freitag, 27. märz 2015 dr. ursula jacob medical director usa 2012
TRANSCRIPT
Freitag, 21. April 2023
Dr. Ursula JacobMedical director
USA 2012
ClinicDr. Ursula Jacob Silberwaldstrasse 34
D 72280 Dornstetten – Hallwangen GermanyTel: +49 7443 964 240
Fax.: +49 7443 964 24 [email protected]
Company Overview
• The clinic has 17 rooms
• Over 7,000 patients treated, from Europe, Australia and North America.
• Staff of 4 doctors,12 nurses
Indications
• preventive diagnostics and treatments • regenerative treatments• oncological diseases• hematological diseases• metabolic disorders• chronic neurological diseases• chronic viral diseases
Diagnostics
• Electrocardiogram (at rest and stress)
• Sonography
• Pulmonary function test
• Bone marrow cytology with rapid diagnostic
• Biopsy under appropriate control
Diagnostics• Diagnostics in cooperation:• X-Ray• CT and MRT• Bronchoscopy• Gastroscopy• Colonoscopy• Rectoscopy• PET (positron-emission-tomography)• Scintigraphy• Laboratory diagnostics (standard diagnostics, tumour
markers, immunology)• Chemosensitivity test• CTC Test (Circulating Tumour Cells)• CFS Test (Chronic Fatigue Syndrome)• Pathology• Genetic testing
Therapies
• Hyperthermia• Immunological therapy• Naturopathy• Psycho-oncological treatment• Nutritional therapy• Photopheresis• Individual chemotherapy / Immune therapies• Regenerative therapy• Antiviral therapy• Individual preventative treatments• Various vaccination therapies
History of Cell Therapy• Rufus von Ephesus 98-117 Detection of the human thymus gland• Galen 130-200 Exact description of the thymus• Vesalius 1543 Pictorial illustration of the thymus• Felix Platter 1536-1614 First clinical correlation „thymus death“• Sir Astley Cooper 1832 A thymus tumor is first described• Restelli 1845 Animal trials• Friedleben 1858 Thymectomy• Emil T. Kocher 1883 „Transplantation“ (1841-1919)• J. Wagner-Jaureg, G. Bayer (Hrsg.)
1913 Textbook on Organotherapy
• Elis Sandberg (THX) 1938 Publication of theoretical studies• Aleksandrowicz • Miller• Neymeyer• Pesic• Skotnicki (THF)
Stem cells
1. Adult stem cells
2. Umbilical stem cells
3. Fetal stem cells
4. Early embryonic stem
cells
Source: Claustres M et al., Horm Res. 1988; 29: 17-22
Stem cells – Differentiation
Source: Claustres M et al., Horm Res. 1988; 29: 17-22
Stem cells - Type
Stem cell type Source TissueEmbryonal Embryo All cells
Hematopoietic Bone marrow
Cord blood
Blood cells
Brain cells
EndotheliumNeuronal Fetal brain
Cord blood
Glial cells
Blood cells
Mesenchymal Bone marrow
Cord bloodMuscle, liver, bones, cartilage, endothelium
Source: Data on file
Stem cells – Characteristics (I)Molecule
Function Typically Expressed on Comments
CD2 Ligand of CD58(LFA-1)
Thymocytes NK-cells,T-cells
Lineage marker
CD14 LPS-R Monocytes, macrophages Lineage marker
CD19 B-cells, pre-B-cells Lineage marker
CD54 ICAM-1 adhesion molecule, binds LFA-1 (CD11a)
Antigen-presenting cells Lineage marker
CD64 FC-y Receptor I Monocytes, macrophages Lineage marker
CD94 NK-cells Lineage marker
CD34Bone-marrow derivedhematopoietic stem cells (HSC)
Key marker hematopoietic stem cells
Source: Data on file
Stem cells – Characteristics (II)Molecule
Function Typically Expressed on Comments
CD38Pre-B-cells, plasma cells thymocytes, dendritic cells, macrophages
Absent on HSC
CD45 Tyrosine kinase Leukocyte common antigen Lineage marker
CD71Transferrin R, activation marker
Activated and most dividing cells
CD117C-kit, stem cell factorReceptor (SCF-R)
Hematopoietic stem cells (HSC),hematopoietic progenitor cellsmesenchymal stem cells (MSC)
CD123 IL-3R Hematopoietic stem cells
Source: Data on file
