doping yesterday, today, tomorrow

Doping

Yesterday, Today, Tomorrow

Roberto Verna MD, PhDProfessor of Clinical Pathology and

Director, Clinical Research Center, “Sapienza” University of Rome

President of the Italian Association of Clinical Pathology and

Molecular Medicine

Member of the WASPaLM Bureau

Prof. Roberto Verna

DOPING

Prof. Roberto Verna

WhatWhat isisdoping?doping?doping?doping?

Prof. Roberto Verna

Doping Doping accordingaccording toto the the ItalianItalian LawLawDecemberDecember 14th, 2000, n14th, 2000, n°°376 (art. 1) 376 (art. 1) ofof

the the MinistryMinistry ofof HealthHealth::

“doping “doping isis the the administrationadministration or or assumptionassumptionofof drugsdrugs or or biologicallybiologically and and

pharmacologicallypharmacologically activeactive substancessubstances and the and the useuse ofof medicalmedical actsacts withoutwithout anyany needneeduseuse ofof medicalmedical actsacts withoutwithout anyany needneed

justifiedjustified byby pathologicalpathological conditionsconditions and and ableabletoto modifymodify physicalphysical or or biologicalbiological conditionsconditions in in orderorder toto achieveachieve the best the best performancesperformances byby

the the athletesathletes””

Prof. Roberto Verna

The term The term dopingdoping comes from comes from ““doopdoop”,”, a mix a mix of of ergogenicergogenic substances that Dutch seamen substances that Dutch seamen used already four centuries ago before used already four centuries ago before

facing an ocean stormfacing an ocean stormProf. Roberto Verna

From From ““doopdoop””the term has the term has becomebecome“to dope”“to dope”and finallyand finally“doping”“doping”that meansthat meansthat meansthat meansa substance a substance able to modifyable to modifythe the performanceperformance

Prof. Roberto Verna

The The termterm dopingdoping comescomesalsoalso fromfrom ““oopoop””, a mix , a mix ofof opiumopium, , tobaccotobacco and and narcoticsnarcotics administeredadministeredtoto racehorsesracehorses in XIXth in XIXth centurycentury..centurycentury..

Prof. Roberto Verna

“Dope”“Dope” isis alsoalso anan ancientancient South South AfricanAfrican termtermindicatingindicating anan alcoholicalcoholic drink drink usedused toto

stimulatestimulate duringduring tribaltribal ceremonialceremonial dancesdances..Prof. Roberto Verna

Prof. Roberto Verna

•• In fact, doping substances In fact, doping substances are often drugs such as are often drugs such as Alcohol, Marijuana, Alcohol, Marijuana, Cocaine.Cocaine.

The The useuse ofof substancessubstances prohibitedprohibited forfordoping doping meansmeans beingbeing drugdrug--addictsaddicts

Cocaine.Cocaine.

•• These substances are These substances are always purchased and used always purchased and used secretly, secretly,

•• Because who uses doping Because who uses doping substances is aware of substances is aware of cheatingcheating

Prof. Roberto Verna

1. Before the match, during the training, totry to increase muscular mass andphysical strength or resistance

Types of doping related to the different moments of the agonistic

activity I

physical strength or resistance(steroids- EPO )

2. After the match, to recover strengthrapidly.

Prof. Roberto Verna

3.3. DuringDuring thethe match,match, toto::

•• DecreaseDecrease fatiguefatigue, ,

•• StimulateStimulate CNS, CNS,

TypesTypes of doping of doping relatedrelated to the to the differentdifferent momentsmoments of the of the agonisticagonistic

activityactivity IIII

•• StimulateStimulate CNS, CNS,

•• Reduce Reduce anxietyanxiety, in some , in some sportssports, ,

((cannabinoidscannabinoids, beta , beta blockersblockers, , etcetc))

•• TryTry toto increaseincrease oxygenoxygen transporttransport and and

reduce reduce fatiguefatigue ((hemotransfusionhemotransfusion))

Prof. Roberto Verna

History of History of DOPINGDOPING

Prof. Roberto Verna

Doping is an Doping is an ancient problemancient problem

Prof. Roberto Verna

From the Greeks…From the Greeks…Doping is not a recent Doping is not a recent discovery, but it was discovery, but it was already common among already common among antique antique GGreek wrestlers reek wrestlers (III century (III century b.Cb.C.) who .) who antique antique GGreek wrestlers reek wrestlers (III century (III century b.Cb.C.) who .) who used a mushroomused a mushroom--derived drug to enhance derived drug to enhance their aggressiveness.their aggressiveness.

Prof. Roberto Verna

Zeus sanctuary in Olympia

Prof. Roberto Verna

Callipateira of Rhodes

During their games, During their games, Roman athletes Roman athletes used different used different

…to the Romans…to the Romans

used different used different qualities of meat qualities of meat mixed with mixed with stimulating stimulating substancessubstances

Prof. Roberto Verna

Goat meat for the jumperGoat meat for the jumper

Antelope meat for the runnerAntelope meat for the runner

Bull meat for the wrestlerBull meat for the wrestler

…with…with breadbread and wineand wine

Milone di CrotoneMilone di CrotoneProf. Roberto Verna

The soldier of Marathon announces the victory, Jean-Pierre CORTOT, 1822-1834

Prof. Roberto Verna

The soldier of Marathon, Luc-Olivier Merson, 1869

Prof. Roberto Verna

Marathon in 1907

Prof. Roberto Verna

Leonida alle Termopili, Jacques-Louis David, 1814

Prof. Roberto Verna

Emperor Teodosio

and Holy Ambroseand Holy AmbroseAnton van Dick, 1620

Prof. Roberto Verna

An English bicycler,An English bicycler,

Arthur Linton, wins the Arthur Linton, wins the ParigiParigi--Bordeaux Bordeaux

in 1896 dying after the in 1896 dying after the race because of the use race because of the use

XIXXIXthth CenturyCentury

race because of the use race because of the use of exciting substances of exciting substances (ether(ether--cocaine)cocaine)

XXXXthth CenturyCentury

In 1904 Thomas In 1904 Thomas HicksHicks, , afterafter winningwinning the Olympic the Olympic marathonmarathonin in AthensAthens, , waswas seriouslyseriously takentaken illill byby the the useuse ofof stricnine stricnine

sulfatesulfate duringduring the racethe race

Again Again XXthXXth centurycentury

Dorando Dorando PetriPetri on on hishis marathonmarathon race race arrivalarrival, , (London 1908) (London 1908) wornworn--outout byby fatiguefatigue ‘cause ‘cause ofof the the

intakeintake ofof stricnine stricnine withwith cognaccognac

Prof. Roberto Verna

DOPING IN

SECRET SOCIETIES

Prof. Roberto Verna

Stimulating substances were

already used during WWII

Messerschmitt 109Messerschmitt 109

Messerschmitt 110Messerschmitt 110

to increase the reaction rate and decrease fear

LuftWaffeLuftWaffe fightersfighters flyingflying in British skiesin British skiesProf. Roberto Verna

BehindBehind the the strategicstrategic operationsoperations and the and the mostmost hazardoushazardousinterventionsinterventions the the useuse ofof stimulatingstimulating drugsdrugs waswas ableable toto

enhanceenhance everyevery decisiondecision and and actionaction thusthus makingmaking simplersimpler the the choicechoice toto diedie..

SoldiersSoldiers landedlanded fromfrom shipsships in in frontfront ofof NormandyNormandy shoresshorespushedpushed byby theirtheir heroismheroism, , butbut manymany withwith the the aidaid ofofchemicalschemicals usedused severalseveral timestimes byby various various armiesarmies..

Prof. Roberto Verna

DEXTROAMPHETAMINE DEXTROAMPHETAMINE isis a a drugdrug ableable toto spongespongeout out fatiguefatigue, , usefuluseful forforsoldierssoldiers in in missionmission

IRAQ IRAQ –– AFGHANISTANAFGHANISTANNew New frontiersfrontiers ofof MilitaryMilitary DopingDoping

ItsIts useuse hashas widelywidely spread non spread non onlyonly in in infantrymeninfantrymen butbut alsoalsoItsIts useuse hashas widelywidely spread non spread non onlyonly in in infantrymeninfantrymen butbut alsoalsoamongamong pilotspilots, , withwith enhancementenhancement ofof clearnessclearness and and quickerquicker

reflexesreflexes in the in the mostmost hazardoushazardous manoeuvresmanoeuvres..

