient.

Brøndsted, Helle (hb) Associate Professor, PhD (pharm.) lektor, ph.d. (pharm.)

Cornett, Claus (cc) Associate Professor, PhD (pharm.) lektor, ph.d. (pharm.)

Eberth, Kirsten (ke) Associate Professor, PhD (pharm.) lektor, ph.d. (pharm.)

Farver, Ole (of) Professor, DSc professor, dr.scient.

Gammelgaard, Bente (bg) Associate Professor, PhD (pharm.) lektor, ph.d. (pharm.)

Hagen, Nina (nh) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.

Halling-Sørensen, Bent (bhs) Associate Professor, PhD (pharm.) lektor, ph.d. (pharm.)

Hansen, Steen Honoré (shh) Professor, DSc (pharm.) professor, dr.pharm.

Ingerslev, Flemming (fi) Assistant Professor, Msc (pharm.) adjunkt, ph.d., cand.polyt.

Jacobsen, Anne-Marie (amja) Research Assistant forskningsassistent

Jensen, Berit Packert (bpj) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.

Johannessen, Jane K. (jkj) Assistant Professor, Msc (pharm.) adjunkt, cand.pharm.

Jøns, Ole (oj) Associate Professor, PhD (pharm.) lektor, ph.d. (pharm.)

Jørgensen, Sven Erik (sej) Associate Professor, Dsc docent, dr.scient.

Kristensen, Mads Gjelstrup (mgk) Assistant Professor, Msc (eng.) amanuensis, cand.polyt.

Larsen, Claus Selch (csl) Professor, DSc (pharm.) professor, dr.pharm.

Larsen, Susan Weng (swe) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.

Loke, Marie-Louise (mlc) PhD student, MSc ph.d.-studerende, cand.scient.

Lykkeberg, Anne Kruse (ak) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.

Nielsen, Anders Bach (abn) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.

Nielsen, Søren Nors (snn) Associate Professor, PhD lektor, ph.d. (scient.)

Olesen, Karen-Marie (kmo) University Instructor amanuensis

Olesen, Mogens Nørgaard External Associate Professor, MSc ekstern lektor, cand.scient.

Olsen, Jørgen (jo) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.

Parshad, Henrik (hpa) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.

Sidenius, Ulrik (ulsi) Assistant Professor, MSc adjunkt, cand.scient.

Skonberg, Christian (cs) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.

Steinicke, Ann-Louise (alsl) Research Assistant forskningsassistent

PAGE 127

STAFF


Head of Department: Professor Steen Honoré Hansen

Deputy Head of Department: Associate Professor Bent Halling-Sørensen

Associate Professor Bente Gammelgaard

Senior Laboratory Technician Tove Eckhardt

PhD student Anne K. Lykkeberg (observer)

Student Rune Gildsig

Thomsen, Erling Sonnich (est) Associate Professor, PhD (pharm.) lektor, ph.d. (pharm.)

Zhang, Jingjie (jz) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.

Østergaard, Jesper (joe) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.

Teaching Assistants

Gerd Askaa, Hans Bjerge, Jens Corfitzen, Frank Hansen, Poul Einer Hansen, Henning Brandt Jensen, Inger Spangsberg Jensen, Niels Rhod

Larsen, Mette Sandby Holkenfeldt, Kirsten Rald, Jeanette Reschka

Administative and technical staff

Andersen, Kirsten (ka) Senior Laboratory Technician laboratorieoverassistent

Bech, Lioubov (lib) Trainee, Laboratory Technician laborantpraktikant

Bøje, Helle Sigetty (hsb) Head of Section kontorfuldmægtig, cand.negot.

Eckhardt, Tove (te) Senior Laboratory Technician laboratoriefuldmægtig

Hansen, Karen Margrethe (kmh) Senior Laboratory Technician laboratoriefuldmægtig

Hansen, Torben Lindholm (tlh) Assistant Engineer, Tool Maker ingeniørassistent, værktøjsmager

Hermansen, Susanne (suhe) Senior Laboratory Technician laboratorieoverassistent

Jabin. Suraya (sj) Laboratory Technician laborant

Jochimsen, Lars Halldor (lhj) Electrical Engineer elektronikmekaniker

Kongsbach, Anette Due (adk) Senior Laboratory Technician laboratorieoverassistent

Konstantinovitsch, Carina (cacon) Trainee, Laboratory Technician laborantpraktikant

Kragh, Søren (skr) Clerk kontorassistent

Larsen, Bente (bela) Laboratory Technician laborant

Larsen, Ninna Kjær Cleaner rengøringsassistent

Laursen, Anni Bonde (abl) Cleaner rengøringsassistent

Lind, Nina Cleaner rengøringsassistent

Lunow, Elzbieta (ellu) Laboratory Technician laborant

Miller, Inge (im) Senior Clerk overassistent, ED

Milosevic, Melita Cleaner rengøringsassistent

Schwerdfeger, Court (csc) Laboratory Porter laboratoriemester

Vejlemand, Nina Støber (nsv) Laboratory Engineer laboratorietekniker



Head of Department: Associate Professor Ulf Madsen

Deputy Head of Department: Associate Professor Søren Brøgger Christensen

Associate Professor Flemming Steen Jørgensen

Associate Professor Per Mølgaard

Professor Mikael Begtrup

Cleaner Merete Axkær (observer)