Stem cells – Characteristics (III) Molecule
Function Typically Expressed on Comments
CD133
Early hematopoietic stem cells (HSC), neuronal stem cells, glial stem cells
Progenitor marker
CD243Multi drug resistance R (MDR-1)
Liver cells, gastrointestinal tract endothelial, brain, adrenal gland
Early pluripotent stem cells
Ki-67 Proliferation Proliferating G1 and S phaseAlkalinephospha-tase
Granulocytes, osteoblasts, mesenchymal stem cells, embryonal stem cells
Source: Data on file
Stem cells - Stage
Source: Data on file
Stem cells - Stage
Source: Data on file
Stem cells - Stage
Source: Data on file
Stem cells - Stage
Source: Data on file
Stem cells - Undifferentiated
Source: Data on file
Stem cells - Therapy
Source: Data on file
Stem cells - Isolates
Abb No 12
Fresh Sample
Culture 7dwithout growth factors
Culture 7dwith growth factorswith /without serum
Source: Data on file
Stem cells - IsolatesCulture 7d Minus/Plus Essential Growth Factors
Source: Data on file
Patient Case History
Patient: male, dob: 1957-06-30
Diagnosis: Secondary Immune Deficiency Syndrome (since birth)
(IgM deficiency), (FS Syndrome)
Recurrent zoster infections, (genital, abdominal, face)
Exacerbating since 1999 (3-4 attacks per year)
Increasingly impaired concentration (since 2000)
Increasing fatigue (since 2000)
12/1999: (PNP) Peripheral Polyneuropathy of legs
Arthrosis of left shoulder joint
Source: Data on file
Patient Case History/Diagnostics
Lab resultsJan. 2000EBV-IgG: 112HSV-IgG: 1:82000IgM: 29 mg/dl
Nov. 2000EBV-IgG: 80HSV-IgG: 1:20000IgM: 35 mg/dl
Oct. 2001EBV: 116HSV: 1:24000VIgM: 19 mg/dlCMV-IgG: 1:590(for the first time positive)
Dec. 2002EBV-IgG: 134HSV: 1:56000IgM: 26 mg/dlCMV: 1:230 (normal)
May 2006:EBV-IgG: 166HSV-1gG: 1:32000CMV: neg. IgM: 21 mg/dl
Source: Data on file
Patient Case History/Therapy
Since 1999:Administration of immune globulin
Immune therapy with ▪ Thymus extract ▪ Photopheresis Regenerative therapy with growth factors for ▪ Brain ▪ Nerves ▪ BonesAdministation of umbilical cord stem cells 2004
Result:
1) Improved lab results
2) Improved concentration and stamina
3) Fewer infections and zoster attacks
Source: Data on file
Patient Case History/Results Brain PET: Comparison 07/04 vs 10/05Reduction of glucose consumption in % related to the max. activity of the cerebral cortex (=100%)
Region Right% of max. activity
Left% of max. activity
G. orbitales 75 70G. front. sup. 75 75G. cinguli 80 80G. praecentr. 70 70G. postcentr. 75 75Lob. parietalis inf. 80Lob. parietalis. sup. 75 75G. temp. inf. 70 75G. temp. med. 80 75G. temp. sup. 80 80G. occipito-temp. lat. 70 75Cerebellum 70 75
Thalamusmoderate reduction in comparing sides
Nucl. lentif. minor reduction in comparing sidesSource: Data on file (Report Dr. Hörr, 31.10.2005)
Patient Case History/Summary
▪ In comparison with a normal collective (n21) the glucose absorption is reduced by a moderately diffuse rate. A region in the white substance left front is also accentuated. ▪ The maximum glucose absorption of the cortex is reduced with its almost 20 umol/100 g and lies moderately below the standard range of 30 (+/- 5) umol/min/100 g brain tissue as as determined at the Clinic. ▪ Accentuated by nature are the changes described in the chart, in particular in the cerebellum, the ventral polar segments of the temporal lobe, occipitotemporal and high parietal. ▪ In comparison with the previous examination of 19.07.2004 a drastic improvement of the general metabolism to almost twice the glucose consumption is revealed.▪ The inhomogeneities in particular in the cerebellar and occipitotemporal segment appear to be by far lower than in the previous examination.