Prof. Roberto Verna

In the post war In the post war periodperiod therethere waswas a a widespreadwidespread useuse ofofstimulatingstimulating drugsdrugs duringduring sport sport activityactivity. . HeavyHeavy upsetupset arosearoseforfor the the deathsdeaths ofof the the cyclistscyclists Alfredo Alfredo FalziniFalzini ((sympaminesympamineand and steanaminesteanamine) in ’49 at the end ) in ’49 at the end ofof the race the race MilanoMilano--RapalloRapallo, , KnudKnud JensenJensen ((amphetaminesamphetamines) ) OympicOympic gamesgames ’60, ’60, Tom SimpsonTom Simpson ((amphetaminesamphetamines) in ’67 Tour de France and ) in ’67 Tour de France and ofofthe the FrenchFrench soccer playersoccer player Luis QuadriLuis Quadri ((amphetaminesamphetamines) in ‘68) in ‘68

Simpson’s Simpson’s death ondeath on

Mont Mont VentouxVentoux

Prof. Roberto Verna

The The powerfulpowerful NationsNations

ForFor a long a long timetime the the powerfulpowerful NationsNations useduseddoping doping asas a State a State weaponweapontoto sorpasssorpass enemyenemycountriescountries::toto sorpasssorpass enemyenemycountriescountries::

DuringDuring the the SixtiesSixties and and the the SeventiesSeventies DDR, DDR, URSS, USA URSS, USA pushedpushed theirtheirathletesathletes toto winwin at at anyanycostcost

Prof. Roberto Verna

Former Former international international international international

efforts against efforts against dopingdoping

Prof. Roberto Verna

First cases of hematic doping

Ben Johnson lasts as Olympic champion for less than 24hs. He was suspended for the use of anabolyzing steroids

Following the dequalification, the Olympic gold has been attributed to Carl Lewis, example of honesty (15 years of career without doping).

Prof. Roberto Verna

Olympic Olympic GamesGames at Atlanta at Atlanta havehavebeenbeen namednamed “GH GAMES”“GH GAMES”

Prof. Roberto Verna

SheShe promisespromises toto

SYDNEY 2000SYDNEY 2000Cathy Freeman, Cathy Freeman, AustralianAustraliansprinter, sprinter, readsreads the the newnewOlympic Olympic oathoath::

SheShe promisespromises totoplay play withwith loyaltyloyaltywithoutwithout the the useuse ofofdoping doping toto improveimproveherher performance.performance.

Prof. Roberto Verna

RaducanRaducan, a , a RomanianRomanianathleteathlete awardedawarded withwiththe the goldgold medalmedal in in gymnasticsgymnastics isissuspendedsuspended forfor doping doping byby ephedryneephedryne, , usedusedbyby ephedryneephedryne, , usedusedtoto cure a cure a fluflu. . EphedryneEphedryne modifiesmodifiesthe the sensesense ofofequilibriumequilibrium and and isishazardoushazardous in in gymnasticgymnastic..

Prof. Roberto Verna

Three Three BulgarianBulgarianathletesathletes foundfoundpositive positive makemake allallthe the weightweight--liftersliftersteam team toto bebesuspendedsuspended..team team toto bebesuspendedsuspended..

The The RomaniansRomanians, in , in the the samesame conditioncondition, , paidpaid a fine and a fine and werewere ““forgivenforgiven””

Prof. Roberto Verna

WinterWinterOlympic Olympic gamesgames

•• First First appearanceappearance ofofNESP (NESP (DarbopoetineDarbopoetine), a ), a newnew moleculemolecule substitutingsubstitutingnewnew moleculemolecule substitutingsubstitutingEPOEPO

•• Salt Lake City Salt Lake City gamesgames: :

LazutinaLazutina, , DanilovaDanilova, , MuehleggMuehlegg ((darbopoetinedarbopoetine))

Lazutina Danilova

Prof. Roberto Verna

World World championshipchampionship ParisParis 2003 2003 –– casescases ofof doping doping byby ModafinilModafinil, a , a stimulatingstimulating moleculemolecule notnot includedincluded in in the the listlist ofof prohibitedprohibited substancessubstances; ; itit waswas includedincluded

sincesince AthensAthens 20042004

KelliKelli White White hadhad toto givegiveback 2 back 2 goldgold medalsmedals, 100 e , 100 e

200m200m

Calvin Harrison Calvin Harrison goldgold on on 4x400m4x400m

Prof. Roberto Verna

2003. New cases of positivity to Tetraidrogestrinone (THG)

Regina Regina JacobsJacobs1500m 1500m championchampion

KewinKewin TohtTohtshotshot putput

DwainDwain ChambersChambers100m 100m EuropeanEuropean

championchampion

The TGH was produced by BALCO laboratories headed

by nutritionist Victor Conte (KMA Club)Prof. Roberto Verna

ATHENS 2004ATHENS 2004Identified a significant number of doping cases that

have also led to the return of 7 illegally won medals

WilliamsRobert Fazekas

Irina Irina KorzhanenkoKorzhanenko ((StanozololoStanozololo)) goldgold medalmedalRobert Robert FazekasFazekas ((ControlControl adulterationadulteration)) goldgold medalmedalLuisa Calle WilliamsLuisa Calle Williams ((EptaminoloEptaminolo)) bronze bronze medalmedalOlenaOlena OlefirenkoOlefirenko ((EtamivanEtamivan)) bronze bronze medalmedal

Irina Korzhanenko

Prof. Roberto Verna

ATHENS 2004ATHENS 2004

Adrian Annus

Leonidas SabanisThe anti-doping controls will

have a retroactive effect and the

IOC reserves until 2012 to

withdraw the medals won in this

edition of the Games

Leonidas Sabanis ((Testosterone) bronze medalAdrian Annus (Refusal of the controls) gold medalFerenc Gyurkovics (Stanozolol) silver medal

Adrian Annus

Prof. Roberto Verna

Doping also affects the Paralympics

in Athens: two Azerbaijani

weightlifters were expelled from the

Games because positive to two

different substances. Sara Abbasov,

ATHENS 2004

Paralympics

different substances. Sara Abbasov,

28 y.o., and Gundula Ismaylov, 31

y.o. have fallen into the clutches of

the controls after a test conducted on

September 18th. The two tested

positive for nandrolone (the woman)

and stanozolol (the man).

Prof. Roberto Verna

OPERATION “QUADRIFOGLIO”

CARABINIERI FOR CARABINIERI FOR HEALTH (NAS)HEALTH (NAS)

Prof. Roberto Verna

-184 soldiers involved

-507 packs of prohibited medicines seized: (stimulants,

JUNE 6th 2001JUNE 6th 2001STARTING OF OPERATION QUADRIFOGLIO

PERQUISITIONS AT HOTELS IN SANREMO AND

NEIGHBOURING TOWNS

-507 packs of prohibited medicines seized: (stimulants,

anabolic steroids, steroids, diuretics, synthetic hemoglobin,

blood products)

Sequestration of large amounts of medical material

(syringes, needle-cannulas, etc.) and anonymous substances

for laboratory analysis

-105 people reported to the Judicial Authority

In January 2003 as part of the “Hercules” operation,

the Guardia di Finanza of Como

seized a huge load of human GH

from Lithuania intended for gyms

Imperia: thirty thousand

pills and eleven thousand vials

seized (anabolic drugs)

February 2004

Operation

"HERCULES"

Conducted by the NAS

Carabinieri in Ancona

Seizure of medicines of

anabolic action

Source:

- Italy

- Greece

- Tunisia

- Spain

- Romania

LIST OF THE DRUGS FOUND DURING “HERCULES” LIST OF THE DRUGS FOUND DURING “HERCULES” CONFISCATION OPERATIONCONFISCATION OPERATION