Senior Laboratory Technician Bente Gauguin

Assistant Engineer, Precision Mechanic Karsten Klint

PhD student Hanne Ziegler (observer)

Student Behzad Ghorbani

Secretariat

Main floor:

Anne Lisbeth Frederiksen +45 35 30 62 51

Anne M. Lund +45 35 30 62 91

Fax: +45 35 30 60 41

PAGE 128



Head of Department: Professor Jerzy Jaroszewski

Associate Professor Jette S. Kastrup

Deputy Head of Department: Associate Professor Ulf Madsen

Senior Laboratory Technician Bente Gauguin

Assistant Engineer, Precision Mechanic Karsten Klint

Student Thomas Høgh Jensen

First floor:

Anne-Mette Nielsen +45 35 30 62 41

Second floor:

Anne Nordly +45 35 30 65 11

Fax: +45 35 30 60 40

Scientific Staff


Abrahamsen, Bjarke (ba) Scholar student scholarstipendiat, stud.pharm.

Adsersen, Anne (aad) Associate Professor, MSc (pharm.) lektor, cand.pharm.

Akinleminu, Tine T. (titiak) Research Assistant, MSc (pharm.) forskningsassistent, cand.pharm.

Begtrup, Mikael (mb) Professor, PhD (tech.) professor, ph.d. (tech.)

Bräuner-Osborne, Hans (hbo) Professor, PhD (pharm.) professor, ph.d. (pharm.)

Brehm, Lotte (lb) Associate Professor, PhD (pharm.) lektor, ph.d. (pharm.)

Brown, Lea Dalby (ldb) PhD student, MSc ph.d.-studerende, cand.scient.

Bunch, Lennart (lebu) PhD student, MSc ph.d.-studerende, cand.scient.

Buur, Jette Byberg (jbb) School Manager, Associate Research Professor, PhD (pharm.) forsk.skoleleder, forsk.lektor, ph.d. (pharm.)

Cali, Patrizia (paca) PhD student, MSc ph.d.-studerende

Christensen, Søren Brøgger (sbc) Associate Professor, PhD (pharm.) docent, ph.d. (pharm.)

Clausen, Rasmus Prætorius (rpc) Assistant Research Professor, PhD forskningsadjunkt, ph.d (scient.)

Duker-Eshun, George (gedu) PhD student, MSc ph.d.-studerende

Elm, Peter Larsen (pem) Research Assistant, MSc forskningsassistent, cand.scient.

Eskildsen, Jørgen (jes) PhD student, MSc ph.d.-studerende, cand.scient.

Franzyk, Henrik (hf) Associate Professor, PhD lektor, ph.d. (scient.)

Frydenvang, Karla (kf) Associate Research Professor, PhD (pharm.) forskningslektor, ph.d. (pharm.)

Frølund, Bente (bfr) Associate Professor, PhD (pharm.) lektor, ph.d. (pharm.)

Greenwood, Jeremy R. (jgr) Assistant Research Professor, PhD forskningsadjunkt, ph.d. (med.)

Gudiksen, Lene (lg) Associate Professor, MSc (pharm.) lektor, cand.pharm.

Guldbrandt, Mette (mgu) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.

Hansen, Tom Børsen (tbh) PhD student, MSc ph.d.-studerende, cand.scient.

Hermit, Mette B. (mebh) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.

Hertz, Else Birgitte S. University Instructor, MSc (pharm.) amanuensis, cand.pharm.

Hogner, Anders (ah) PhD student, MSc ph.d.-studerende

Jakobsen, Carsten M. (cja) Assistant Research Professor, PhD (pharm.) forskningsadjunkt, ph.d. (pharm.)

Jaroszewski, Jerzy W. (jj) Professor, PhD professor, ph.d. (scient.)

Jensen, Anders A. (aaj) Assistant Research Professor, PhD (pharm.) forskningsadjunkt, ph.d. (pharm.)

Jensen, Birthe (bj) Associate Professor, DSc (pharm.) lektor, dr.pharm.

Jensen, Heidi Dorte (hdj) PhD student, MSc (food chemistry) ph.d.-studerende, cand.tech.al.

Johansen, Tommy Nørskov (tnj) Associate Professor, PhD (pharm.) lektor, ph.d. (pharm.)

Jørgensen, Anne Techau (atj) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.

Jørgensen, Charlotte Grube (chj) Research Assistant, MSc (eng.) forskningsassistent, cand.polyt.

Jørgensen, Flemming Steen (fsj) Associate Professor, PhD docent, ph.d. (scient.)

Jørgensen, Malene Ryborg (mrj) PhD student, MSc (eng.) ph.d.-studerende, cand.polyt.

Kasper, Christina (ck) Assistant Research Professor, MSc, PhD (pharm.) forsk.adjunkt, cand.scient, ph.d. (pharm.)

Kastrup, Jette Sandholm (jsk) Associate Professor, PhD (pharm.) lektor, cand.pharm., erhvervsforsker

Kristensen, Jørgen Bonefeld Scholarstudent scholarstipendiat, stud.pharm.

