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Dr. Ursula Jacob USA 2012 Medical director Samstag, 8. April 2017

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1 Dr. Ursula Jacob USA 2012 Medical director Samstag, 8. April 2017

2

3 Clinic Dr. Ursula Jacob Silberwaldstrasse 34 D Dornstetten – Hallwangen Germany Tel: Fax.:

4 Over 7,000 patients treated, from Europe, Australia and North America.
Company Overview The clinic has 17 rooms Over 7,000 patients treated, from Europe, Australia and North America. Staff of 4 doctors,12 nurses

5 Indications preventive diagnostics and treatments
regenerative treatments oncological diseases hematological diseases metabolic disorders chronic neurological diseases chronic viral diseases

6 Diagnostics Electrocardiogram (at rest and stress) Sonography
Pulmonary function test Bone marrow cytology with rapid diagnostic Biopsy under appropriate control

7 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

8 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

9

10 History of Cell Therapy
Rufus von Ephesus 98-117 Detection of the human thymus gland Galen Exact description of the thymus Vesalius 1543 Pictorial illustration of the thymus Felix Platter 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“ ( ) J. Wagner-Jaureg, G. Bayer (Hrsg.) 1913 Textbook on Organotherapy Elis Sandberg (THX) 1938 Publication of theoretical studies Aleksandrowicz Miller Neymeyer Pesic Skotnicki (THF)

11 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

12 Stem cells – Differentiation
Source: Claustres M et al., Horm Res. 1988; 29: 17-22

13 Stem cells - Type Stem cell type Source Tissue Embryonal Embryo
All cells Hematopoietic Bone marrow Cord blood Blood cells Brain cells Endothelium Neuronal Fetal brain Glial cells Mesenchymal Muscle, liver, bones, cartilage, endothelium Source: Data on file

14 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 CD19 B-cells, pre-B-cells CD54 ICAM-1 adhesion molecule, binds LFA-1 (CD11a) Antigen-presenting cells CD64 FC-y Receptor I CD94 NK-cells CD34 Bone-marrow derived hematopoietic stem cells (HSC) Key marker hematopoietic stem cells Source: Data on file

15 Stem cells – Characteristics (II)
Molecule Function Typically Expressed on Comments CD38 Pre-B-cells, plasma cells thymocytes, dendritic cells, macrophages Absent on HSC CD45 Tyrosine kinase Leukocyte common antigen Lineage marker CD71 Transferrin R, activation marker Activated and most dividing cells CD117 C-kit, stem cell factor Receptor (SCF-R) Hematopoietic stem cells (HSC), hematopoietic progenitor cells mesenchymal stem cells (MSC) CD123 IL-3R Hematopoietic stem cells Source: Data on file

16 Stem cells – Characteristics (III)
Molecule Function Typically Expressed on Comments CD133 Early hematopoietic stem cells (HSC), neuronal stem cells, glial stem cells Progenitor marker CD243 Multi drug resistance R (MDR-1) Liver cells, gastrointestinal tract endothelial, brain, adrenal gland Early pluripotent stem cells Ki-67 Proliferation Proliferating G1 and S phase Alkaline phospha-tase Granulocytes, osteoblasts, mesenchymal stem cells, embryonal stem cells Source: Data on file

17 Stem cells - Stage Source: Data on file

18 Stem cells - Stage Source: Data on file

19 Stem cells - Stage Source: Data on file

20 Stem cells - Stage Source: Data on file

21 Stem cells - Undifferentiated
Source: Data on file

22 Stem cells - Therapy Source: Data on file

23 Stem cells - Isolates Abb No 12 Fresh Sample Culture 7d
without growth factors with growth factors with /without serum Abb No 12 Source: Data on file

24 Culture 7d Minus/Plus Essential Growth Factors
Stem cells - Isolates Culture 7d Minus/Plus Essential Growth Factors Source: Data on file

25 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

26 Patient Case History/Diagnostics
Lab results Jan. 2000 EBV-IgG: 112 HSV-IgG: 1:82000 IgM: 29 mg/dl Nov. 2000 EBV-IgG: 80 HSV-IgG: 1:20000 IgM: 35 mg/dl Oct. 2001 EBV: 116 HSV: 1:24000 VIgM: 19 mg/dl CMV-IgG: 1:590 (for the first time positive) Dec. 2002 EBV-IgG: 134 HSV: 1:56000 IgM: 26 mg/dl CMV: 1:230 (normal) May 2006: EBV-IgG: 166 HSV-1gG: 1:32000 CMV: neg. IgM: 21 mg/dl Source: Data on file