Source: Data on file
T.W.m. 2004 13umol
T.W.m. 2005 20umol
CFScurrent diagnosis and therapies
Compendium Prof. Dr. Bieger Germany presented by Dr. Ursula Jacob
Neuroendokrine Störungen-Tabelle.Bild-2005
CFS
CFS
CFSOver 80% post-infective
Ca. 20% idiopathic
NeurodysregulationFatigueFibromyalgiaDepressionInsomniaCognitionIBS
FatigueSubf. temperatureRec. HerpesT-cell defectNOx
Inflammation
Immune defect
Pattern of change in individual symptom factors in participants with (orange) and without (white) post-infective fatigue syndrome.
I Hickie et al: BMJ. 2006 333(7568): 575-
Post-infective and chronic fatigue syndromes precipitated by viral and non-viral pathogens: prospective cohort study
CFS.Fatigue.Postinfectious-BMJ.08.06
ReportMale, 23 J.
D830-0808, 11.11.05 Diagnosis: Chronic Fatigue
EBV-Reactivation
B06 x 2 atypEBV-Serologie.Hämochromatose.11.05
Positive staining of B lymphocytes with monoclonal antibodies against EBV antigens EA (A), BZLF1 (B), and VCA (C) by immunostaining with the APAAP technique (original magnification × 1,000).
Lytic Replication of Epstein-Barr Virus in the Peripheral Blood: Analysis of Viral Gene Expression in B Lymphocytes During Infectious Mononucleosis and in the Normal
Carrier State
NS Prang et al: Blood, 89: 1997: pp. 1665-1677EBV.Infektion.aktiv.Antigennachweis-Prang.1997
NK-cell Activity-CFS-Patients.ppt
NK-Cell Activity in Different Patient Groups
Quelle: IMMUNOSCIENCE LABORATORY INC.
NK-
CELL
ACT
IVIT
Y (L
YTIC
UN
ITS)
NK-
CELL
ACT
IVIT
Y (L
YTIC
UN
ITS)
80
70
60
50
40
30
20
10
0SOLDIERSCONTROL
CIVILIANCONTROL
CFSPATIENTS
TOXICCHEMICALEXPOSURE
ALCOHOLINTOXICATION
CANCERPATIENTS
78±21 units
41±19units
13±6units 10±8
units8±9units 6±5
units
Neuroendokrine Störungen-Tabelle.Bild-2005
Neuro-endocrineImmun-
Dysfunction
MCS
Restlesslegs
PTSDParkinson
FMSFibromyalgia
Irritable Colon
Depression
ADS/ADHS
Adiposity
Insomnia
Burn-Out
CFS
PMSMenopause
Migraine
Fibromyalgie.Bildserie.2005
Chronic Fatigue Syndrome, Fibromyalgia, and Multiple Chemical Sensitivities in a Community-Based Sample of Persons With Chronic Fatigue Syndrome-Like Symptoms
Psychosomatic Medicine 62:655-663 (2000)
Frequency and Percentage of Coexisting Diagnoses for Each Fatigue Status Group.( ) estimates of previous literature reports.ICF = idiopathic chronic fatigue not meeting full CDS criteria. CFexplained = patients with fatigue due to psychiatric or other medical condition.
CFS ICF CFexplained no Fatigue
MCS 40,6 % 46,7 % 43,8 17 %
FM 15,6 %(20 – 70%)
4,4 % 6,7 % 0 %
MCS + FM 3,1 % 6,7 % 5,6 % O %
Occurence of complications in (%) by CFS or in combination CFS with FMS and MCS (Ciccione, 2003)
Comparison of the prevalence of abnormal LBT in controls and subjects with IBS and fibromyalgia
A link between irritable bowel syndrome and fibromyalgia may be related to findings on lactulose breath testing
Annals of the Rheumatic Diseases 2004;63:450-452
Conclusions: An abnormal lactulose breath test is more common in fibromyalgia than IBS. In contrast with IBS, the degree of abnormality on breath test is greater in subjects with fibromyalgia and correlates with somatic pain.