Krogsgaard-Larsen, Povl (ano) Rector, Professor, DSc (pharm.) rektor, professor, dr.pharm.

Kæseler, Nina Dürr University Instructor, MSc (pharm.) amanuensis, cand.pharm.

Larsen, Ingrid Kjøller (ikl) Associate Professor, PhD (pharm.) lektor, ph.d. (pharm.)

Larsen, Uffe (ul) PhD student, MSc ph.d.-studerende, cand.scient.

PAGE 129

STAFF

Lauritzen, Anette Scholarstudent scholarstipendiat, stud.pharm.

Liljefors, Tommy (tl) Professor, PhD (chemistry) professor, fil.dr.

Lunn, Marie-Louise PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.

Madsen, Christian (chm) PhD student, MSc ph.d.-studerende, cand.scient.

Madsen, Ulf (um) Associate Professor, PhD (pharm.) lektor, ph.d. (pharm.)

Mølgaard, Per (pm) Associate Professor, PhD (agro.) lektor, ph.d. (agro.)

Nielsen, Bettina Bryde (bbn) Assistant Research Professor PhD (pharm.) forskningsadjunkt, ph.d. (pharm.)

Nielsen, Birgitte (bn) Research Assistant, MSc (pharm.) forskningsassistent, cand.pharm.

Nielsen, Mogens (mon) Associate Professor, MSc lektor, cand.scient.

Olsen, Christian Adam (cao) PhD student, MSc (eng.) ph.d.-studerende, cand.polyt.

Olsen, Lotte (lool) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.

Pawlas, Jan (japa) Assistant Professor, PhD (pharm.) adjunkt, ph.d. (pharm.)

Petersen, Dorte Krehan Seir (dsp) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.

Petersson Britt (bp) PhD student MSc (pharm.) ph.d.-studerende, cand.pharm.

Poulsen, Anders (ap) PhD student, MSc (eng.) ph.d.-studerende, cand.polyt.

Rønsted, Nina (nir) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.

Sairafianpour, Majid (msai) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.

Severinsen, Rune (rs) PhD student, MSc ph.d.-studerende, cand.scient.

Simonsen, Henrik Toft (hts) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.

Smitt, Ulla Wagner (uws) Associate Professor, PhD (pharm.) lektor, ph.d. (pharm.)

Strømgaard, Kristian (krst) Assistant Research Professor, PhD (pharm.) forskningsadjunkt, ph.d. (pharm.)

Stærk, Dan (ds) Assistant Professor, MSc, PhD (pharm.) adjunkt, cand.scient., ph.d. (pharm.)

Valgeirsson, Jón (jv) PhD student, MSc ph.d.-studerende

Vogensen, Stine Byskov (sv) PhD student, MSc, (pharm.) ph.d.-studerende, cand.pharm.

Wellendorph Petrine (pw) University Instructor, MSc (pharm.) amanuensis, cand.pharm.

Wenckens, Martin (mwe) PhD student, MSc ph.d.-studerende, cand.scient.

Ziegler, Hanne (hz) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.

Østergaard, Niels PhD student, MSc (eng.) ph.d.-studerende, cand.polyt.

Administrative and technical staff

Allen, Jeanette Cleaner rengøringsassistent

Axkær, Merete Cleaner rengøringsassistent

Brix, Dorte (db) Senior Laboratory Technician laborant, laboratorieoverassistent

Christensen, Peter A. Trainee, Precision Mechanic finmekanikerelev

Christensen, Peter (pc) Laboratory Engineer, Senior Laboratory Technician laboratorietekniker, laboratorieoverassistent

Døring, Heidi L. (hela) Senior Laboratory Technician laborant, laboratorieoverassistent

Eriksen, Anette Lundskov (ale) Senior Laboratory Technician laborant, laboratorieoverassistent

Frederiksen, Anne Lisbeth (alf) Senior Clerk overassistent

Gauguin, Bente (bega) Senior Laboratory Technician laborant, laboratorieoverassistent

Geneser, Ulla (ug) Laboratory Engineer, Senoir Laboratory Technician laboratorietekniker, laboratoriefuldmægtig

Jensen, Kurt Hjælm Cleaner sanitør

Jensen, Frank Stau Trainee, Precision Mechanic finmekanikerelev

Jørgensen, Anders (aj) Web Student Assistant web-studentermedhjælper

Jørgensen, Jan Skov Semi-skilled worker specialarbejder

Keshtkar, Sharareh (shk) Senior Laboratory Technician laborant, laboratorieoverassistent

Klint, Karsten (kk) Assistant Engineer, Precision Mechanic ingeniørassistent, finmekaniker

Krogsgaard-Larsen, Niels Student Assistent studentermedhjælper

Krydsfeldt, Katrine (kakr) Senior Laboratory Technician laborant, laboratorieoverassistent

Lindgreen, Tina (tili) Senior Laboratory Technician laborant, laboratorieoverassistent

Lund, Anne M. Senior Clerk overassistent

Møller, Per Thrane Semi-skilled worker specialarbejder

PAGE 130


Ngamrabiab, Uraiwan (ung) Senior Laboratory Technician laborant, laboratorieoverassistent

