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Apocalypse23.
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Per gli utenti che desiderano segnalare documenti da tradurre.
potete farlo qui.
Chi poi tradurrà è pregato di confermare, la traduzione in corso, sempre qui.
Ricordiamo che è sempre prferibile fare delle sintesi ( Abstract).
Edited by Apocalypse23 - 4/8/2009, 12:14. -
uonderuoman.
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http://www.investinme.org/Documents/Hooper...lt%20Slides.pdf
Engaging with M.E.
Prof. Malcolm Hooper
Emeritus Professor of Medicinal Chemistry
University of Sunderland
Sparshalt College
14 November 2005
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uonderuoman.
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How Enzyme Therapy works File Allegato
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uonderuoman.
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http://www.i-sis.org.uk/ispr-summary.php?printing=yes
non puo essere riprodotto senz
autorizz----
Dozens of prominent scientists from seven countries, spanning the disciplines of agroecology, agronomy, biomathematics, botany, chemical medicine, ecology, histopathology, microbial ecology, molecular genetics, nutritional biochemistry, physiology, toxicology and virology, joined forces to launch themselves as an Independent Science Panel on GM at a public conference, attended by UK environment minister Michael Meacher and 200 other participants, in London on 10 May 2003.
The conference coincided with the publication of a draft report, The Case for a GM-free Sustainable World, calling for a ban on GM crops to make way for all forms of sustainable agriculture. This authoritative report, billed as "the strongest, most complete dossier of evidence" ever compiled on the problems and hazards of GM crops as well as the manifold benefits of sustainable agriculture, is being finalised for release 15 June 2003.
Ahead of the release of the 120-page final report, the Independent Science Panel is pleased to provide a four-page summary as its contribution to the National GM Debate in the UK.
It is a challenge to the proponents of GM to answer the case presented, rather than having to argue against the case for GM crops, which has yet to be made.
Please circulate this document widely.
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uonderuoman.
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aiuta a spiegare perché un virus comune, che ha poco effetto sulla maggior parte delle persone può avere un tale impatto su altri
retrovirus Herv-K18
http://www.marketwire.com/press-release/Hh...ion-871774.html
Jun 23, 2008 10:00 ET
Ancient Retrovirus May Contribute to Chronic Fatigue Syndrome, Multiple Sclerosis and Autoimmunity
Smoldering Infections of Two Common Viruses EBV and HHV-6 Cause Inherited Retrovirus Genes to Activate
BALTIMORE, MD--(Marketwire - June 23, 2008) - Brigitte Huber, PhD, of the Tufts University School of Medicine, presented evidence at a medical conference that suggested that a reactivated ancient retrovirus embedded in the human genome may be active in chronic fatigue syndrome (CFS) and multiple sclerosis (MS) patients. Danish scientists at the same conference suggested that the activation of this retrovirus, dormant in healthy individuals, could be the reason why autoimmune conditions worsen with viral infections.
Chronic Fatigue Syndrome and Multiple Sclerosis Patients at Increased Risk From the Effects of HERV-K18 Activation
"Patients with profoundly fatiguing diseases such as MS and CFS may be particularly susceptible to HERV-K18 activation," said Dr. Huber. The announcement was made at the International Symposium on Viruses in CFS and Post-Viral Fatigue, a satellite conference of the 6th International Conference on HHV-6 & 7. Using an SNP-based genotyping method, Dr. Huber found that both MS and CFS patients (whose illness had been triggered by infectious mononucleosis) were at a higher relative risk for containing HERV-K18 variants known to induce superantigen activity. Superantigens are proteins that are able to induce a strong undifferentiated T-cell response believed to deplete the immune system over time.
Viral activity and/or immune activation has been shown to trigger HERV-K18 activity. Both Epstein-Barr virus infection (infectious mononucleosis) and interferon-alpha administration are associated with HERV-K18 activity. "HHV-6 activates HERV-K18 as well," said Danish investigator Per Hollsberg, MD and professor from the University of Aarhus In Denmark. His PhD student Vanda Lauridsen Turcanova presented this data at the same conference. "Furthermore, this retrovirus activation may have important consequences for autoimmunity," he added.