Fibromyalgie.Bildserie.2005
Stressor - Exposition
hypothalamicactivation
blockedNeuroregulation
Modulation caused by :
environmental factors / harmful substances, over-training, infectionsEBV/HHV6-Reactivation
ACTH, Substance PHGHC
Dopamine NoradrenalineGABA Glutamate
fatigue, depressionpain, cognitionappetite, cravingsleep, motivationaggression, fearchemical intolerance
InflammationCytokine activation
Virus reactivation, InfectionT-cell activation, INK-cell defect
Serotonin
Modulation caused by:
earlier traumatic eventsneuroplasticity, genetic factors,allergy, inflammation
Cortisol
Stress.CFS.Stressorexposition.Schema
efferentHyposensitivity
CRH
• CONSUMERS CONCERN ABOUT STRESS & ANXIETYGREAT BRITAIN 44 % GERMANY 41 %FRANCE 42 % USA 48 %JAPAN 62%
Source: Leatherhead Food RA, Health Focus
• 10-15% OF THE POPULATION SUFFER FROM ANXIETY ILLNESS
• STRESS AT WORK : A VERY COMMON PROBLEM- a very high cost in terms of workers’ health- absenteeism & lower performance
Cost of work-related stress/year: $200 billion worldwideSource: International Labour Office
-> European Union : € 20 billion - 40 million workers affected-> United Kingdom : 40 million workdays lost annually-> United States : $ 60 billion - 550 million workdays lost annuallySource: Guidance on work-related stress/European Commission/Spice of live or kiss of death
Stress-related disorders affect nearly 400 million people worldwideSource: WHO-2000
Worldwide Stress
Stress in Deutschland.International-2004
ScienceDaily. Retrieved February 19, 2008,
Night-time noise from aircraft or traffic can increase a person's blood pressure even if it does not wake them, according to a new study published in the European Heart Journal. Scientists from Imperial College London and other European institutions monitored 140 sleeping volunteers in their homes near London Heathrow and three other major European airports
Aircraft noise events caused an average increase in systolic blood pressure of 6.2 mmHg and an average increase in diastolic blood pressure of 7.4 mmHg. Similar increases in blood pressure were seen also for other noise sources such as road traffic
Stress.Fluglärm.Blutdruck.Schlaf-SD.02.08
Aircraft Noise Raises Blood Pressure Even While People Are Sleeping, Says Study
Wilbert-Lampen U et al. N Engl J Med 2008;358:475-483
The FIFA World Cup 2006 in Germany started on June 9, 2006, and ended on July 9, 2006. The 2006 World Cup matches with German participation are indicated by numbers 1 through 7: match 1, Germany versus Costa Rica; match 2, Germany versus Poland; match 3, Germany versus Ecuador; match 4, Germany versus Sweden; match 5, Germany versus Argentina; match 6, Germany versus Italy; and match 7, Germany versus Portugal (for third-place standing). Match 8 was the final match, Italy versus France
Cardiovascular Events during World Cup Soccer
Daily Cardiovascular Events in the Study Population from May 1 to July 31 in 2003, 2005, and 2006.
Stress.FußballWM.KHK.Herzinfarkte-NEJM.01.08
NEURO-REGULATION I
Stress hormone axisHPT – AP – ADR
Catecholamine – Serotonin – ANS-axis
Major components of Major components of the central and the central and
peripheral stress systemperipheral stress system
Stress Resonse System-Scheme.ppt GP Chrousos J Allergy Clin Immunol 2000, 106:S275-91
Locus ceruleus
Noradrenergic systemNoradrenaline
Arcuatenucleaus
Paraventricularnucleus
Sympathetic ganglion
Dorsal root ganglion
CRHAVP
POMCPeptides
Cortisol
ACTH
AdrenalineNoradrenaline
Pituitary
NoradrenalineNeuropeptides
Stress systemCholinergic*Serotonergic*GABA/BZD-
POMC peptides- The hypothalamic CRH and central noradrenergic neurons mutually innervate and activate each other, although they exert presynaptic autoinhibition through collateral fibers. AVP from the paraventricular nucleus synergizes with CRH on stimulating ACTH secretion. The cholinergic and serotonergic neurotransmitter systems stimulate both components of the central stress system, although the gamma aminobutyric acid / benzo-diazepine (GABA/BZD) and arcuate nucleus proopiomelanocortin (POMC) peptide system inhibit it. The latter is directly activated by the stress system and is important in the enhancement of the analgesia that takes place during stress.
SALIVA CORTISOL IN RELATION TO HIGH AND LOW STRESSSALIVA CORTISOL IN RELATION TO HIGH AND LOW STRESS
Stress Saliva Cortisol.ppt.ppt P Björntorp , R Rosmond: Obesity and Cortisol : Nutrition 16: 924-936, 2000
Morning Lunch Bedtime
15
10
5
0
Saliv
ary
Corti
sol (
ng/m
l)
NormalLow StressHigh StressBurn-OutInverted pattern
Stress.Burnout-Cortisol.Saliva-Kurven
B07 NeuroStress.endDepression.Hypercortisolismus.Therapierefraktär
Result:Result: 803-0730 Female 60 J., 31.01.07
Diagnosis Endogenous depressionRefractory to therapy– numerous antidepressants without success – significant weight gain, fear, hot flashes, fatigue, elevated blood pressure
Hypercortisolism !