Nielsen, Anne-Mette (amn) Managing Clerk kontorfuldmægtig

Nordly, Anne (ano) Managing Clerk kontorfuldmægtig

Palmgren-Salomonsson, Lars (lp) Laboratory Porter, Precision Mechanic laboratoriebetjent, finmekaniker

Rad, Shahroz Tavakoli Cleaner rengøringsassistent

Rasmussen, Peter Student Assistant studentermedhjælper

Rønne, Bente Cleaner rengøringsassistent

Simonsen, Birgitte (bsi) Senior Laboratory Engineer laboratorietekniker, laboratorieoverassistent

Sørensen, Lise Baadsgaard (lbs) Senior Laboratory Engineer laboratorietekniker, laboratorieoverassistent


Deparmental Board 2001

Head of Department: Associate Professor Margrethe Rømer Rassing

Deputy Head of Department: Associate Professor Bente Steffansen

Associate Professor Jørn Møller-Sonnergaard

Assistant Engineer Arne Steinicke Jensen

Student Erik Thygesen

Secretariat

Open from: 8.30 A.M. - 3.00 P.M. +45 35 30 62 36

Fax +45 35 30 60 30, 3rd floor

Fax +45 35 30 60 31, 7th floor

Scientific Staff

Email: Initials followed by @dfh.dk.

Adrian, Charlotte (ca) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.

Bagger, Morten (moba) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.

Bechgaard, Erik (eb) Associate Professor, PhD, MSc (pharm.) lektor, ph.d. (pharm.)

Beier, Anne Mette (aho) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.

Brodin, Birger (bbr) Associate Research Professor, PhD forskningslektor, (lic.scient.)

Christensen, Janne Ørskov (jach) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.

Christrup, Lona Louring (llc) Associate Professor, PhD, MSc (pharm.) lektor, ph.d. (pharm.)

Davidsen, Jesper (jeda) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.

Eriksson, André Huss (ahe) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.

Foged, Camilla (cfo) PhD student, MSc ph.d.-studerende, cand.scient.

Frederiksen, Kjeldtoft Henrik (hkf) PhD student, Msc (pharm.) ph.d.-studerende, cand.pharm.

Frøkjær, Sven (sf) Professor, PhD, MSc (pharm.) professor, ph.d. (pharm.)

Hansen, Tue (tue) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.

Heydenreich, Annette Vinther (ava) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.

Hovgaard, Lars (lh) Associate Professor, PhD, MSc (pharm.) lektor, ph.d. (pharm.)

Høst, Jan (jaho) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.

Jacobsen, Jette (jeja) Associate Professor, PhD, MSc (pharm.) lektor, ph.d. (pharm.)

Johansen, Anita (aj) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.

Jørgensen, Lene (lej) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.

Karpf, Ditte Maria (dmk) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.

Kristensen, Henning Gjelstrup (hgk) Professor, DSc (pharm.) professor, dr.pharm.

Kristensen, Jakob (jk) University Instructor, MSc (pharm.) amanuensis, cand.pharm.

Larsen, Casper Crilles PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.

PAGE 131

STAFF


Head of Department: Associate Professor Lars Hovgaard

Deputy Head of Department: Associate Professor Bente Steffansen

Associate Professor Jørn Møller-Sonnergaard

Assistant Engineer Arne Steinicke Jensen

PhD student Camilla Foged (observer)

Student Jacob Grønne

Lennernäs, Hans Assigned Professor adjungeret professor

Manby, Pedersen Kenneth (kma) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.

Müllertz, Anette (amu) Associate Professor, PhD, MSc lektor, ph.d. (civ.ing.)

Møller, Horn Eva (ehm) Assistant professor, PhD, MSc adjunkt, ph.d.

Møllmann, Hostrup Susanne (shm) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.

Møller-Sonnergaard, Jørn (jms) Associate Professor, PhD, MSc (pharm.) lektor, ph.d. (pharm.)

Nielsen, Carsten Uhd (cun) Assistant professor, MSc (pharm.) adjunkt, cand.pharm.

Nielsen, Hanne Mørck (hmn) Assistant Research Professor, PhD, MSc (pharm.) forskningsadjunkt, ph.d. (pharm.)

Nielsen, Seier Flemming (fsn) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.

Pedersen, Tina Bjeldskov (tbp) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.

Petersen, Frederik Jacob (fjp) University Instructor, MSc (pharm.) amanuensis, ph.d.-stud. cand.pharm.

Petersen, Kamilla Buchberg (kbp) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.

Rasmussen, Mette (mr) Associate Professor, PhD, MSc (pharm.) lektor, ph.d. (pharm.)

Rassing, Margrethe Rømer (mrr) Associate Professor, PhD, MSc (pharm.) lektor, ph.d. (pharm.)

Rømsing, Janne (jr) Associate Professor, PhD, MSc (pharm.) lektor, ph.d. (pharm.)

Schæfer, Torben (ts) Associate Professor, DSc (pharm.) lektor, dr.pharm.

Seo, Anette Elin (aes) PhD student, MSc ph.d.-studerende, m.sc.