27 Patient Case History/Therapy
Since 1999: Administration of immune globulin Immune therapy with ▪ Thymus extract ▪ Photopheresis Regenerative therapy with growth factors for ▪ Brain ▪ Nerves ▪ Bones Administation 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

28 Patient Case History/Results Brain PET: Comparison 07/04 vs 10/05 Reduction of glucose consumption in % related to the max. activity of the cerebral cortex (=100%) Region Right % of max. activity Left G. orbitales 75 70 G. front. sup. G. cinguli 80 G. praecentr. G. postcentr. Lob. parietalis inf. Lob. parietalis. sup. G. temp. inf. G. temp. med. G. temp. sup. G. occipito-temp. lat. Cerebellum Thalamus moderate reduction in comparing sides Nucl. lentif. minor reduction in comparing sides Source: Data on file (Report Dr. Hörr, )

29 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 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

30 T.W.m umol

31 T.W.m umol

32 CFS current diagnosis and therapies
Compendium Prof. Dr. Bieger Germany presented by Dr. Ursula Jacob

33 CFS Fatigue Subf. temperature Rec. Herpes CFS T-cell defect NOx
Over 80% post-infective Inflammation Immune defect CFS Neurodysregulation Fatigue Fibromyalgia Depression Insomnia Cognition IBS CFS Ca. 20% idiopathic Neuroendokrine Störungen-Tabelle.Bild-2005

34 Post-infective and chronic fatigue syndromes precipitated by viral and non-viral pathogens: prospective cohort study Pattern of change in individual symptom factors in participants with (orange) and without (white) post-infective fatigue syndrome. CFS.Fatigue.Postinfectious-BMJ.08.06 I Hickie et al: BMJ (7568): 575-

35 Diagnosis: Chronic Fatigue EBV-Reactivation
Report Male, 23 J. D , Diagnosis: Chronic Fatigue EBV-Reactivation B06 x 2 atypEBV-Serologie.Hämochromatose.11.05

36 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 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). EBV.Infektion.aktiv.Antigennachweis-Prang.1997 NS Prang et al: Blood, 89: 1997: pp

37 NK-Cell Activity in Different Patient Groups
NK-CELL ACTIVITY (LYTIC UNITS) 80 70 60 50 40 30 20 10 SOLDIERS CONTROL CIVILIAN CFS PATIENTS TOXIC CHEMICAL EXPOSURE ALCOHOL INTOXICATION CANCER 78±21 units 41±19 units 13±6 10±8 8±9 6±5 NK-cell Activity-CFS-Patients.ppt Quelle: IMMUNOSCIENCE LABORATORY INC.

38 Neuro- endocrine Immun- Dysfunction Depression Burn-Out CFS Irritable
FMS Fibromyalgia Burn-Out Neuro- endocrine Immun- Dysfunction CFS Irritable Colon MCS Insomnia Adiposity ADS/ ADHS Restless legs PMS Menopause Parkinson PTSD Migraine Neuroendokrine Störungen-Tabelle.Bild-2005

39 Chronic Fatigue Syndrome, Fibromyalgia, and Multiple Chemical Sensitivities in a Community-Based Sample of Persons With Chronic Fatigue Syndrome-Like Symptoms 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 % 5,6 % O % 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. Psychosomatic Medicine 62: (2000) Fibromyalgie.Bildserie.2005

40 Occurence of complications in (%) by CFS or in combination CFS with FMS and MCS (Ciccione, 2003)

41 A link between irritable bowel syndrome and fibromyalgia may be related to findings on lactulose breath testing Annals of the Rheumatic Diseases 2004;63: 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. Comparison of the prevalence of abnormal LBT in controls and subjects with IBS and fibromyalgia Fibromyalgie.Bildserie.2005