2650226.pptB08 Burnut.NNR-Schwäche.Frgl. HVL-Insuffizienz
Result:Result: 265-0226, 01.02.2008 Female 47 J.
DiagnosisDiagnosis BurnOutBurnOutHyperthyroidism, maybe Hyperthyroidism, maybe anterior pituitary deficiencyanterior pituitary deficiency
DiagnosticNeuroStress ProfileADR-Steroid extremely low (ACTH low); NT normal
Total Burn-Out !
ACTH, plasma cortisol and salivary cortisol responses in CFS patients over time
ACTH, plasma cortisol and salivary cortisol responses over time and integrated endocrine responses (inserted bar graphs) of ACTH, plasma cortisol and salivary cortisol responses over time and integrated endocrine responses (inserted bar graphs) of CFS patients (CFS patients ( or black) and healthy controls (• or gray) in the TSST or black) and healthy controls (• or gray) in the TSST
J Gaab et al: Psychoneuroendocrinology (2005) 30:188-198
CortisolSaliva
CortisolPlasmaACTH
CFS.Stresshormonachse.Inflammation-2005
Saliva Cortisol
120
100
80
60
40
20
0CFS CFS
with psych.comorbidity
Controls
Corti
sol (
nmol
/ 24
h ur
ine)
CFS.Cortisol.24hUrin-01.07
24h urinary cortisol in CFS with and without mental alteration (depression)
CFS
Stress
Chronic Stress
Burn-OutHypocortisolism
Depression
Hypercortisolism
NeuroStress
Stress.akut.chron.Schema-04.06
Rapid activation of the HPT-AP-ADR-axis, Cortisol-Noradrenaline/Serotonin increase
Chronic hyperactivity of the HPT-AP-ADR-axis, elevated Sympathic tone, genetic disposition
Acute Stress
CRH-period stimulationCRH-insensitivity
FatigueHypocortisolism
5HT-Deficit
NEURO-REGULATION II
HPT – AP – ADR Stress hormone axis
CNS-ANS-axisCatecholamine – Serotonin
GABA - Glutamate
Neurotransmitter
• Neurotransmitters are the chemicals within the vesicles that synaptically separated neurons utilize for chemical communication
The impact of neurotransmitters
GABAGABAGLUTAMATGLUTAMAT
Noradrenaline Serotonin
Dopamine
anxietycrankiness
cognitive function
disposition
appetitesex
aggressionmotivation
happinesspower
Ergotropicsympathetic guided potency
Trophotropicdrive
Neurotransmitter-Wirkprofile x 2 –04.06
CMIChronic Multisystem Illnesses
Serotonin is reduced in about 45 % of FMS-patients Increased dopamine sensitivitySubstance P, neuro-peptides high
FMS FMS Fibromyalgia Fibromyalgia
CFSCFSChronic Fatigue Chronic Fatigue
SyndromeSyndrome
MCSMCSMultiple ChemicalMultiple Chemical
SensitivitySensitivity
Serotonin is low in > 80 % of CFS-patientsHypocortisolismDHEA/S low
Serotonin is low in > 70 % of MCS-patientsLatent hypocortisolismSubstance P elevation/neuroinflammation ?
Possible causes of neurotransmitter troubles
• stress
• unbalanced diet
• ambient toxins
• genetic factors
• illness (Inflammation)
Serotonin.Tryptophan.Lebensmittel.Bildserie.04.08
Some tryptophan-rich foods as example for 100 Gram:
Lactalbumin6900 mg
Whey protein
2100 mg Egg
1800 mg
Nuts 1000-1800 mg
Pears 1400 mg
Potatoes
1400 mg Cheese
1400 mg
Onions 1400 mg
bananas, curd, cheese, salmon, turkey, duck, avocado, potatoes
Tryptophan
Tryptophan MetabolismTryptophan Metabolism
Tryptophan
Kynurenine
Quinolinic acid
Picolinic acid
Serotonin
TDO IDOImmune cellNerve cellEndothelial cell
IFN (IL-12), TNF/PGE2,
Liver, kidneysastrocytes
5%
Neurotoxicity
iNOS, NMDA/Glutamate-Agonists
MelatoninBupropion (Zyban, Wellbutrin)SSRI‘sAntioxidantsCoxib (iCOX2)Boswellia
Kynurenic acid
iNOS, NMDA/AchR-Antagonist
Neuroprotection
Tryptophan Stress/CortisolProlactin 95%
SSRI‘sAntioxidantsCoxib (iCOX2)
DOPA -Decarboxylase
Tetrahydrobiopterin Folic acid
Tryptophan
5-HTP5-Hydroxytryptophan
Vit B6
Serotonin
Tph 2Tryptophan-Hydroxylase
5HTTP5HT-Transporter
MAOMonoaminoxidase
5HTA1,25HT-Receptor
Genetic!
