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 99klinik@ursula-jacob.de

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 klinik@ursula-jacob.deFax: +49 (0) 7443 – 964 24 – 99 www.ursula-jacob.de