42 Stressor - Exposition CRH Inflammation Modulation caused by :
environmental factors / harmful substances, over-training, infections EBV/HHV6-Reactivation earlier traumatic events neuroplasticity, genetic factors, allergy, inflammation hypothalamic activation CRH fatigue, depression pain, cognition appetite, craving sleep, motivation aggression, fear chemical intolerance efferent Hyposensitivity blocked Neuroregulation Cortisol Serotonin ACTH, Substance P HGHC Dopamine Noradrenaline GABA Glutamate Inflammation Cytokine activation Virus reactivation, Infection T-cell activation, INK-cell defect Stress.CFS.Stressorexposition.Schema

43 Worldwide Stress CONSUMERS CONCERN ABOUT STRESS & ANXIETY
GREAT 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 worldwide Source: International Labour Office -> European Union : € 20 billion - 40 million workers affected -> United Kingdom : 40 million workdays lost annually -> United States : $ 60 billion million workdays lost annually Source: Guidance on work-related stress/European Commission/Spice of live or kiss of death Stress-related disorders affect nearly 400 million people worldwide Source: WHO-2000 Stress in Deutschland.International-2004

44 Aircraft Noise Raises Blood Pressure Even While People Are Sleeping, Says Study
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 ScienceDaily. Retrieved February 19, 2008,

45 Cardiovascular Events during World Cup Soccer
Daily Cardiovascular Events in the Study Population from May 1 to July 31 in 2003, 2005, and 2006. The FIFA World Cup 2006 in Germany started on June 9, 2006, and ended on July 9, 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 Wilbert-Lampen U et al. N Engl J Med 2008;358: Stress.FußballWM.KHK.Herzinfarkte-NEJM.01.08

46 Catecholamine – Serotonin – ANS-axis
NEURO-REGULATION I Stress hormone axis HPT – AP – ADR Catecholamine – Serotonin – ANS-axis

47 Major components of the central and peripheral stress system
Cholinergic* 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. Paraventricular nucleus Locus ceruleus CRH AVP Pituitary Arcuate nucleaus Noradrenergic system Noradrenaline Cortisol POMC Peptides ACTH Adrenaline Noradrenaline Sympathetic ganglion Noradrenaline Neuropeptides Dorsal root ganglion Stress Resonse System-Scheme.ppt GP Chrousos J Allergy Clin Immunol 2000, 106:S275-91

48 SALIVA CORTISOL IN RELATION TO HIGH AND LOW STRESS
15 Normal Low Stress High Stress Burn-Out Inverted pattern 10 Salivary Cortisol (ng/ml) 5 Morning Lunch Bedtime Stress.Burnout-Cortisol.Saliva-Kurven Stress Saliva Cortisol.ppt P Björntorp , R Rosmond: Obesity and Cortisol : Nutrition 16: , 2000

49 Hypercortisolism ! Result: Diagnosis Endogenous depression 803-0730
Female 60 J., Diagnosis Endogenous depression Refractory to therapy– numerous antidepressants without success – significant weight gain, fear, hot flashes, fatigue, elevated blood pressure Hypercortisolism ! B07 NeuroStress.endDepression.Hypercortisolismus.Therapierefraktär

50 Total Burn-Out ! Result: Diagnostic Diagnosis NeuroStress Profile
, Female 47 J. Diagnostic NeuroStress Profile ADR-Steroid extremely low (ACTH low); NT normal Diagnosis BurnOut Hyperthyroidism, maybe anterior pituitary deficiency Total Burn-Out ! pptB08 Burnut.NNR-Schwäche.Frgl. HVL-Insuffizienz

51 ACTH, plasma cortisol and salivary cortisol responses in CFS patients over time
CortisolPlasma CortisolSaliva Saliva Cortisol ACTH, plasma cortisol and salivary cortisol responses over time and integrated endocrine responses (inserted bar graphs) of CFS patients ( or black) and healthy controls (• or gray) in the TSST CFS.Stresshormonachse.Inflammation-2005 J Gaab et al: Psychoneuroendocrinology (2005) 30:

52 24h urinary cortisol in CFS with and without mental alteration (depression)
120 100 80 60 40 20 CFS with psych. comorbidity Controls Cortisol (nmol / 24h urine) CFS.Cortisol.24hUrin-01.07