Accuracy Gene SNP
76,3 %Tph2, NR3C11, NRC1, NR3C12 CRH2
rs1386486, rs1866388, rs6169, rs6188, rs2284217
75,2 % Tph2, NRC1, NR3C12, CRH2 rs1386486, rs6169, rs6188, rs2284217
„Tph2, COMT, NRC1, NR3C12 CRH2
rs1386486, rs4633, rs6169, rs6188, rs2284217
„Tph2, Tph22, NR3C11, NRC1 CRH2
rs1386486, rs4760750, rs6169, rs6188, rs2284217
CFS. Candidate genes-neurohormoal axis.2006 BN Goertzel et al. Pharmacogenomics (2006) 7: 475-83
Combinations of SNPs in neuroendocrine effector and receptor genes predict CFS
The top three genes containing SNPs accounting for the highest accumulated importance were Tph2 (neuronal tryptophan hydroxylase), COMT (catechol-O-methyltransferase, and NR3C1 (nuclear receptor subfamily 3, group C, member 1 glucocorticoid receptor.
Serotonin - Biosynthese.ppt
Folic acid
Tryptophan
5-HTP5-Hydroxytryptophan
Vit B6
Tryptophan-Hydroxylase
Serotonin5-HAT/5-Hydroxytryptamine
Melatonin
Kynurenine
N-Acetylserotonin
IDO Indolamine-2,3-Dioxigenase
-Interferon
5-HIES5-Hydroxyindol- acetic acid
Up to 95%
1-10%
Nicotinic acidVit B3
NAD/NADH
> 90%
Proteinsynthesis
5-90%
*very low levels of B-6required so when B-6 is lowthis step goes first resulting
in increased amounts ofxanthurenic acid
Inflammation !
STRESS
INFLAMMATION
Cytokine characteristics in CMICytokine characteristics in CMI
Zytokincharakteristika bei CMI
MCSMCS CFSCFSFMFM TNF-α (-) +IL-1 (-) + ++IL-6 + +IL-8 ++ ++ IL-2 (+) IFN-gamma +++ -/+IL-10 +(+) - -
Patarca R: Cytokines and Chronic Fatigue Syndrome. Ann N.Y Acad Sci 2002: 185-200Wallace DJ et al: Cytokines play an aetiopathogenetic role in fibromyalgia: a hypothesis and pilot study. Rheumatology 40: 743-749, 2001Mayer WR, Bartram F, Bieger WP: MCS- Eine chronische Entzündung? Z Umweltmedizin 10: 88 – 96, 2002
CMI = Chronic Multisystem Illness
anorexia increased appetitenausea agitationfatigue/exhaustion emotioninsomnia added sleeppain analgesia headache, migraine no painsubfebrile temperature no fevermetabolic activation metabolic activation
(catecholamine, CRF), normalising (glucocorticoid inhibition)
inflammatory reaction relaxed acute phase reactionIL-1, IFN-gamma, TNF-alpha, PGE2
Sickness-Stressreaktion.ppt
Abnormal stress Normal reaction stress reaction
Oxidants,harmful substances
CytokinesIL1, IL6, TNFa
ROS
NFB
IB
UV-lightrays
Gene-activating
Virusesand germs
Acute StressNoradrenaline
NFATAP-1
5-LOX
InflammationInflammation
CytokinesIL1IL8, TNF IL6
Arachidonic AcidPhospholipase A2
ROS
COX2
COX1
iNOS
ONOO•
Chronic StressAdrenaline
Nitric Oxide Synthesis
Arginine + O2 NO + Citrulline
NO2
+ NO3
NOS
eNOSnNOSmtNOSiNOS
Arginine succinate
Der mitochondriale Energiestoffwechsel besteht aus Pyruvatoxidation (PDHC), ß-Oxidation der Fettsäuren, Zitratzyklus und vor allem der oxidativen Phosphorylierung. Gebildete Redoxäquivalente (NADH, FADH2) werden in der Atmungskette mit molekularem Sauerstoff (O2) zu Wasser umgesetzt. Dabei freigesetzte Energie wird vom Komplex V zur Synthese des universellen Energieträgers Adenosintriphosphat (ATP) verwendet. So werden in den Mitochondrien über 90% des Energiebedarfs des Körpers bereit gestellt.