ALDACTONEALDACTONEANAPOLON TABLET ANAPOLON TABLET OKSIMETOLONOKSIMETOLONANDRIOLANDRIOLBENADONBENADONCLOMIPHENE CITRATECLOMIPHENE CITRATEDECADECA--DURABOLINDURABOLINDIANABOLDIANABOLDEPO MEDROLDEPO MEDROLEFEDRINA LEVELEFEDRINA LEVELEPARGRISEOVITEPARGRISEOVIT

LASIXLASIXHOMEOCUR TESTERSETHOMEOCUR TESTERSETHUMOLINHUMOLINJINTROPINJINTROPINKADIURKADIURKRIPTOCURKRIPTOCURISOPURAMINISOPURAMINLIPOSTABILLIPOSTABILMASTERONMASTERONMETADIENONMETADIENONMETANABOLMETANABOL

RESTANDOLRESTANDOLSAIZENSAIZENSCHERINGSCHERINGSYNFLEXSYNFLEXSOMATOSTATINASOMATOSTATINASPASMOBRONCALSPASMOBRONCALSPIROPENTSPIROPENTSUSTENONSUSTENONTAD 600TAD 600TIOSIDETIOSIDETITI--TRE LIOTIRONINATRE LIOTIRONINAEPARGRISEOVITEPARGRISEOVIT

ESICLENEESICLENEESTRUMATEESTRUMATEEUTIROXEUTIROXEXTRABOLINEEXTRABOLINEFELDENEFELDENEFINAJECTFINAJECTFINASTERIDEFINASTERIDEGANABOLGANABOLGENOTROPINGENOTROPINGH UMATROPEGH UMATROPEGLOBURENGLOBUREN

METANABOLMETANABOLMONORESMONORESNAPOPSINNAPOPSINNEOTONNEOTONNESPO 60NESPO 60NOVALDEXTAMOXIFENNOVALDEXTAMOXIFENPARABOLANPARABOLANPLACENTEXPLACENTEXPRIMOBOLANPRIMOBOLANPROFASI HPPROFASI HPPROCAR FINASTERIDEPROCAR FINASTERIDEPROVIRONPROVIRON

TITI--TRE LIOTIRONINATRE LIOTIRONINATESTEX ELMU TESTEX ELMU PROLONGATUMPROLONGATUMTESTOSTERONE CYPIONATETESTOSTERONE CYPIONATETESTOVIRONTESTOVIRONTESTOVISTESTOVISTRANSMETILTRANSMETILVENTIPULMIN CITRATEVENTIPULMIN CITRATEVIRORMONE TESTOSTERONE VIRORMONE TESTOSTERONE PROPINATEPROPINATEWINSTROLWINSTROL

APPROXIMATE AMOUNT APPROXIMATE AMOUNT : EURO 8.970.000,00: EURO 8.970.000,00Prof. Roberto Verna

JargonJargon wordswords usedused toto orderorder drugsdrugs, , recordedrecorded duringduring tappingtapping(COMANDO CARABINIERI PER LA SANITA' (COMANDO CARABINIERI PER LA SANITA' -- N.A.S.)N.A.S.)

EFEDRINAEFEDRINA MauMau--WangWangWINSTROLWINSTROL doubledouble U U -- dressesdresses -- STROMBASTROMBAGANABOLGANABOL ((forfor veterinaryveterinary useuse))DECADECA “the “the onesones withwith the yellow the yellow capcap" " --

masterizedmasterizedANDRIOLANDRIOL the motothe motoANDRIOLANDRIOL the motothe motoDECADURABOLINDECADURABOLIN the the carscarsNANDROLONE DECAONATONANDROLONE DECAONATO lat lat extensionextensionPROVIRONPROVIRON trouserstrousersOXANDROLONEOXANDROLONE lat lat machinemachineHASHISHHASHISH smokesmoke -- chocolatechocolateGHGH “the “the coldcold oneone" " –– the the iceice –– frozenfrozen proteinsproteins

–– chewingchewing gumsgumsPRIMOBOLANPRIMOBOLAN P P -- decaffeinateddecaffeinatedPROVIRONPROVIRON PROPROTESTOVISTESTOVIS ““thosethose withwith the the blueblue box”box”

Prof. Roberto Verna

Marion Jones

Every Sport Authority is bound to: Every Sport Authority is bound to:

•• Protect athletes’ healthProtect athletes’ health

•• Enforce medical and sports ethicsEnforce medical and sports ethics

•• Maintain the same opportunities for all the Maintain the same opportunities for all the athletes during a competitionathletes during a competition

Prof. Roberto Verna

WORLD ANTIDOPING ORGANISATION

WADA, Governments and Sport Organisations

World Antidoping Code

List of the Banned Drugs and Methods

Laboratory Accreditation

Random Controls

Intergovernative Institutions

Governments

Commission for the Vigilance of Doping

International federations

National Federations

National Antidoping

Laboratories

CIO Olympic Games

National Olympic

Committees

Commissions of the Sport Federations

Random Controls

The “medicalness” of the

athlete and of the sportsman

Prof. Roberto Verna

WHY DO ATHLETES AND SPORTSMEN USE WHY DO ATHLETES AND SPORTSMEN USE DRUGS?DRUGS?

•• ToTo improveimprove athleticathletic performanceperformance•• drugsdrugs prohibitedprohibited and and notnot forfor dopingdoping

•• creatinecreatine

•• linearlinear and and ramifiedramified aminoacidsaminoacids

••ForFor a a fasterfaster athleticathletic recoveryrecovery in case in case ofof strong strong athleticathletic involvementinvolvementathleticathletic involvementinvolvement

•• ErgogenicErgogenic AidsAids

•• ToTo recoverrecover losseslosses due due toto the intense the intense physicalphysical efforteffort•• VitaminsVitamins

•• MineralMineral SaltsSalts

•• ToTo protectprotect fromfrom oxydativeoxydative damagedamage•• VitaminsVitamins

•• AntioxydantsAntioxydantsProf. Roberto Verna

Drugs used by athletes and NOT

banned for doping

• Legal drugs

• Health products (supplements)

• Herbal products

• Homeopathic preparations

Prof. Roberto Verna

Athletes subject to doping controls

who reported taking medication

= 65= 65--70% (8000 70% (8000 athletesathletes))

Types of drugs reported

1,5%1,5%Herbals / homeopathic products

17%17%Vitamin supplements

20%20%Supplements (salt, amino acids, etc.).

35%35%Non-steroidal anti-inflammatory drugs

Prof. Roberto Verna

For a medication, adverse effects are allowed

only if the ratio risk / benefit of the treatment

is favourable.

A health benefit does NOT exist

in a subject who is not sickin a subject who is not sick

Unreasonable risk of ADR occurrence

Prof. Roberto Verna

What are the factors that

favour the spread of favour the spread of

doping?

Prof. Roberto Verna

The differences in performance

among athletes are minimal

• Fractions of seconds in speed trials

• Few seconds in endurance events

Consequence

Exasperated search of the smallest

improvement through the use of drugs

believed to be capable of increasing the

performance

Consequence

Prof. Roberto Verna

The obligation of results

Entire football teams are known taking energetic

substances to complete the season

Prof. Roberto Verna

The economic benefits and

reputation

Kournikova

The sponsors pay sports champions very

well, but only as long as the champions win

Prof. Roberto Verna

The increase in training

In some sports the

workload to stay at

the top can be

Comaneci

the top can be

sustained only by

resorting to drug aid

Prof. Roberto Verna

The effect of

stress and lack of

psychological

preparation for

Michael Johnson

preparation for

Prof. Roberto Verna

The pressure of parents...