53 Stress Acute Stress Chronic Stress Depression Burn-Out
Rapid activation of the HPT-AP-ADR-axis, Cortisol-Noradrenaline/Serotonin increase Acute Stress Chronic hyperactivity of the HPT-AP-ADR-axis, elevated Sympathic tone, genetic disposition Chronic Stress NeuroStress CRH-period stimulation CRH-insensitivity Depression Hypercortisolism Burn-Out Hypocortisolism Fatigue Hypocortisolism 5HT-Deficit Stress.akut.chron.Schema-04.06

54 Catecholamine – Serotonin
NEURO-REGULATION II HPT – AP – ADR Stress hormone axis CNS-ANS-axis Catecholamine – Serotonin GABA - Glutamate

55 Neurotransmitter Neurotransmitters are the chemicals within the vesicles that synaptically separated neurons utilize for chemical communication

56 The impact of neurotransmitters
Noradrenaline Serotonin Dopamine anxiety crankiness cognitive function disposition appetite sex aggression motivation happiness power Ergotropic sympathetic guided potency Trophotropic drive GABA GLUTAMAT Neurotransmitter-Wirkprofile x 2 –04.06

57 Chronic Multisystem Illnesses
CMI Chronic Multisystem Illnesses FMS Fibromyalgia Serotonin is reduced in about 45 % of FMS-patients Increased dopamine sensitivity Substance P, neuro-peptides high CFS Chronic Fatigue Syndrome Serotonin is low in > 80 % of CFS-patients Hypocortisolism DHEA/S low MCS Multiple Chemical Sensitivity Serotonin is low in > 70 % of MCS-patients Latent hypocortisolism Substance P elevation/neuroinflammation ?

58 Possible causes of neurotransmitter troubles
stress unbalanced diet ambient toxins genetic factors illness (Inflammation)

59 Some tryptophan-rich foods as example for 100 Gram:
Lactalbumin 6900 mg Whey protein 2100 mg Egg 1800 mg Nuts mg Pears 1400 mg Potatoes Cheese Onions bananas, curd, cheese, salmon, turkey, duck, avocado, potatoes Tryptophan Serotonin.Tryptophan.Lebensmittel.Bildserie.04.08

60 Tryptophan Metabolism
5% Serotonin Tryptophan Tryptophan Stress/Cortisol Prolactin IFN (IL-12), TNF/PGE2, 95% Immune cell Nerve cell Endothelial cell Liver, kidneys astrocytes TDO IDO SSRI‘s Antioxidants Coxib (iCOX2) Melatonin Bupropion (Zyban, Wellbutrin) SSRI‘s Antioxidants Coxib (iCOX2) Boswellia Kynurenine Quinolinic acid Kynurenic acid Picolinic acid iNOS, NMDA/Glutamate-Agonists iNOS, NMDA/AchR-Antagonist Neurotoxicity Neuroprotection

61 Genetic! Tph 2 5HTTP MAO 5HTA1,2 Tryptophan Serotonin 5-HTP
Hydroxylase Tetrahydrobiopterin Folic acid 5-HTP 5-Hydroxytryptophan Genetic! DOPA -Decarboxylase Vit B6 Serotonin 5HTTP 5HT-Transporter MAO Monoaminoxidase 5HTA1,2 5HT-Receptor

62 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. Accuracy Gene SNP 76,3 % Tph2, NR3C11, NRC1, NR3C12 CRH2 rs , rs , rs6169, rs6188, rs 75,2 % Tph2, NRC1, NR3C12, CRH2 rs , rs6169, rs6188, rs Tph2, COMT, NRC1, NR3C12 CRH2 rs , rs4633, rs6169, rs6188, rs Tph2, Tph22, NR3C11, NRC1 CRH2 rs , rs , rs6169, rs6188, rs CFS. Candidate genes-neurohormoal axis.2006 BN Goertzel et al. Pharmacogenomics (2006) 7:

63 Inflammation ! Tryptophan Kynurenine Serotonin 5-HTP Melatonin
Nicotinic acid Vit B3 NAD/NADH Protein synthesis 5-90% -Interferon Up to 95% IDO Indolamine-2,3-Dioxigenase Tryptophan Kynurenine *very low levels of B-6 required so when B-6 is low this step goes first resulting in increased amounts of xanthurenic acid Tryptophan- Hydroxylase Folic acid 1-10% Vit B6 Serotonin 5-HAT/5-Hydroxytryptamine 5-HTP 5-Hydroxytryptophan > 90% 5-HIES 5-Hydroxyindol- acetic acid N-Acetylserotonin Melatonin Serotonin - Biosynthese.ppt