HERV-K18 activation may be the endpoint of an HHV6/EBV interferon pathway operating in both MS and CFS. HHV-6 is being investigated as a co-factor in both diseases. Other retroviruses, HERV-H and HERV-W, have been implicated in MS by other researchers. Over 75% of MS patients meet the criteria for CFS. Fatigue is often the most disabling symptom for MS patients. The two diseases also share characteristics such as grey matter atrophy, impaired cerebral glucose metabolism, autonomic nervous system activity and altered patterns of brain activity.
Dr. Huber's study suggests that endogenous retroviral activation in CFS and MS could produce some of the symptoms associated with both diseases. She has received a National Institutes of Health (NIH) grant to study these issues. Per Hollsberg has done extensive research on the role of EBV and HHV-6 in multiple sclerosis.
The HHV-6 Foundation
The HHV-6 Foundation encourages scientific exchanges and provides grants to researchers seeking to increase our understanding of HHV-6 infection in a wide array of central nervous system disorders. Daram Ablashi, the co-discoverer of the HHV-6 virus, is the Foundation's Scientific Director.
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uonderuoman.
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Magnesium Taurate is a scientifically-designed amino acid-mineral
complex. Magnesium Taurate is a fully reacted complex and not simply
a blend of the two materials. Unlike some other magnesium
preparations, magnesium taurate does not cause gastrointestinal
upset. Magnesium Taurate is routinely used to help support healthy
heart rhythm. Studies have revealed magnesium & the amino acid
taurine have some interchangeable & potentiating roles. Magnesium
helps to regulate taurine & taurine can substitute for magnesium when
magnesium is deficient. Both taurine & magnesium stabilize cell
membranes. Both exert sedative effects & inhibit the excitability of
nerve cells throughout the central nervous system..
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Like the neurotransmitter, GABA, taurine has a calming effect on the brain, inhibiting the excitation of nerve cells. GABA deficiencies are commonly found in children diagnosed with autism, migraines and/or ADD. Taurine has been shown inhibit the firing of nerve cells and rectifies abnormal concentrations of glutamate. Magnesium also blocks the excito-toxic effects of glutamate. Magnesium plays an important role in the metabolic regulation of taurine and taurine can substitute for magnesium in the presence of magnesium deficiencies.
Both glutamate (found in monosodium glutamate - MSG) and aspartate (found in diet-pop sweetened with aspartame) are excito-toxins that can over-stimulate the firing of nerve cells in children whose brains do not produce enough of the calming neurotransmitter, GABA. It is theorized by some autism researchers that the presence of mercury in the brain can inhibit the production of GABA. When not enough GABA is present, these excito-toxins over-stimulate the nerves, resulting in stunting and/or killing off of nerve cells.
A typical physical reaction to excito-toxins could be a child becoming extremely hyperactive upon ingesting the excito-toxin for several hours, followed by one or more days of lethargy an/or regression. Using the magnesium-taurine complex may help normalize this hyperexcitiability, protecting the brain's nerve cells.
Needless to say, children within the autism spectrum should avoid products that contain excito-toxins, such as (MSG (labelled on foods as MSG, monosodium Glutamate, Modified Food Starch, and can be hidden within the catch-all ingredient, "Natural Flavorings"). Also any foods containing aspartame, such as diet pop should avoided.
A related supplement that is effective in protecting the GABA producing area of the brain and promotes the production of GABA is Carn-Aware.. -
uonderuoman.
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New Test For Mysterious Metabolic Diseases
ScienceDaily (Feb. 16, 2009) — Scientists at Stanford University School of Medicine have devised a much-needed way to monitor and find treatments for a mysterious and devastating group of metabolic diseases that arise from mutations in cells' fuel-burning mechanism.