Often parents demand from

children a sporting career

as champions, even

accepting the use of doping accepting the use of doping

to achieve their dreams

Prof. Roberto Verna

...Or their lack of interest

• OTHER TIMES THE

YOUNG RESORT TO

DOPING WITHOUT DOPING WITHOUT

ANYONE AROUND

HIM KNOWS IT

Prof. Roberto Verna

The The useuse ofof prohibitedprohibitedsubstancessubstances isis anan admissionadmission

ofof fearfearJenny Gale

Prof. Roberto Verna

NotNot toto acceptaccept the the duelduel, the , the defeatdefeat, the , the

victoryvictoryProf. Roberto Verna

Cases Cases ofof positivitypositivity toto some “social” some “social” drugsdrugs, , suchsuch asascannabis and cannabis and cocainecocaine in the English Premier Leaguein the English Premier League

FormerFormer Chelsea Chelsea GoalkeeperGoalkeeper Mark Mark BosnichBosnich

positive positive toto cocainecocaine

Lee Lee BowyerBowyer todaytoday at at Newcastle Newcastle UnitedUnited positive positive

toto MarijuhanaMarijuhanaProf. Roberto Verna

The “medicalization” of sports

facilities

• Some gyms are a mix

between spatial structures

and back-room

pharmacies.

You can find anything

and almost nothing is safe

Prof. Roberto Verna

To combat doping it is

necessary to know

the effects and the effects and

damage of banned

substances

Prof. Roberto Verna

Classes of substances

prohibited in-competition only

•• STIMULANTS

• NARCOTICS• NARCOTICS

• CANNABINOIDS

• GLUCOCORTICOSTEROIDS

Prof. Roberto Verna

Classes of substances prohibited in

and out of competition

� ANABOLIC AGENTS

� DIURETICS AND MASKING AGENTS

� PEPTIDE HORMONES� PEPTIDE HORMONES

� BETA-2 AGONISTS

� ANTIESTROGENIC AGENTS

Prof. Roberto Verna

Classes of substances

prohibited only in certain

sportsALCOHOLALCOHOLAeronautics

Archery

Motoring

Billiards

BETABLOCKERSBETABLOCKERS

Football

Gymnastics

Modern Pentathlon

Motorcycling

Aeronautics

Archery

Motoring

BilliardsBilliards

Football

Gymnastics

Karate

Modern Pentathlon

Motorcycling

Skating

Triathlon

Wrestling

Motorcycling

Bowling 9 Pins

Sailing

Shooting

Swimming

Wrestling

Billiards

Bobsleigh

Bridge

Curling

Prof. Roberto Verna

Methods prohibited in and out competition

ENHANCEMENT OF OXYGEN TRANSFER

Blood doping: use of autologous, homologous or heterologous red blood cell

products of any origin, outside of legitimate medical treatment

Use of products that enhance the uptake, transport or delivery of oxygen (eg

erythropoietin), hemoglobin products, including but not limited to

hemoglobin-based blood substitutes, microencapsulated hemoglobin

products, perfluorochemicals, and efaproxiral (RSR13)

DRUG, CHEMICAL AND PHYSICAL HANDLING

Is the use of substances and methods that can alter the integrity

and validity of specimens collected in doping controls (intravenous

infusion, catheter and replacement of urine)

GENE DOPING

And the non-therapeutic use of genes, genetic elements and / or cells

that have the capacity to enhance athletic performance

Prof. Roberto Verna

It has recently been applied a mark on the packaging of pharmaceutical

products that contain substances prohibited for DOPING:

The mark is accompanied by the following warning:

“For those who play sports:

the use of the drug without therapeutic need

may result in positive test”

BE FAIR AND TAKE CARE OF YOUR

HEALTH!

Prof. Roberto Verna

HEMATOCHEMICAL MARKERS OF THE

PHYSICAL CONDITION OF THE ATHLETE

• Testosterone

• Dihydrotestosterone

• ACTH

• Cortisol

• Evaluation of the

agonistic stress and

involvement

• Cortisol

• DHEAs

• delta-4-

androstenedione

• GH

Prof. Roberto Verna

HEMATOCHEMICAL MARKERS OF THE

PHYSICAL CONDITION OF THE ATHLETE

• LDH

• CPK

• Study of the

muscular

characteristics of an

athleteathlete

Prof. Roberto Verna

MOUNTAIN SPORTS

• Complete Blood Count

• Iron

• Transferrin• Transferrin

• Ferritin

• Hb dissociation curve

• Diphosphoglycerate

Prof. Roberto Verna

Prohibited substances

• Stimulants

• Narcotics

• Anabolizing Agents

• Diuretics

• Peptide Hormones,

mimicking substances

Prohibited methods

• Administration of blood,

RBCs and/or similar

products)

• Administration of

INDICATORS OF THE USE OF PROHIBITED SUBSTANCES AND METHODS

mimicking substances

• Local Anestetics

• Alcohol

• Cannabis sativa and

indica

• Glucocorticosteroids

• Beta-blockers

artificial oxygen

transporters or plasma

substitutes

Reduced fatigue, euphoria

Increased

heart rate

Heatstroke

Excitement,

restlessness,

insomnia,

EFFECTS ADVERSE EFFECTS

Marked effect on

stimulating the central

nervous system

(increases the

competitiveness of

Central Nervous System

Tremors, Agitation,

Aggressiveness

Loss of Critical Sense

Headache

Insomnia

STIMULATING AGENTS

Amphetamine, Ephedrine, Cocaine …

insomnia,

aggressiveness

Dependence

Addiction

Dispnea

competitiveness of

attention, sense of well

being, euphoria)

Decreased fatigue

Increased heart rate

Increased blood glucose

and free fatty acids

Reduced sense of hunger

(anorectic effect)

Vomiting, Anorexia

Hyperthermia (Heat Stroke)

Seizures

Deep depression, Psychosis

Cardiovascular System

Vasoconstriction

Hypertension

Tachycardia

Rhythm Disturbances

Myocardial Infarction

Stimulation

of energetic

metabolism

Vomiting

Prof. Roberto Verna

STIMULANTS

• Amphetamines are a class

of stimulants used in many

sports for their ability to

increase alertness,

Prohibited only in competition

increase alertness,

competitiveness, reduce

fatigue, give a sense of

euphoria by stimulating the

energy metabolism

Prof. Roberto Verna

Amphetamines damage:

Excitement

Restlessness

Insomnia

Aggressiveness

dental injury by ecstasy

Addiction

Psychosis

Convulsions

Depression

Anorexia

Prof. Roberto Verna

Effect of ecstasy on the spider’s ability to

weave the cloth

after ecstasybaseline

Prof. Roberto Verna

Side Effects

BRAIN HEMORRHAGE FROM COCAINE

Prof. Roberto Verna

� 5-HIAA 5-hydroxyindoleacetic acid - a breakdown product of

serotonin.

�� 5-HT

(levels lower in CSF during the intervals between administration)

Stimulants – blood parametersECSTASY - MDMA – Methilenedioxymethamphetamine

studies in rats

(levels lower in CSF during the intervals between administration)

�� Norepinephrine

� Epinephrine

� Dopamine

Suppression of IFN gamma and IL-10 production in coltures

Neuronal toxicity of the molecule induces serotonin depletion

� Nausea, Vomiting

Stimulants - Ephedrine

Short-term adverse effects

� Nausea, Vomiting

� Increased sweating

� Thirst

� Restlessness, Insomnia

� Tachicardy, Hypertension, Arrhythmias.

Prof. Roberto Verna

Increased

tolerance to

Mood disorders

Depression of

respiratory function

Interference in the

central nervous system

with increased

tolerance of pain

Bronchospasm

Depression of

respiratory function

Nausea, vomiting

NARCOTICS

Heroin, Methadone and Morphine…

Constipation

tolerance of pain Nausea, vomiting

Constipation

Decreased urine flow

Increased sweating

Drooling

Changing mood

Addiction

Nausea

Vomiting

Bronchospasm

Prof. Roberto Verna

Its removal may lead the athlete to "overdo"

Pain is a warning sign

NARCOTICS

Are taken to reduce pain perception

Prohibited only in competitionProhibited only in competition

The risks are:

worsening of existing injuries

causing permanent damage.