Mitochondria are the fountain of energy for the body
Mirochondrien.Enerhgiestoffwechsel.2005
BE Neurostress.KKT.Atlas. BHS.S100.NoTyrosin.2005
Result Female, 57 J. VS D830 0668 25.7.2005
2-2Treatment: Fresh cell extracts (adrenal),Micronutrients including:OPC, carnitine, alpha-lipoic acid, curcumin, omega-3
Diagnosis: Whiplash injuryFatigueEBV-reactivation, Anxiety disorder
BE Neurostress.KKT.Atlas. BHS.S100.NoTyrosin.2005
Page 2Treatments: Fresh cell extract (adrenal/thymus) Micronutrients including:OPC, carnitine, alpha-lipoic acid, curcumin, omega-3
S-100 18,6NSE 33
FATIGUE – DIAGNOSTICI. NeuroStress Cortisol 8, 12, 20 hrs; DHEAS 8, 20 hrs Catecholamine (Adrenaline, Noradrenaline, Dopamine), Serotonin,GABA, Glutamat e Glycine, Taurine, Glutamine, TSH, ACTH, ProlactinII. Inflammation CRPs, NF-kB, MPO Cytokine (IL-6, IL-1ß; TNF-alpha, sIL2R, IFN-gamma)
ITT® Immuntoleranztest (IL 2, IL 10, INF-,TNF-)
III. Neuro-inflammation S-100, NSE, alpha-Crystalline Nitrotyrosine, Citrulline
III. Micronutrient Glutathione cellulär, CoQ10, Homocysteine (B12, Folate), Vitamin B6 Zinc, Selenium, Ferritin, Magnesium, Vitamin D
CMI.CFS.FMS-Diagnsotik.Therapie.Schema-06.08
CFS – diagnostic ladderGrade I Cortisol 8, 12, 20 hrs; DHEAS 8, 20 hrs Catecholamine (Adrenaline, Noradrenaline, Dopamine) Serotonin,GABA, Glutamate
Grade IIITT©, EBV (RNA/DNA), Borrelia-AbNF-kB, Cytokine: CRPs, TNF,IFN GSH, Hocy, Vit B6, Q10, Vit D, TSH, Ferritin
Grade IV Nitrotyrosine, S-100, Zn (E), Se (E), Mg (E)ACTH, Prolactin, TestosteroneImmune status
Grade IIIHHV6 (DNA), CMV-Ab,NK-CheckANA, IgG, IgA, IgM, IgE
CMI.CFS.FMS-Diagnsotik.Therapie.Schema-06.08
Pivotal neurotransmitter concept
Inhibition
AS-Therapie.Inhib.Excit-Konzept-04.06
(GABA, Serotonin, Glycine, Theanine)
Rearrangement of the balance between
Excitation
(Adrenaline, Noradrenaline, Glutamate, Histamine)
Amino acid - Support
• Amino acids/Neurotransmitters• Tyrosine (N-Acetyl-Tyrosine, Phenylalanine)• 5-HTP (Tryptophan), Glycine, Glutamine,• Mucuna (DOPA)
• Modulators• Taurine, Theanine, NAC, EGCG, Rhodiola
• Cofactors• Vit C, Vit B6, Folic acid, Vit B12, Selenium, Calcium,• Magnesium, SAMe, Cysteine, Tocotrienol
5-HTP
• Immediate Serotonin-precursor
• No regulatory feedback-inhibition (Tph 2)
• Well absorbed in the intestinal tract
• Free passage through the blood brain barrier
• Dose-constrained serotonin elevation
• Boosts stress hormone axis (Cortisol)
• No immunsuppression (Trp Kynurenin building)
• No neurotoxicity (Trp Chinolinic acid)
• Dosage: 50-800 mg / day
NeuroStress.AS-Therapie.Wirkstoffe x 35-09.06
GABA (Gamma Aminobutyric acid)
GABA-Rezeptor.Regulation.Schemata-2007
TaurineGABA-receptor modulation ++Neuroprotective, blocks Glutamate toxicity
GlutamineGABA-synthesis5-HT(P)
stimulation of GABA-activity5-HT is necessary for GABA function
Theanineincrease GABA effectpromote GABA synthesis