Spliid, Henrik ([email protected]) External Associate Professor, PhD (tech.) ekstern lektor, lic.tech.

Steffansen, Bente (bds) Associate Professor, PhD, MSc (pharm.) lektor, ph.d. (pharm.)

Storm, Gert Assigned Professor adjungeret professor

Ståhl, Kristina (krs) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.

Sunesen, Vibeke Hougaard (vhj) PhD student, MSc (eng.) ph.d.-studerende, cand.polyt.

Sønderkær, Susanne (suso) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.

Thomsen, Anne Engelbrecht (anth) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.

Tjellesen, Lone External Associate Professor ekstern lektor, afdelingslæge, dr.med.

Vermehren, Charlotte (cv) Associate Professor, PhD, MSc (pharm.) lektor, ph.d. (pharm.)

Weert,van de Marco (mvdw) Research Fellow forskningsstipendiat, ph.d. (pharm.)

Wørts, Ole ([email protected]) Assigned Professor adjungeret professor, direktør

Administrative and technical staff

Boldsen, Ida (ida) Senior Laboratory Technician laboratorieoverassistent

Christensen, Malene (mc) Trainee, Laboratory Technician laborantpraktikant

Davidsen, Jytte (jd) Pharmaconomist farmakonom

Dinitzen, Bettina (bedi) Senior Laboratory Technician laboratorieleder

Eltong, Birgitte (biel) Senior Laboratory Technician laboratorieoverassistent

Hannestad, Ove (oh) Laboratory Porter laboratoriebetjent

Hansen, Ruth (ruha) Pharmaconomist farmakonom

Jensen, Arne Steinicke (arje) Assistant Engineer ingeniørassistent

Jensen, Nanni (nj) Senior Clerk overassistent

Jespersen, Lotte (lj) Pharmaconomist farmakonom

Johnsen, Dorrit (dj) Senior Laboratory Technician laboratorieoverassistent

Jørgensen, Liv Cleaner rengøringsassistent

Jørgensen, Claus Cleaner rengøringsassistent

Klausen, Irene (irk) Temporary Lab Technician laborantvikar

Lynge, Sussi Cleaner rengøringsassistent

Nicolajsen, Henning Bo (hbn) Head of Secretariat, MSc (econ.) sekretariatsleder, cand.polit.

Nielsen, Erik (erni) Assistant Engineer ingeniørassistent, elektronikmekaniker

Nielsen, Niels Erik (nen) Assistant Engineer, Precision Mechanic ingeniørassistent, finmekaniker

Pedersen, Ellkier Janne (jep) Pharmaconomist farmakonom

Stevner, Lene (les) Pharmaconomist farmakonom

Sørensen, Marja Leena (mls) Senior Clerk overassistent

PAGE 132


Sørensen, Susanne Nørskov (sns) Senior Laboratory Technician laboratorietekniker

Wégens, Birthe (bw) Managing Clerk kontorfuldmægtig

Zhao, Ya Hong Cleaner rengøringsassistent



Head of Department: Associate Professor, Erik Wind Hansen

Deputy Head of Department: Associate Professor Inger Jansen Olesen

Associate Professor: Klaus Bahl Andersen

Senior Laboratory Technician Jytte Palmgren Salomonsson

Senior Laboratory Technician Gunilla Steven

PhD student Henrik Tang Vestergaard (observer)

Student Anne Zimmermann

Secretariat

Ruth Jensen +45 35 30 63 21

Eva Nielsen +45 35 30 63 29

Fax: +45 35 30 60 20

Scientific Staff


Andersen, Klaus Bahl (kba) Associate Professor, PhD lektor, ph.d. (lic.scient.)

Bjerrum, Ole Jannik (ojb) Professor, M.D., D.M. Sci. professor, dr.med.

Christensen, Jens Dencker (jdc) Associate Professor, PhD lektor, ph.d. (lic.pharm.)

Christensen, Lars Harder (lhc) Scholarship Student (pharm.) stud.pharm. scholarstipendiat

Clausen, Rikke (ricl) PhD student, MSc ph.d.-studerende, cand.scient.

Dalsgaard, Grethe Tang (gtd) Research Assistant, MSc (pharm.) forskningsassistent, cand.pharm.

Engberg, Jan (fax: 35 30 60 22) (je) Professor, DSc professor, (dr.scient.)

Erichsen, Helle Kirstein PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.

Fjalland, Bjarne (bf) Associate Professor, PhD lektor, ph.d. (lic.pharm.)

Frandsen, Aase (aaf) Associate Professor, DSc lektor, dr.scient.

Fuglsang, Anders (anfu) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.

Gegelashvili, Georgi (gege) Associate Professor, PhD lektor, ph.d.

Hansen, Erik Wind (ewh) Associate Professor, PhD lektor, ph.d. (lic.pharm.)

Hansen, Harald S. (hsh) Associate Professor, DSc docent, dr.scient.

Hansen, Henrik Assistant Research Professor, MSc (pharm.) forskningsadjunkt, cand.pharm.

Hermansen, Keld Veterinary Advisor veterinært tilsyn

Jelic, Katarina (kaje) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.

Jensen, Liselotte Brix (lbj) PhD student, MSc ph.d.-studerende, cand.scient.