Prof. Roberto Verna

• Constipation;

• Nausea and vomiting;

• Insomnia and depression;

NARCOTICSADVERSE EFFECTS

• Decreased ability to concentrate;

• Loss of balance and coordination;

• Addiction;

• Reduced heart rate;

• Bradypnea

Increased sense

of wellbeing

Euphoria

Anxiety

Euphoria

Drowsiness

Apathy

CANNABINOIDS

Hashish, Marijuhana …

Reduced ability

to coordinate

Altered

perception

Euphoria and

wellbeing

It is hypothesized

a decrease in emotional

tension before the race

Apathy

Tachycardia

Orthostatic Hypotension

Dependence

Memory deficits

Psychosis

Schizophrenia

Teratogenic to the foetus

Carcinogen (because it is

smoked)

perception

of time

Personality

changes

Balance

disorders

Prof. Roberto Verna

CANNABINOIDSCANNABINOIDS

Marijuana and hashish

distort perceptions and do

not allow proper risk

assessment.

The athlete perform actions

(stunts) that would not do

under normal conditions.

Prof. Roberto Verna

A decrease of emotional tension before a race is postulated.

� Increased heart rate, blood pressure;

� Balance and coordination disorders;

CANNABINOIDS

SPECIFIC ADVERSE EFFECTS

� Short-term memory loss;

� Loss of concentration, hallucinations, psychosis;

� Subnormal body temperature;

�Abnormal spermatogenesis and ovulation.

Prof. Roberto Verna

Euphoria

Powerful anti-

inflammatory action

Euphoria

Increased ability to

Alteration of

Electrolyte Balance

Hypertension

Hyperglycemia

GLUCOCORTICOSTEROIDSprohibited per oral, rectal, im. or iv. assumption

medical certification is required for other administration

Osteoporosis

Alteration of

the electrolyte

balance

HypertensionIncreased

ability to resist

to noxious Increased ability to

resist to noxious

stimuli

Hyperglycemia

Hyperlipidemia

Hyperuricemia

Increased Susceptibility

to Infections

Peptic Ulcer

Osteoporosis

Insomnia

Cataract

Peptic

Osteoporosis

Increased

Susceptibility

to Infections

Hyperglycemia

Anti-inflammatory action

to noxious

stimuli

Prof. Roberto Verna

GLUCOCORTICOSTEROIDSGLUCOCORTICOSTEROIDS

• Treatment of acute

• Anti-inflammatory

• Euphorizing effect

• Reducing the

perception of fatigue

Prof. Roberto Verna

• Electrolyte Disorders

• Heart Failure

• Osteoporosis

GLUCOCORTICOSTEROIDSGLUCOCORTICOSTEROIDSadverse effects

• Osteoporosis

• Immunosuppression

• Renal Failure

• Amenorrhea

Prof. Roberto Verna

Insomnia;

Hypertension;

GLUCOCORTICOIDS

ADVERSE EFFECTS

Hypertension;

Cataracts;

Diabetes Mellitus;

Osteoporosis;

Immunosuppression

Prof. Roberto Verna

Tests to reveal the use

of Corticosteroids

• Blood Glucose (I)

• Blood Potassium (L)

Tests to reveal the use

of Narcotics and

Analgesics

• LH

• ADH

• GH

• Prolactin • Blood Potassium (L)

• Blood pH (I)

• Prolactin

• Testosterone

Prof. Roberto Verna

ANABOLIC DRUGS

Mr. OlympiaMr. OlympiaMs. OlympiaMs. OlympiaLenda MurrayLenda Murray

Ronald ColemanRonald Coleman

Prohibited “Prohibited “inin--out”out” competioncompetion

Are steroid hormones (testosterone, nandrolone and so on) that strengthen the

muscles and reduce fat.Prof. Roberto Verna

On the other hand,

they are carcinogenic

to the liver, addictive,

cause changes in sexual

characteristics

ANABOLIC DRUGSProhibited “in-out” competion

characteristics

producing feminization

in boys and vice versa.

Prof. Roberto Verna

Disciplines more exposed to their use:

Weightlifting

Shot put

Discus Throw

Bodybuilding

Football

Wrestling

Prof. Roberto Verna

•• Human chorionic gonadotropin (HCG):

•�� the synthesis of testosterone

contrast to the testicular atrophy

Drugs often used in combination

contrast to the testicular atrophy

•• Diuretics:

•�� water retention

dilute the urine for drug tests

Prof. Roberto Verna

•• AntiestrogensAntiestrogens: :

• prevent gynecomastia in males

Drugs often used in combination

•• ACTH:ACTH:

• �� endogenous steroids production

can provoke a feeling of euphoria

Prof. Roberto Verna

Long bone growth block

EFFECTS Adverse effects

Increased muscle mass

Decreased fat mass

Increased fatigue

Decreased catabolic

In males (pre-puberal)

Early epiphyseal cartilage

welding (block long bone

growth)

Inhibition of spermatogenesis

In males (adults)

Oligospermia / azoospermia

ANABOLIC AGENTS

Testosterone, Nandrolone, Stanzolol…

Increased

synthesis of

red blood cells

Increased

bone density

Impaired reproductive

function

Decreased catabolic

action of

glucocorticoids

Increased synthesis of

red blood cells

Increased bone

density

testicular atrophy

Prostatic hypertrophy

Abnormal liver function with

the possibility of tumors

Increased plasma lipid

In women

Suppression of ovarian function

Atrophy of the mammary gland

Virilization

Abnormal liver function with

the possibility of tumors

Liver damage

Increase of TG and Chol

Muscle mass

Fat mass

Tendon injury

Prof. Roberto Verna

Testosterone increases

muscle mass and

changes the behavior

with manifestations of

Ben Johnson

ANABOLIC DRUGSProhibited “Prohibited “inin--out”out” competioncompetion

with manifestations of

irritability,

aggressiveness and

violence.

Prof. Roberto Verna

Precursors of

nandrolone

The story of the players

Guardiola, Stam, de Boer,

Monaco, Couto, Davids, Monaco, Couto, Davids,

Bucchi, (tested positive for

nandrolone for taking

supplements made in the

USA polluted with

precursors of nandrolone) is

well known.

Prof. Roberto Verna

Other and more recent cases of

nandrolone in soccer

Emanuele BlasiEmanuele BlasiMohamed KallonMohamed Kallon Saadi GheddafiSaadi Gheddafi

Prof. Roberto Verna

Bohdan UlirachBohdan Ulirach

20032003

NANDROLONE LANDS IN TENNIS

20042004

McEnroe admits that he Bohdan UlirachBohdan Ulirach McEnroe admits that he

discovered he had taken

substances used in horse

racing

Greg Rusedski in 2004, one of the 47

positive players among the top 120 of

the ATP ranking

Prof. Roberto Verna

ANABOLIC STEROIDS

Jennifer

Capriati

Can transform an athlete

in less than two years

Prof. Roberto Verna

The use of steroid hormones is so effective...

...that they can transform a woman

Heidi Krieger

transform a woman directly into a man, as Heidi Krieger.

Prof. Roberto Verna

Andreas Krieger (39) today with his wife Ute

Winter

Heidi Krieger goldmedal in putting theshot at Europeangames in 1986 whenshe was 21

Corriere della sera 4 maggio 2003

Prof. Roberto Verna

�� muscle mass

� body fat

� stamina

Anabolic Agents(testosterone, nandrolone, stanzolol…)

� stamina

� aggressiveness

� catabolic action of glucocorticoids

� synthesis of red blood cells

� bone density

Long lasting use

Mental Damage:

Dysphoria

Psychosis

Dependence

Severe Depression

ANABOLIC AGENTSProhibited “in-out” competition

Liver Damage:

Cholestasis

Hepatitis

Benign and Malignant Tumors

Cardiovascular Damage:

Cardiomyopathy

Acute Myocardial Infarction

Cerebrovascular Accident

Pulmonary Embolism

Prof. Roberto Verna

Adverse effects of using anabolic agents depend on

the age and sex of the subject, the duration of

treatment, the dose and type of steroid used

Anabolic Agents

Adverse effects can be divided into

• generic

• specific to men

• specific to women

General adverse effects

�Acne;�Damage to the Reproductive System and Sterility;�Hypertension;

Anabolic Agents

�Hypertension;�Increased Risk of Cardiovascular Disease;�Abnormalities and Renal and Liver Dysfunction;�Aggressive and Violent Behaviour;�Tendon Injury and/or Bone Microfractures

Adverse effects specific to men

Gynecomasty;

Reduced Production of Male Hormones;

Anabolic Agents

Reduced Production of Male Hormones;

Testicular Atrophy and Oligo/azoospermia;

Infertility, Impotence;

Alopecia;

Increased Risk of Prostate Cancer.