64 STRESS   INFLAMMATION

65 Cytokine characteristics in CMI
CMI = Chronic Multisystem Illness MCS CFS FM TNF-α (-) IL (-) IL IL IL (+) IFN-gamma /+ IL (+) Patarca R: Cytokines and Chronic Fatigue Syndrome. Ann N.Y Acad Sci 2002: Wallace DJ et al: Cytokines play an aetiopathogenetic role in fibromyalgia: a hypothesis and pilot study. Rheumatology 40: , 2001 Mayer WR, Bartram F, Bieger WP: MCS- Eine chronische Entzündung? Z Umweltmedizin 10: 88 – 96, 2002 Zytokincharakteristika bei CMI

66 Abnormal stress Normal reaction stress reaction
Abnormal stress Normal reaction stress reaction anorexia increased appetite nausea agitation fatigue/exhaustion emotion insomnia added sleep pain analgesia headache, migraine no pain subfebrile temperature no fever metabolic activation metabolic activation (catecholamine, CRF), normalising (glucocorticoid inhibition)   inflammatory reaction relaxed acute phase reaction IL-1, IFN-gamma, TNF-alpha, PGE2 Sickness-Stressreaktion.ppt

67 Inflammation NFkB AP-1 NFAT iNOS Cytokines COX1 5-LOX COX2 ONOO•
Oxidants, harmful substances Cytokines IL1, IL6, TNFa Viruses and germs Acute Stress Noradrenaline UV-light rays Chronic Stress Adrenaline IkBa ROS ROS NFkB AP-1 NFAT ONOO• iNOS Cytokines IL1b, IL8, TNFa, IL6 Gene-activating Phospholipase A2 Arachidonic Acid COX1 5-LOX COX2 Inflammation

68 Nitric Oxide Synthesis
Arginine succinate NOS Arginine + O NO + Citrulline  NO2 + NO3 eNOS nNOS mtNOS iNOS

69 Mitochondria are the fountain of energy for the body
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. Mirochondrien.Enerhgiestoffwechsel.2005

70 Result 2-2 Diagnosis: Treatment: Whiplash injury Female, 57 J. VS
Fatigue EBV-reactivation, Anxiety disorder Treatment: Fresh cell extracts (adrenal), Micronutrients including: OPC, carnitine, alpha-lipoic acid, curcumin, omega-3 BE Neurostress.KKT.Atlas. BHS.S100.NoTyrosin.2005

71 Treatments: Fresh cell extract (adrenal/thymus) Micronutrients including: OPC, carnitine, alpha-lipoic acid, curcumin, omega-3 Page 2 S ,6 NSE BE Neurostress.KKT.Atlas. BHS.S100.NoTyrosin.2005

72 FATIGUE – DIAGNOSTIC I. NeuroStress
Cortisol 8, 12, 20 hrs; DHEAS 8, 20 hrs Catecholamine (Adrenaline, Noradrenaline, Dopamine), Serotonin,GABA, Glutamat e Glycine, Taurine, Glutamine, TSH, ACTH, Prolactin II. 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

73 CFS – diagnostic ladder
Grade I Cortisol 8, 12, 20 hrs; DHEAS 8, 20 hrs Catecholamine (Adrenaline, Noradrenaline, Dopamine) Serotonin,GABA, Glutamate Grade II ITT©, EBV (RNA/DNA), Borrelia-Ab NF-kB, Cytokine: CRPs, TNF,IFN GSH, Hocy, Vit B6, Q10, Vit D, TSH, Ferritin Grade III HHV6 (DNA), CMV-Ab,NK-Check ANA, IgG, IgA, IgM, IgE Grade IV Nitrotyrosine, S-100, Zn (E), Se (E), Mg (E) ACTH, Prolactin, Testosterone Immune status CMI.CFS.FMS-Diagnsotik.Therapie.Schema-06.08