Jensen, Marianne Lerbech PhD student, MSc ph.d.-studerende, cand.scient.

Johansen, Thue PhD student MSc (med.) ph.d.-studerende, cand.med.

Klavsen, Tine (tikl) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.

Kristiansen, Uffe (uk) Associate Professor, PhD lektor, ph.d. (pharm.)

Kristensen, Anders Skov (ask) PhD student, MSc ph.d.-studerende cand.scient.

Kyhl, Lars Erik Broksøe (lek) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.

Larsen, Helmer Ring (hrl) Professor, M.D., D.M. Sci. professor, dr.med.

Larsen, Søren Thor PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.

Larsson, Orla Miller (oml) Associate Professor, PhD lektor, ph.d. (lic.scient.)

Lund, Trine Meldgaard (tml) Associate Professor, PhD lektor, ph.d. (lic.pharm.)

PAGE 133

STAFF


Head of Department: Associate Professor, Erik Wind Hansen

Deputy Head of Department: Associate Professor Inger Jansen Olesen

Professor Arne Schousboe

Senior Laboratory Technician Jytte Palmgren Salomonsson

Laboratory Porter Teddy Pærremand

PhD student Henrik Tang Vestergaard (observer)

Student Marianne Hald Larsen

Moesby, Lise (lm) Associate Professor, PhD lektor, ph.d. (pharm.)

Moesgaard, Birthe (bm) Assistant Professor, MSc adjunkt, (cand.scient.)

Mortensen, Martin (mamo) PhD student, MSc ph.d.-studerende, cand.scient.

Maach-Møller, Bo External Associate Professor ekstern lektor

Nielsen, Pia Birch (piab) PhD student, MSc (pharm.) ph.d.studerende, cand.pharm.

Olesen, Inger (io) Associate Professor, M.D., D.M. Sci. lektor, dr.med.

Petersen, Gitte (gipe) University Instructur, MSc (pharm.) amanuensis, cand.pharm.

Petersen, Karina PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.

Pickering, Darryl (picker) Associate Professor, PhD lektor, ph.d.

Poulsen, Claus Fog (cfp) PhD student, MSc ph.d.-studerende, cand.scient.

Rasmussen, Søren External Associate Professor ekstern lektor

Riise, Erik S. (esr) Associate Professor lektor, ph.d. (scient.)

Sarup, Alan (asa) Research Assistant, MSc (pharm.) forskningsassistent (cand.pharm.)

Schousboe, Arne (fax: 35 30 60 21) (as) Professor, DSc professor, dr.scient.

Sheykhzade, Majid (mash) Assistant Professor, MSc (pharm.) adjunkt, ph.d.

Sveigaard, Helle H. PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.

Thygesen, Peter External Associate Professor ekstern lektor

Vestergaard, Henrik Tang (htv) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.

Waagepetersen, Helle Sønderby (hsw) Assistant Research Professor, PhD forskningsadjunkt

Zedeler, Anne (az) PhD student, MSc ph.d.studerende, cand.scient.

Zinck, Tina (tzi) PhD student, MSc ph.d.studerende, cand.scient.

Teaching Assistants

Jesper Drøgemüller


Bonnichsen, Michael (mibo) Laboratory Porter/keeper laboratoriebetjent/dyrepasser

Busk, Kirsten Aagaard (kab) Senior Laboratory Technician laboratorieoverassistent

Bötkjær, Anja Student Assistant studentermedhjælp

Colding, Janne Møgelhøj (jco) Laboratory Engineer laboratorietekniker

Danø, Hanne (hd) Managing Clerk kontorfuldmægtig

Dyhrfjeld, Helle (hdy) Substitute Laboratory Engineer laboratorieteknikervikar

Hansen, Helle Dupont (hdh) Cleaner rengøringsassistent

Hansen, Ruth (ruh) Cleaner rengøringsassistent

Hedeman, Sanne S. (sahe) Senior Laboratory Technician laboratorieoverassistent

Helbo, Anders (ahelbo) EDP Student Assistant EDB studentermedhjælp

Jensen, Bettina (beje) Laboratory Porter/keeper laboratoriebetjent/dyrepasser

Jensen, Randi (rje) Senior Laboratory Technician laboratorieoverassistent

Jensen, Ruth (rj) Senior Clerk overassistent

Krogsriis, Anne-Mette Laboratory Technician laborant

Lynggaard, Katrine Riis (krl) Cleaner rengøringsassistent

Metz, Kirsten (kme) Senior Laboratory Technician laboratorieoverassistent

Michäely, Marianne (mami) Laboratory Engineer laboratorietekniker

Nielsen, Eva (en) Senior Clerk overassistent

Palmgren, Jytte S. (jps) Senior Laboratory Technician laboratorieoverassistent

Petersen, Lone (lope) Laboratory Engineer laboratorietekniker

Petersen, Rudy (rpe) Cleaner rengøringsassistent

Pærremand, Teddy (tp) Laboratory Porter laboratoriebetjent

Rützou, Cathrine Student Assistant studentermedhjælp

Schøler, Betina (bsc) Laboratory Engineer laboratorietekniker

Steven, Gunilla (gs) Senior Laboratory Technician laboratorieoverassistent

PAGE 134


Strynbo, Marianne (ms) Assistant assistent

Søndergaard, Robert (rsn) Trainee, Laboratory Technician laborantelev

Sørensen, Grete (grs) Senior Laboratory Technician laboratorieoverassistent

Thuesen, Kirsten (kit) Laboratory Engineer laboratorietekniker

Voss, Jeppe Student Assistant studentermedhjælp



Head of Department: Associate Professor Poul R. Kruse

Deputy Head of Department: Professor Ebba Holme Hansen

Associate Professor Janine M. Morgall Traulsen

Managing Clerk Jytte Sørensen

PhD student Kristin Eskildsen (observer)