Adverse effects specific to women

� Hirsutism and Hair Loss;� Menstrual Irregularities and Amenorrhea;

Anabolic Agents

� Menstrual Irregularities and Amenorrhea;� Atrophy of the Mammary Glands;� Voice Change;� Clitoris-megalia

�� Haematocrit�� Platelets

�� Levels of FSH and LH

Anabolic Agents

General Haematochemical Alterations

�� Levels of FSH and LH

�� Testosterone levels

�� HDL-cholesterol and total cholesterol

�� Glycemia, Insulinemia

�� Liver enzymes and indices of cholestasis

Analytes specific for anabolyzing substances

• FSH ↓

• LH ↓

• PT ↓

• PTT ↓

• Tot. Chol. ↓

• Testosteron ↓

• Estradiol ↓

• Estrone ↓

• LDL Chol ↑

• C- Prot

Prof. Roberto Verna

• Tot. Chol. ↓

• HDL Chol ↓

• GH

• CPK ↑

• AST - ALT ↑

• LDH ↑

• Total Proteins

• C- Prot

• S-Prot

• D-Dimer

• PAI-1

• ATIII

• APO A ↓

Alterated

hydro-saline

balance

Dehydration

Collapse

EFFECTSADVERSE EFFECTS

Decreased excretion of

other prohibited

substances in the urine,

masking the presence

Alteration of the hydro-

saline equilibrium

Dehydration, collapse

muscle cramps

Fatigue

Alteration of the

MASKING AGENTS

Diuretics, Epitestosterone, Probenecid,

Plasma expanders (dextran, hydroxyethyl-starch)

Alterated

hormonal

haematological

parameters

Increased

excretion

Collapsemasking the presence

Alteration of the

hormonal and

hematological

parameters

Removal of fluid

resulting in loss of body

weight (sport weight

category)

Alteration of the

metabolism of sugars

and fats

Increased uric acid

Formation of kidney

stones, Kidney damage

Hypersensitivity reactions

lesions

Muscle cramps and

fatigue

Prof. Roberto Verna

They have the ability to

• alter the excretion of

prohibited substances,

mask their presence in urine

Zhang Yi

MASKING AGENTS

Prohibited “in-out” competition

• mask their presence in urine

or other samples used in

doping control,

• or modify the hematological

parameters

Prof. Roberto Verna

Useful to decrease weight in the orders divided by classes

• Dehydration

• Amenorrea

Ivan Ivanov

MASKING AGENTSProhibited “in-out” competition

• Amenorrea

• Anemia

• Electrolyte Dysequilibrium

• Osteoporosis

• Hypotension

Prof. Roberto Verna

Tests able to detect the use of diuretics

• Na

• Cholesterol

• Ht

• Uric acid

• Glucose

• Urinary aldosterone

• Na, K Pump

• Na, K Cotransport• Plasma and

Urine electrolytes

• 17-OH corticosteroids

• Urine pH (or blood)

• Na, K Cotransport

Prof. Roberto Verna

• Small protein molecules made by biotechnology:

• GH

• GONADOTROPINS

PEPTIDE HORMONESProhibited “in-out” competition

• GONADOTROPINS

• ERYTHROPOIETIN

• INSULIN

THE DARKER SAMPLE CONTAINS BLOOD SO DENSE THAT IT DOES NOT COME DOWN ON TURNING THE TUBE UPSIDE DOWN

Prof. Roberto Verna

GH and gonadotropins have the same effects as testosterone: they are anabolizing agents but

PEPTIDE HORMONESProhibited “Prohibited “inin--out”out” competitioncompetition

anabolizing agents but block growth of long bones, generate gynecomasty, depression, testicular atrophy and hepatic tumors.

Prof. Roberto Verna

Long bone

growth block

Euphoria

Depression

•In males promote the

production of

testosterone by the

In pre-puberal

Early epiphyseal cartilage

welding (block long bone growth)

Inhibition of spermatogenesis

in adulthood

Testicular atrophy

PEPTIDE HORMONES

Chorionic gonadotropin (HCG) and synthetic pituitary hormone (LH)

Stimulation of

testosterone production

Damage

to reproductive

function

testosterone by the

testisTesticular atrophy

Prostatic hypertrophy

Abnormal liver function with the

possibility of tumors

Increased plasma lipid

States of euphoria and depression

Gynecomastia

Precocious puberty in adolescents

Liver damage

Increased

triglyceride

and cholesterol

Prof. Roberto Verna

Dizziness

Euphoria

Headache

Insomnia

Increases the ability to

withstand stress

Anti-inflammatory

action

Hypertrophy of the adrenal

cortex

Osteoporosis

Myopathies

Damage to the gastro-

intestinal Peptic ulcer

PEPTIDE HORMONES

Corticotropin (ACTH)

Gastritis

Tendency

to diabetes

action intestinal Peptic ulcer

Shiny skin

Headache

Reduced tolerance to

carbohydrates

Dizziness

Euphoria, insomnia

Obesity

Gastritis

Muscular and bone fragility

Hypertrophy

of the

adrenal cortex

Increased

stress tolerance

Anti-inflammatory

action

Prof. Roberto Verna

CardiopathyHypertension

Increased protein

synthesis

Increased muscle

tissue growth

Acromegaly in adults

Fluid retention and edema

(generalized and

peripheral)

Arthritis, carpal tunnel

PEPTIDE HORMONES

Growth hormone (GH) growth factor (IGF-1)

Increased protein synthesis

Diabetes

Muscular and joint damage

tissue growth

Increased height

growth in the young

(gigantism)

Increased lipolysis

Increased blood

glucose

Arthritis, carpal tunnel

syndrome

Cardiomyopathy

Hypertension

Hyperglycemia Diabetes

Increased hands and feet size

Increased volume oforgans

Stimolated bone growth

Increased release

of circulating

energy intake

Diabetes

Prof. Roberto Verna

Tests able to detect the use of GH

• GH

• LH

• FSH

• Cholesterol

• IGF-1

• IGF- BP2

• IGF – BP3

• NEFA • Cholesterol

• TG

• Creatinine Clearance

• BUN

• Glucose

• Insulin

Prof. Roberto Verna

Death for doping“Flo Jo” Griffith (1959-1998) caught an infectious disease because of the abuse of growth hormone extracted from corpses.

She said:“when you always get second, you can accept it or try to become the number one”.

Prof. Roberto Verna

•Enhances glucose

uptake by the tissues

(mainly muscle,

adipocytes and liver)

•Hypoglycemic crisis (Arrhythmias, Cardiomiopathy, Coma, Death)

PEPTIDE HORMONES

Insulin

Stimulates protein synthesis

Hypoglycemia

adipocytes and liver)

•Stimulates protein

synthesis

•Hypoglycemia

induces GH release

Coma, Death)

• Inhibition of endogenous production

•Hepatic damage

Endogenous synthesis inhibition

Increases tissue uptake of glucose

Prof. Roberto Verna

•Stimulus to

erythropoiesis

•Increases oxygen

•Polyglobulia

• Increase of blood viscosity

•Myocardial Infarction

PEPTIDE HORMONES

Erythropoietin (EPO)

PoliglobuliaThrombosis

•Increases oxygen

transport capacity •Thrombosis

• Ictus

•Pulmonary embolism

•Seizures

ThrombosisCardiac failure

Stimulates erythropoiesis

Prof. Roberto Verna

EPO increases erythrocyte

production thus oxygen

transport.