Mitochondrial disorders can cause organ failure, seizures, stroke-like episodes and premature death. The diseases—more than three dozen in total—arise from genetic errors of the mitochondria, the cell structures that process oxygen and turn food molecules into useable energy. Mitochondrial disorders affect one in 4,000 kids and one in 8,500 adults. They are difficult to diagnose, and no treatments or cures exist.
But that could soon change. A team at Stanford and Lucile Packard Children's Hospital has discovered a biological marker they can use to monitor the diseases. The finding will enable researchers to hunt for treatments and help physicians check patients' status before health crises erupt. The research was published online Feb. 9 in the Proceedings of the National Academy of Sciences.
"When a car engine doesn't work right, it smokes," said senior study author Greg Enns, MB, ChB, who is professor of pediatrics at Stanford University School of Medicine and director of the biochemical genetics program at Packard. "What we looked for is, in essence, biochemical smoke."
Like a car engine, when mitochondria are not burning fuel cleanly, they kick out nasty gunk. Defective mitochondria produce large quantities of oxygen free radicals—highly reactive molecules that damage DNA and cell structures. Comparing patients who have a mitochondrial disorder with healthy people in the control group, Enns' team searched for signs that free radicals overtax patients' natural antioxidant defense systems. And they found it.
"Even when these patients are coming into the clinic looking pretty healthy, they have evidence of extra metabolic stress," Enns said, noting the findings were surprising because none of the patients were in the midst of a health crisis such as organ failure when blood samples were taken. It is the first time such signs have been uniformly shown in the blood of patients across a wide range of mitochondrial disorders, he added.
The team saw that levels of glutathione, the body's primary antioxidant, were significantly reduced in white blood cells from the 20 mitochondrial disease patients in the study. The observation means patients' antioxidant defenses were indeed depleted. Glutathione was also diminished in nine patients with organic acidemias, another group of metabolic diseases that researchers think may be associated with aberrant mitochondrial function.
A second finding gave the researchers a big hint about where to hunt for treatments. Patients taking antioxidant supplements did not have depleted glutathione, they found. Scientists have long suspected antioxidants such as vitamin C and vitamin E might help patients with mitochondrial disease or organic acidemias, and doctors sometimes suggest the supplements to their patients. But no one has been able to test whether they work.
"As a clinician, one of the most frustrating things has been not being sure if supplements are doing any good," said Enns. "Now we're able to take a baseline blood reading and see 'before' and 'after' snapshots."
William Craigen, MD, PhD, the director of the metabolic clinic at Texas Children's Hospital, called this finding "the beginning of insight into the mechanisms of mitochondrial disease." Craigen, who is also medical director for the mitochondrial diagnostic lab at Baylor College of Medicine, was not involved in the Stanford study. "This new research provides an opportunity to start treating a heterogeneous group of diseases in a single fashion, with a simple and easy-to-administer treatment, potentially improving patients' long-term outcomes," he added.
Glutathione measurements could also help diagnose patients, Enns said, by giving physicians a clear indication that something is awry in the mitochondria. Genetic and molecular tests have already led to increases in the number of diagnoses, but the diagnosis is still difficult to pin down.
The method Enns' team used to measure glutathione, called high-dimensional flow cytometry, has limitations: it requires very fresh blood samples, uses expensive equipment only available in research labs, and provides relative rather than absolute glutathione measurements. Now that the team knows what metabolic change to look for, they're working to develop a more broadly applicable measurement technique.
And glutathione measurements could help scientists unravel other disease mysteries, too. "You name the disease, you can postulate mitochondrial involvement," Enns said. "It's been proposed for everything from poor vision to hearing loss, kidney disease, liver disease, autism spectrum disorders, diabetes, Alzheimer disease, cancers. Our work could lead to research on therapies for a broad range of disorders."
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uonderuoman.