RhodiolaExcitatory in low doses, inhibitory in high doses
Progesteroneincrease GABA-effect ++Neuroprotective (allo-Pregnanolone)
BarbituratepromoteGABA-effect
Melatoninincrease GABA-binding
BenzodiazepineLocked on GABA-Receptor, high affinity
FATIGUE -THERAPY
Level IIndiv. micronutrients 5-HTP 100 mgTaurine 150 mgTheanine 50 mgNAC 110 mgplus: Vit B6, B12, Vit C, Folic acid, Mg, Zn, Se
Level IIIndiv. micronutrients5-HTP 200 mgTyrosine 1200 mgNAC 200 mgTheanine 136 mgplus: Vit B6, Vit C, Folic acid, Calcium
OrIndiv. micronutrients5-HTP 50 mgTyrosine 50 mgGlutamine 350 mgTaurine 250 mgTheanine 75 mgplus: Vit B6, Vit C, Folic acid, Tocopherol, Mg
CMI.CFS.FMS-Diagnsotik.Therapie.Schema-06.08
• Melatonin is produced in darkness from Serotonin via N-Acetylserotonin in the pineal glad
• Neuronal Antioxidant – in reduced and in oxidised form• Potentiates GABA-Receptor building • Operates as sedative• Operates to promote sleep• Antagonist of Glutamate and Chinolinic acid (Trp-KYN-
Metabolite)• Operates as an anticonvulsant
Melatonin Neuroprotection
Patient: C.J. (04/13/44) m.
Diagnosis: CFS following drug abuse over 20 years, Osteopenia, Lack of concentration
Therapy:Fresh cell extracts ( thymus, cerebrum, gut ) Detox
Patient: C,J (04/13/44) m.
26.03.200827.10.2008
Patient: M.J. (12/11/62) f.
Diagnosis: Coma for 4 months following accidentMeningitis,Adrenal dysfunction
Therapy:Fresh cell extracts (brain, adrenal, gut, cartilage) Hormone balance
Patient: M,J (11.12.62)
05.11.2008 20.11.2007
Patient: M,J (11.12.62)
05.11.200822.09.2009
Patient: H.G. (01/08/64) m.
Diagnosis: HemochromatosisHeavy metal intoxicationDiabetes - Type II
Therapy:Fresh cell extracts (adrenal, pancreas, liver, thymus) Detox
Patient: H.G. (08/01/64) m.
19.09.2008
Patient: H.G. (08/01/64) m.
10.12.2009
Patient: H.G. (08/01/64) m.
17.03.2010
Patient: H.G. (08/01/64) m.
04.05.2010 17.03.2010
Patient: F-K.G. (09/03/39) f.
Diagnosis: Multiple Sclerosis,Irritable bowel syndromeCFS
Therapy:Fresh cell extracts (nerve, brain, gut, adrenal, thymus) Physiotherapy
Patient: F-K.G (09/03/39) f.
15.11.2007
Patient: F-K.G (09/03/39) f.
15.11.200709.01.2008
Patient: F-K.G (09/03/39) f.
09.01.200831.01.2008
Patient: F-K.G (09/03/39) f.
31.01.200831.07.2008
Patient: F-K.G (09/03/39) f.
09.01.2009 31.07.2008
Patient: G.U. (08/19/54) f.
Diagnosis: Heavy metal intoxicationCFSHormonal imbalance
Therapy:Fresh cell extracts (ovary, adrenal, thymus) Detox
Patient: G.U. (08/19/54) f.17.12.200705.06.2008
Patient: G.U. (08/19/54) f.01.12.200805.06.2008
Patient: G.U. (08/19/54) f.
01.12.200815.12.2009
I hope you didn’t fall asleep…Thank you very much for your kind attention!
Freitag, 21. April 2023
privat clinic Dr. Ursula JacobSilberwaldstraße 3472280 Dornstetten-Hallwangen
Tel.: +49 (0) 7443 – 964 24 – 0 [email protected]: +49 (0) 7443 – 964 24 – 99 www.ursula-jacob.de