On the other hand, EPO makes

PEPTIDE HORMONESProhibited “in-out” competition

blood dense like marmalade:

the risk of death by thrombosis

increases by 400%

Prof. Roberto Verna

Tests revealing the use of EPO and analogues

• Peripheral blood examination

including RBC indices

• Reticulocytes ↑

• Transferrin

• Ferritin

• Folic Acid• Folic Acid

• Vitamin B12

• Iron

• CD 71

• Glycophorin A

• Bilirubin

• CFU-E

• BFU-EProf. Roberto Verna

Broncodilation

Cardiostimulatingaction

Agitation

Irritability

Insomnia

Heart rhythm

disorders

Bronchodilation

Increasing the efficiency

of Myocardial Contractility

Lipolytic Action

(Increase of Free Fatty

Tremors, Agitation,

Irritability and Insomnia

Hyperhidrosis

Drooling

Urinary Retention

Beta 2 agonists

Stimulating and Anabolic Action

disorders

Urinary retention

(Increase of Free Fatty

Acids)

Hypertrophy

of Type II Muscle Fibers

Urinary Retention

Anorexia

Hypokalemia

Alterations in Blood Pressure

Tachycardia and

Rhythm Disturbances

Dyspnea

hidrosis

Type II muscle

fiber hypertrophy

Lipolytic action

Prof. Roberto Verna

BETABETA--2 AGONISTS2 AGONISTS

THESE DRUGS HAVE AN EFFECTIVE

ACTION ON THE MUSCLE MASS WITHOUT

DETERMINING THE MANY SIDE EFFECTS

RELATED TO THE USE OF STEROIDS.

They are also used to prevent asthma triggered by

exercise

Prohibited “Prohibited “inin--out”out” competioncompetion

Growth in mass and

increased muscle strength

exercise

Clenbuterol produces a specific

protein anabolism in both normal

muscle and in the catabolic phase

through the activation of beta-2

adrenergic receptors present in

skeletal muscles themselves

Prof. Roberto Verna

Therapeutic dose range:

20-80 micrograms per day

Doses in doping:

100-140 micrograms per day

BETABETA--2 AGONISTS2 AGONISTSProhibited “Prohibited “inin--out”out” competioncompetion

SIDE EFFECTS: Tremor (very marked), and

cardiovascular effects such as tachycardia, palpitations,

arrhythmias, hypertension. Anxiety, dizziness, headache,

insomnia and muscle spasms were also observed.

Prof. Roberto Verna

Alopecia

Liver anomalies

Indirect

anabolyzing

capacity

Nausea and vomiting

Headache and dizziness

Leukopenia

Thrombocytopenia

AGENTS WITH ANTIESTROGEN ACTIVITY

Aromatase inhibitors, clomiphene, cyclophenil

Nausea andVomiting

capacityThrombocytopenia

Severe skin reactions

Alopecia

Liver impairment

LeucopeniaThrombocytopenia

Indirect anabolyzing capacity

Prof. Roberto Verna

ANTIESTROGEN AGENTSANTIESTROGEN AGENTS

Prohibited in and out competition,

exclusively for men

Clomiphen

Prohibited in and out competition

Cyclophenil

Raloxifen

Tamoxifen

Toremifen

Aromatase inhibitors (Aminoglutethimide, Anastrozole, Exemestane,

Letrozole, Fludrocortisone and Desossicortone)

Prof. Roberto Verna

Taken in small doses

it reduces anxiety and

nervous tension Depression of the

ALCOHOL

Depression of reflex activities

Reduced

anxiety and

nervous

tension

nervous tension

Increased self

confidence

Depression of the

nervous system

Impaired coordination

Liver damage

Altered coordination

Prof. Roberto Verna

ALCOHOLALCOHOL

Alcohol activates the

ventral area of the

brain and releases

Prohibited in particular sportsProhibited in particular sports

brain and releases

dopamine by

changing all the

positive feelings

Prof. Roberto Verna

Damage from alcohol

include severe liver

disease and risk for

infants of drinker

ALCOHOLALCOHOLProhibited in particular sportsProhibited in particular sports

infants of drinker

mothers: the foetal

alcohol syndrome

Prof. Roberto Verna

Anxiety decrease

Reduction in blood

pressure

Decreased heart rate

Reduced contractility of

Negative effect on

aerobic performance

Increased perceived

exertion

BETABLOCKERS

Lightheadedness

Increased fatigue

Reduced contractility of

the heart

Reduction of oxygen

consumption

Reduction of tremor

Reducing anxiety

exertion

Bronchospasm in

patients with asthma

Bradycardia

Hypotension

Insomnia

Impotence

Possibility of

cardiac arrest

of bronchospasm

and hypoglycemia

Reduced cardiovascular activity

Reduced

aerobic

performance

Prof. Roberto Verna

BETABLOCKERSBETABLOCKERS

Beta-blockers reduce tremor with great

effectiveness, and are used in shooting

competitions

Prohibited in particular sportsProhibited in particular sports

Prof. Roberto Verna

• On the other hand, beta

blockers may cause heart

failure, bronchospasm

and even death.

BETABLOCKERSBETABLOCKERSProhibited in particular sportsProhibited in particular sports

and even death.

• Depression,

hallucinations, seizures

and alopecia are also

reportedProf. Roberto Verna

Tests to detect the use of beta-blockers

• TSH

• fT3

• fT4

• HDL-Chol

• TG

• Insulin

• Renin

• Emogas analysis

Prof. Roberto Verna

• TG

• NEFA

• Glucose

SPORTS YES, DOPING NO

DOPING IN SPORT IS A CRIME

AND MAY SERIOUSLY HARM

YOUR HEALTH

Prof. Roberto Verna

Genetic DopingGenetic Doping

chromosomes

genome

genes contain

instructions for

protein productionDNA

proteins

The proteins act alone or

in many cellular

functions in order to

explain complex

Prof. Roberto Verna

Genetical manipulation.Genetical manipulation.Which should the limit be?Which should the limit be?

Prof. Roberto Verna

• Based on the manipulation of genes.

• Using the results obtained in gene

therapy.

Genetic DopingGenetic Doping

therapy.

• Is it a future threat for athletes?

Prof. Roberto Verna

Gene TherapyGene Therapy• Artificial insertion of genes into the body of the patient.

Purpose:

• Kill or weaken cancer cells.• Kill or weaken cancer cells.

• Making the body able to reproduce on its own substances now available only on administration.

• Replace defective genes with healthy copies.Problems: lack of control on the expression of artificial gene.

Prof. Roberto Verna

The structure of a Gene

DNADNA

Control regioncoding region

RNARNA

ProteinProtein

Prof. Roberto Verna

How is an artificial gene

introduced ?

1. Direct injection of DNA into muscle structures

2. By inserting genetically modified cells2. By inserting genetically modified cells

3. Introduction of the gene in the organism using a virus

as a vector

Prof. Roberto Verna

Direct injection of DNA into a

muscle

Prof. Roberto Verna

muscle

Prof. Roberto Verna

Quadriceps mouse Quadriceps mouse muscle after a single muscle after a single

muscle

Danko et al. Human Molecular Genetics (1997) 6:1435-1443

muscle after a single muscle after a single injection of a plasmid injection of a plasmid containing a gene, containing a gene,

evidenced by the blue evidenced by the blue color (color (lacZlacZ))

Prof. Roberto Verna

Inserting genetically modified

Prof. Roberto Verna

Using a virus as a vector

Prof. Roberto Verna

Using a virus as a vector

Prof. Roberto Verna

The prospect of gene

doping

• An alternative to the administration of drugs

that the body can produce itself

• Changing the natural regulation of genes

• Enhancement of proteins in the body

Prof. Roberto Verna

Examples of the potential of

gene doping

• Increase in hematocrit by EPO

• Increased muscle strength by IGF-1

• Increased muscle mass by the removal of • Increased muscle mass by the removal of

myostatin

• Increased blood flow through VEGF

Prof. Roberto Verna

Gene therapy using EPO

Monkeys

EMATOCRITO

Zhou et al. Gene Therapy (1998) 5:665-670

Monkeys

inoculated with a

virus carrying the

gene for EPOEMATOCRITO

WEEKS AFTER INOCULATION

Prof. Roberto Verna

Mice inoculated with a

virus carrying the gene

for IGF-I

Gene therapy using IGF-I

Barton-Davis et al. Proc.Natl.Acad.Sci. (1998) 95:15603-15607

Prof. Roberto Verna

Removing the gene that controls the

growth of muscle mass (myostatin)