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MARTIN PALL -TEORIA NO-ONOO
http://www.ei-resource.org/articles/chroni...-for-treatment/
Thirty agents or classes of agents predicted to down-regulate NO/ONOO cycle biochemistry:
Agent or Class of Agents Clinical Trial Data or Clinical Observation/Anecdotal Reports
Vitamin C (ascorbic acid) - Clinical Trial Data
Tocopherols/Tocotrienols - Anecdotal Reports
Selenium - None
Carotenoids - None
Flavonoids - Clinical Trial Data
Reductive stress relieving agents - Clinical Trial Data
Mitochondrial regeneration agents - Clinical Trial Data
L-Carnitine/Acetyl-L-carnitine - Clinical Trial Data
Hydroxocobalamin/B12 - Clinical Trial Data
Folic acid - Clinical Trial Data
Vitamin B6/pyridoxal phosphate - Anecdotal Reports
Riboflavin - None
Other B vitamins - None
Glutathione/glutathione precursors - Clinical Observations
alpha-Lipoic acid - None
Magnesium - Clinical Trial Data
SOD minerals/zinc,manganese, copper - None
NMDA antagonists - Clinical Trial Data
Riluzole - None
Taurine - None
Inosine/uric acid - None
Long chain omega-3 fatty acids - Clinical Trial Data
Agents that lower NF-kappa B activity - Anecdotal Reports
Curcumin - None
Algal supplements - Clinical Trial Data
Hyperbaric oxygen - Clinical Trial Data
Minocycline and Other Tetracyclines - Clinical Observations
Creatine - None
Lowered vanilloid activity - None
Carnosine - None
TRH - Clinical Observations
You will note that there is clinical trial data on the efficacy of 12 of these agents or classes of agents, and there are clinical observations and/or anecdotal evidence of efficacy of six others. Nonetheless, each of these individually, have limited efficacy, suggesting that combinations may be more effective than are individual agents.
SEGUE: Treatment protocols of five different physicians
Agents from Cheney Protocol Predicted to Down-Regulate NO/ONOO- Cycle Biochemistry
High dose hydroxocobalamin (B12) injections - nitric oxide scavenger
Whey protein - glutathione precursor
Guaifenesin - vanilloid antagonist?
NMDA blockers
Magnesium - lowers NMDA activity
Taurine - antioxidant and acts to lower excitotoxicity including NMDA activity
GABA agonists - GABA acts as an inhibitory neurotransmitter to lower NMDA activity - these include the drug neurotin (gabapentin)
Histamine blockers - mast cells which release histamine are activated by both nitric oxide and vanilloid stimulation and may therefore be part of the cycle mechanism
Betaine hydrochloride (HCl) - Betaine lowers reductive stress, the hydrochloride form should only be used in those with low stomach acid. Betaine (trimethylglycine) is also listed separately in the protocol description
Flavonoids, including "bioflavonoids," olive leaf extract, organic botanicals, hawthorn extract
Vitamin E (forms not listed)
Coenzyme Q10 - acts both as antioxidant and to stimulate mitochondrial function
A-lipoic acid
Selenium
Omega-3 and -6 fatty acids
Melatonin - as an antioxidant
Pyridoxal phosphate - improves glutamate/GABA ratio
Folic acid - lowers uncoupling of nitric oxide synthases
Agents from Teitelbaum Protocol Predicted to Down-Regulate NO/ONOO Cycle Biochemistry
Daily energy B-complex - B vitamins including high dose B6, riboflavin, thiamine, niacin and also folic acid. These fall into four categories that I have listed earlier in the chapter
Betaine hydrochloride (HCl) - lowers reductive stress, hydrochloride -form should only be taken by those deficient in stomach acid
Magnesium as magnesium glycinate and magnesium malate - lowers NMDA activity - often uses magnesium injections
A-Lipoic acid - important antioxidant helps regenerate reduced glutathione
Vitamin B12 IM injections, 3 mg injections (does not state whether this is hydroxocobalamin) - may act as potent nitric oxide scavenger
Eskimo fish oil - excellent source of long chain omega-3 fatty acids. Lowers iNOS induction, anti-inflammatory
Vitamin C
Grape seed extract (flavonoid)
Vitamin E, natural - does not state whether this includes g-tocopherol or tocotrienols
Physician's protein formula, used as glutathione precursor
Zinc - antioxidant properties and copper/zinc superoxide dysmutase precursor
Acetyl-L-carnitine - important for restoring mitochondrial function
Coenzyme Q10 - both important antioxidant properties and stimulates mitochondrial function
Agents from Nicolson Protocol Predicted to Down-Regulate NO/ONOO- Cycle Biochemistry
Other phosphatidyl polyunsaturated lipids - this and the phosphatidyl choline are predicted to help restore the oxidatively damaged mitochondrial inner membrane
Magnesium - lowers NMDA activity, may aid in energy metabolism
Taurine - antioxidant activity and lowers excitoxicity including NMDA activity
Artichoke extract - as flavonoid source?