Student Helle Poulsen

Secretariat

9.00 am - 3.30 pm

Tel.: +45 35 30 63 44 / +45 35 30 63 50 / +45 35 30 62 23

Fax: +45 35 30 60 50

Scientific staff


Christensen, Søren Troels (stc) Assistant Research Professor, PhD (pharm.) forskningsadjunkt, ph.d. (pharm.)

Clausen, Jørgen External Associate Professor, PhD, MSc (econ.) ekstern lektor, ph.d., cand.oecon.

Eskildsen, Kristin (kres) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.

Hansen, Ebba Holme (ehh) Professor, MSc (pharm.) professor, cand.pharm.

Hansen, Kim Haugbølle External Associate Professor, PhD, MSc (eng.), BSc (pol.sc.) ekstern lektor, ph.d., cand.polyt.

Haugbølle, Lotte Stig (lsh) Associate Professor PhD (pharm.) lektor, ph.d. (pharm.)

Hopp, Trine (trh) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.

Jensen, Thomas Clemens, (thcj) University Instructor, MSc (pharm.) amanuensis, cand.pharm.

Karkee, Shiba PhD student, MSc (clin. pharmacol.) ph.d.-studerende, MSc (clin.pharmacol.)

Knudsen, Pia (pini) Assistant Professor PhD (pharm.) adjunkt, ph.d. (pharm.)

Kruse, Poul R. (pk) Associate Professor, DSc (pharm.) lektor, dr.pharm.

Larsen, Jakob Bjerg (jbl) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.

Launsø, Laila (ll) Associate Professor, DSc (sociology) lektor, dr.scient.soc.

Mishra, Pranaya PhD student, MSc (clin.pharmacol.) ph.d.-studerende, M.Sc. (clin.pharmacol.)

Møldrup, Claus (cm) Assistant Research Professor, PhD (pharm.) forskningsadjunkt, ph.d. (pharm.)

Nielsen, Merete W. (mwn) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.

Rossing, Charlotte (chan) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.

Rüdinger, Bertel (br) PhD student, MSc (pharm.) ph.d.-studerende, cand.pharm.

Sørensen, Ellen Westh (ews) Associate Professor, MSc (pharm.) lektor, cand.pharm.

Trap, Birna PhD student, MSc (pharm.), BCom ph.d.-studerende, cand.pharm., HD

Traulsen, Janine M. Morgall (jam) Associate Professor, PhD (sociology) lektor, fil.dr.


Andersen, Gunhild (ga) Clerk, Cleaner kontorassistent, rengøringsassistent

Jensen, Anne Blem (abj) Senior Clerk, Language Secretary overassistent, korrespondent

Nørgaard, Jette (jen) Senior Clerk, Language Secretary overassistent, korrespondent

Sørensen, Jytte (js) Managing Clerk, BCom kontorfuldmægtig, merkonom

PAGE 135

STAFF


On leave: Head of Department: Associate Professor Lotte Stig Haugbølle

Acting Head of Department: Professor Ebba Holme Hansen

Acting Deputy Head of Department: Associate Professor Claus Møldrup

Senior Clerk Anne Blem Jensen

PhD student Kristin Eskildsen (observer)

Student Anders Helbo


THE DANISH PHARMACEUTICAL LIBRARY

Phone: + 45 35 30 63 19

Fax: + 45 35 30 60 60

Opening Hours:

Monday – Thursday: 9 - 16; Friday 10 - 15.30

Check opening hours in July and August

Information:

Circulation desk + 45 35 30 63 19

Information desk + 45 35 30 64 60


Library Board

Alice Nørhede, The Library

Annemette Møller Hansen, The Library

Søren Brøgger Christensen, Department of Medicinal Chemistry

Orla Miller Larsson, Department of Pharmacology

Margrethe Rømer Rassing, Department of Pharmacy

Erling Sonnich Thomsen, Department of Analytical and Pharmaceutical Chemistry

Ellen Westh Sørensen, Department of Social Pharmacy

Henrik Parshad, PhD Department of Pharmacy

Marianne Hald Larsen, student

Anne Zimmermann, student

Staff

E-mail: Initials followed by @dfh.dk

Bladt, Birgitte Ruste (brb) Clerk assistent

Hald, Niels Peter Krogh Student Assistant studentermedhjælp

Hansen, Annemette Møller (amh) Research Librarian, MSc (pharm.) forskningsbibliotekar, cand.pharm.