Foreleg of a Foreleg of a Foreleg of a

normal mouse

Lee et al. Curr. Opin. Gen. Dev. (1999) 9:604-607

Foreleg of a

mouse lacking

the myostatin

Prof. Roberto Verna

VEGF gene therapy on

humans

Blood vessels of a patient

Baumgartner et al. Circulation (1998) 97:1114-1123

AfterAfter

Blood vessels of a patient

who received the

inoculation of a virus

carrying the gene for

BeforeBefore

Prof. Roberto Verna

Can we discover

genetic doping?• The protein produced is equal to the endogenous

protein

• The artificial DNA is present only locally after an

injection with pure DNA or genetically modified

cellscells

• You should know the sequence of artificial DNA

to be able to detect it

Prof. Roberto Verna

POSSIBLE COUNTERMEASURES

• Making the gene doping illicit

• Establish close contacts with companies that

produce gene therapies

• Developing DNA tests that can detect artificial

genes used in gene therapygenes used in gene therapy

• Developing indirect methods to detect gene doping,

if possible

Prof. Roberto Verna

WHEN?WHEN?• Gene doping is already present and it

constitutes a serious risk to the athlete

• It will be easier when gene therapy

becomes a standard procedure

(in 10-20 years)

Prof. Roberto Verna

THANK YOU FOR YOUR

ATTENTIONATTENTION

THE PROBLEM OF FOOD

SUPPLEMENTS

The world of sport, professional or not, looks for a

"magic" and harmless ingredient that can improve

physical performance and increase the level of

competitiveness

Companies promote the spread of specialized

products designed specifically for sports

These substances are not always safe

Prof. Roberto Verna

Recently, the European Directive on food supplements

(46/2002/EC of June 10th, 2002) has been transposed

in Italy

FOOD SUPPLEMENTSFOOD SUPPLEMENTS

products capable of performing

nutritional effects physiological effects

Prof. Roberto Verna

FOOD SUPPLEMENTS:FOOD SUPPLEMENTS:(46/2002/CE 6(46/2002/CE 6--1010--2002)2002)

in particular, but not limited to, vitamins, minerals,

capsules, tablets, bars, vials, bags

in particular, but not limited to, vitamins, minerals,

amino acids, fatty acids, fibers and herbal extracts

Prof. Roberto Verna

Guidelines on foods intended to meet

intense muscular effort, especially for sportsmen

Products aimed at energy integration

Products with minerals designed to restore salt and

water losses (...)water losses (...)

Products for the integration of proteins

Products for the integration of amino acids and

derivatives (creatine)

Other products with nutritional value, adapted to an

intensive muscular effort

Combination of the above products

Prof. Roberto Verna

VITAMINS AND MINERAL SUPPLEMENTS

Supplementation of vitamins in the diet, in most cases, is

incongruous and unnecessary

Minerals replenish salt and water losses resulting from

physical activity

incongruous and unnecessary

Sportsmen seldom have a vitamin deficiency

Moreover, if vitamins are “good”, it doesn’t

mean they can’t become “bad” if abused

Prof. Roberto Verna

Even among sportsmen the culture of “natural

supplement” is becoming more widespread

The erroneous belief that, being natural, must necessarily be

harmless

The effect of word of mouth propagation, especially in clubs

HERBAL PRODUCTS

The effect of word of mouth propagation, especially in clubs

and gyms

Advertising campaigns not subject to controls

The wide availability on parallel sales channels (internet)

self-medication w/out supervision

Prof. Roberto Verna

A scientific demonstration of effectiveness

Correct information of the action on the body and

on the performance

Certainty of the content of products

Is the use of supplements “safe”?

ARE MISSINGARE MISSINGARE MISSINGARE MISSING

- Health risks

- Commercial fraud

- Positivity to antidoping tests

Prof. Roberto Verna

Incongruous / Hazardous

use of supplements and health products

Raw materials and production processes are not

always controlled.

Extreme vagueness in the indication of the dosages.Extreme vagueness in the indication of the dosages.

Lack of references to age, sex, body weight, in place to

pathological situations (hypertension)

Belief that the dosages are not critical as for medicines.

There isn’t any real assessment of the effectiveness and toxicity

of such products

Prof. Roberto Verna

Presence of pharmacologically active

molecules that have names quite often

misleading:

Incongruous / dangerous use of

supplements and health products

misleading:

ma-huang, guarana, pullulan, etc. ...

Different composition versus the one

shown on the label(contamination, whether deliberate or accidental)

Prof. Roberto Verna

“ETERNAL LIFE” (slimming)

Dictamnus dasycarpus plant contains numerous toxins

3 cases of liver failure, 1 death

Incongruous/hazardous use ofsupplements and health products.

“JIN BU HUAN ” (sedative, analgesic)

Lycopodium serratum plant containing

a morphin-like alkaloid

7 cases of hepatotoxicity and acute liver failure

Prof. Roberto Verna

Different composition from the one declared on

the label (contamination, whether deliberate or

accidental, with doping substances or their

precursors)

Potential risk of

positive drug test

precursors)

Active ingredients contained in herbal products

marked with an “unusual” name (eg, ephedrine

/ ma huang-...)

Unknown interactions with other drugs /

metabolites and / or endogenous substances

Prof. Roberto Verna

� Product based on a mixture of herbs, free for

� Declared ingredients: Cola nut, Passiflora, Ma-

Potential risks of a positive doping

test: an example...

� Declared ingredients: Cola nut, Passiflora, Ma-

huang, Siberian Ginseng, Chinese Dandelion,

Ginger, Seaweed, Pullulan, Gymnema sylvestre

� The analysis showed the presence of ephedrine

(ephedrine, methylephedrine).

Prof. Roberto Verna

The presence of anabolic steroids was found in

some packages of food supplements

in individual packages, NOT all

Potential risks of a positive doping test:

a further example...

The contaminated products are often of U.S. production, almost

always not available over the counter, but on safe parallel channels

particularly Internet

Contaminated capsules contained steroids

in amount ranging from 0.3 to 500 micrograms

in individual packages, NOT all

the capsules were contaminated

Prof. Roberto Verna

Supplements and herbal products

should be considered as drugs?

YES, YES, accordingaccording toto WHOWHO

Editorial in JAMA, March 26th, 2003: supplements

should be considered in all respects and consequently

medication should be adequate evidence available on

their validity.

Prof. Roberto Verna

It has been proposed the use of a mark

(Green Seal?)

to be applied to these products,

with the indication of:

ABSENCE OF SUBSTANCES

PROHIBITED FOR DOPING

Prof. Roberto Verna

The administration of medications,

including supplements, to people

without disease, as in the case of

athletes, is always dangerous because

there is no therapeutic need, that is thethere is no therapeutic need, that is the

main purpose of a medication.

Prof. Roberto Verna

The excessive "medicalization",

represents a serious danger for the athlete,

NOT ONLY FOR THE POSSIBILITY OF A

POSITIVITY TO DOPING TESTS,

BUT ALSOBUT ALSO

FOR THE POSSIBLE OCCURRENCE OF

ADR: �� Adverse Drug Reaction

Prof. Roberto Verna

The ADRs in the U.S. (JAMA 1998; 279: 1200-05)

are, incidentally, the fourth leading cause of death

after cardiovascular diseases, cancer and stroke:

more than 100,000 deaths / year.more than 100,000 deaths / year.

The data comes from a meta-analysis of 39 prospective

studies in hospitalized patients:

��2.216.000 2.216.000 patients with serious non-fatal ADRs

�� 106.000 106.000 patients with fatal ADRs

Prof. Roberto Verna

DoubtsDoubts ofof Sport MedicineSport Medicine

Can the sports physician, motivated by the need for prevention

(no disease) administer drugs without violating the law and

professional ethics?

The physician of professional societies should make a note of

the use of supplements/health products

TUE: Therapeutical Use Exemption

Prof. Roberto Verna

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