74 Pivotal neurotransmitter concept
Rearrangement of the balance between Excitation (Adrenaline, Noradrenaline, Glutamate, Histamine) Inhibition (GABA, Serotonin, Glycine, Theanine) AS-Therapie.Inhib.Excit-Konzept-04.06

75 Amino acids/Neurotransmitters
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

76 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: mg / day NeuroStress.AS-Therapie.Wirkstoffe x

77 GABA (Gamma Aminobutyric acid)
Glutamine GABA-synthesis 5-HT(P) stimulation of GABA-activity 5-HT is necessary for GABA function Theanine increase GABA effect promote GABA synthesis Melatonin increase GABA-binding Taurine GABA-receptor modulation ++ Neuroprotective, blocks Glutamate toxicity Benzodiazepine Locked on GABA-Receptor, high affinity Rhodiola Excitatory in low doses, inhibitory in high doses Barbiturate promoteGABA-effect Progesterone increase GABA-effect ++ Neuroprotective (allo-Pregnanolone) GABA-Rezeptor.Regulation.Schemata-2007

78 FATIGUE -THERAPY Level I Indiv. micronutrients Or
5-HTP mg Taurine mg Theanine mg NAC mg plus: Vit B6, B12, Vit C, Folic acid, Mg, Zn, Se Or Indiv. micronutrients 5-HTP mg Tyrosine mg Glutamine mg Taurine mg Theanine mg plus: Vit B6, Vit C, Folic acid, Tocopherol, Mg Level II Indiv. micronutrients 5-HTP mg Tyrosine mg NAC mg Theanine mg plus: Vit B6, Vit C, Folic acid, Calcium CMI.CFS.FMS-Diagnsotik.Therapie.Schema-06.08

79 Melatonin Neuroprotection
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

80

81 Patient: C.J. (04/13/44) m. Diagnosis: Therapy: Fresh cell extracts
CFS following drug abuse over 20 years, Osteopenia, Lack of concentration Therapy: Fresh cell extracts ( thymus, cerebrum, gut ) Detox

82 Patient: C,J (04/13/44) m.

83 Patient: M.J. (12/11/62) f. Diagnosis: Therapy: Fresh cell extracts
Coma for 4 months following accident Meningitis, Adrenal dysfunction Therapy: Fresh cell extracts (brain, adrenal, gut, cartilage) Hormone balance

84 Patient: M,J ( )

85 Patient: M,J ( )

86 Patient: H.G. (01/08/64) m. Diagnosis: Therapy: Fresh cell extracts
Hemochromatosis Heavy metal intoxication Diabetes - Type II Therapy: Fresh cell extracts (adrenal, pancreas, liver, thymus) Detox

87 Patient: H.G. (08/01/64) m.

88 Patient: H.G. (08/01/64) m.

89 Patient: H.G. (08/01/64) m.

90 Patient: H.G. (08/01/64) m.

91 Patient: F-K.G. (09/03/39) f. Diagnosis: Therapy: Fresh cell extracts
Multiple Sclerosis, Irritable bowel syndrome CFS Therapy: Fresh cell extracts (nerve, brain, gut, adrenal, thymus) Physiotherapy

92 Patient: F-K.G (09/03/39) f.

93 Patient: F-K.G (09/03/39) f.

94 Patient: F-K.G (09/03/39) f.

95 Patient: F-K.G (09/03/39) f.

96 Patient: F-K.G (09/03/39) f.

97 Patient: G.U. (08/19/54) f. Diagnosis: Therapy: Fresh cell extracts
Heavy metal intoxication CFS Hormonal imbalance Therapy: Fresh cell extracts (ovary, adrenal, thymus) Detox

98 Patient: G.U. (08/19/54) f.

99 Patient: G.U. (08/19/54) f.

100 Patient: G.U. (08/19/54) f.

101 I hope you didn’t fall asleep…
Thank you very much for your kind attention!

102 privat clinic Dr. Ursula Jacob Silberwaldstraße 34
Samstag, 8. April 2017 privat clinic Dr. Ursula Jacob Silberwaldstraße 34 72280 Dornstetten-Hallwangen Tel.: +49 (0) 7443 – – 0 Fax: +49 (0) 7443 – – 99 Samstag, 8. April 2017


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