Keller, Marianne (mk) Librarian bibliotekar

Kaad, Lene (leka) Librarian bibliotekar

Munck, Jesper (jemu) Information Officer, MA informationsmedarbejder, cand.mag.

Nørhede, Alice (aln) Head of Library Service biblioteksleder

Overgaard, Ole (olo) Library Porter biblioteksbetjent

Petersen, Filip Hetmar Cleaner rengøringsassistent

Thiesen, Lis (lt) Senior Clerk overassistent

Weile, Martin (mw) Librarian bibliotekar

PAGE 136

ADMINISTRATION DEPARTMENT

Opening hours:

Monday – Thursday 8.30 - 16; Friday 8.30 - 15.30

Phone: +45 35 30 60 00

Fax: +45 35 30 60 01

E-mail: Initials followed by @dfh.dk

HEADS OF SCHOOL

Rector:

Povl Krogsgaard-Larsen (rektor) Professor, DSc (pharm.) professor, dr.pharm.

Deputy Rector:

Bjarne Fjalland (bf) Associate Professor, PhD (pharm.) lektor, ph.d. (pharm.)

Administrator

Judith Christiansen (jc) MA cand.mag.

Security officer

Johansen, Jørgen Stage (jsj) Laboratory Engineer laboratorietekniker

Personnel department

Almegaard, Tine (ta) Administrative Officer, LLB fuldmægtig, cand.jur.

Gindeberg, Marianne (magi) Senior Clerk overassistent

Hansen, Tina Senn (tsh) Senior Clerk overassistent

Jensen, Anni Kølner (akj) Senior Clerk, Receptionist overassistent, receptionen

Knudsen, Tage Ø. (tk) Head Porter betjentformand

Langhoff, Birgit (bila) Senior Clerk overassistent

Pedersen, Susanne (sp) Senior Clerk overassistent

Riis, Elisabeth (elri) Head of Secretariat, LLB sekretariatschef, cand.jur.

Sørensen, Anne (ans) Senior Clerk overassistent

Tribe, Louise (ltr) Administrative Officer, LLB fuldmægtig, cand.jur.

Course administration

Fjalland, Ilse (if) Registrar, MSc (pharm.) studiechef, cand.pharm.

Flarup, Malene (mf) Office Trainee kontorelev

Jørgensen, Marianne W. (mwj) Administrative Officer, BcomInt fuldmægtig, cand.merc.int.

Laursen, Inge Debois (idl) Administrative Officer, MSc (pharm.) fuldmægtig, cand.pharm.

Ottosen, Susanne (sus) Managing Clerk kontorfuldmægtig

Sjelle, Pia (pia) Senior Clerk overassistent

Ulriksen, Gitte Metz (gmu) Senior Clerk overassistent

Vester-Andersen, Lærke (lva) Administrative Office,r MSc (pharm.) fuldmægtig, cand.pharm.

Wiese, Lone (lw) Senior Clerk overassistent

Course guidance

Dahl, Christoffer (cdl) Student Counsellor, pharmacy student studievejleder, stud.pharm.

Kendra, Jimmy (jik) Student Counsellor, pharmacy student studievejleder, stud.pharm.

Koch, Bettina (beko) Student Counsellor, pharmacy student studievejleder, stud.pharm.

PAGE 137

STAFF

Finance department

Andersen, Dorthe (doan) Senior Clerk overassistent

Bernhard, Rikke (rbj) Senior Clerk overassistent

Christiansen, Anja (ac) Office Trainee kontorelev

Freidal, Manon (mf) Senior Clerk overassistent

Haugan, Britta (bh) Managing Clerk kontorfuldmægtig

Jensen, Ann-Mari Østergaard (amj) Senior Clerk overassistent

Jensen, Villy Dahl (vdj) Finance Manager, BSc (econ.) økonomichef, cand.scient.pol.

Jørgensen, Tina Lund (tlj) Clerk assistent (+ DSR)

Knudsen, Flemming Siggaard (fsk) Managing Clerk fuldmægtig

Higher education administration system (STADS)

Borgholm, Birthe (bb) Electronic Data Consultant, MSc edbkonsulent, cand.scient.

Web

Korzen, Henrik (heko) Webmaster webmaster

IT department

Andersen, Jesper Stemann (jsa) Student Assistant studentermedhjælp

Aunfelt, Karsten (kau) System Administrator systemadministrator

Hossein, Ehsani (hoeh) Electronic Data Assistant, Engineer edb-tekniker, ingeniør

Szymanski, Thomas (tsz) Student Assistant studentermedhjælp

Sørensen, Jørn Bo (jbs) Head of IT IT-leder

Technical services

Christensen, Tom Mechanic maskinarbejder

Olsen, Allan (alol) Mechanic maskinarbejder

Olsen, Freddy Technical Assistant specialarbejder

Petersen, John (jop) Engineer maskinmester

Building administration

Bender, Allan Porter betjent

Harder, Ronald (roha) Porter betjent

Knudsen, Tage Ø. (tk) Head Porter betjentformand, portner

Rasmussen, Kjeld (kjr) Building Administrator bygningsforvalter

PAGE 138


Danmarks Farmaceutiske Højskole


2100 København Ø

Telefon: 35 30 60 00

Fax: 35 30 60 01



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