Spirulina - blue-green alga is a concentrated antioxidant source
Natural vitamin E - does not tell us whether this includes g-tocopherol or tocotrienols
Calcium ascorbate - vitamin C
a-Lipoic acid - important antioxidant, key role in regeneration of reduced glutathione, but also has role in energy metabolism
Vitamin B6 - balance glutamate and GABA levels, lowers excitotoxicity
Niacin - role in energy metabolism
Riboflavin - important in reduction of oxidized glutathione back to reduced glutathione; also has important role in mitochondrial function
Thiamin - role in energy metabolism
Vitamin B12 - as nitric oxide scavenger?
Folic acid - lowers nitric oxide synthase uncoupling
Agents from Petrovic Protocol Predicted to Down-Regulate NO/ONOO- Cycle Biochemistry
Valine and isoleucine - branched chain amino acids known to be involved in energy metabolism in mitochondria, and may be expected,therefore, to stimulate energy metabolism; modest levels may also lower excitotoxicity
Pyridoxine (B6) - improves balance between glutamate and GABA, lowers excitotoxicity
Vitamin B12 in the form of cyanocobalamin - cyanocobalamin is converted to hydroxocobalamin in the human body but the latter form will be more active as a nitric oxide scavenger, since it does not require such conversion
Riboflavin - helps reduce oxidized glutathione back to reduced glutathione
Carotenoids (alpha-carotene, bixin, zeaxanthin and lutein) - lipid (fat) soluble peroxynitrite scavengers
Flavonoids (flavones, rutin, hesperetin and others)
Ascorbic acid (vitamin C)
Tocotrienols - forms of vitamin E reported to have special roles in lowering effects of excitotoxicity
Thiamine (aneurin) - B vitamin involved in energy metabolism
Magnesium - lowers NMDA activity; may aid energy metabolism
Zinc - precursor of SOD
Betaine hydrochloride (HCl) - lowers reductive stress, hydrochloride form should only be used by those deficient in stomach acid
Essential fatty acids including long chain omega-3 fatty acids
Phosphatidyl serine - reported to lower iNOS induction
Agents from Pall/Ziem Protocol Predicted to Down-Regulate NO/ONOO- Cycle Biochemistry
Nebulized, inhaled reduced glutathione
Nebulized, inhaled hydroxocobalamin (some use sublingual)
Mixed, natural tocopherols including g-tocopherol
Buffered vitamin C
Magnesium as malate
Four different flavonoid sources: Ginkgo biloba extract, cranberry extract, silymarin, and bilberry extract
Selenium as selenium - grown yeast
Coenzyme Q10
Folic acid
Carotenoids including lycopene, lutein and b-carotene
a-Lipoic acid
Zinc (modest dose), manganese (low dose) and copper (low dose)
Vitamin B6 in the form of pyridoxal phosphate
Riboflavin 5'-phosphate (FMN)
Betaine (trimethylglycine)
Dr. Ziem has recently added two additional agents: green tea extract (flanonoids) and acetyl L-carnitine.
Let me add three additional important points:
It is important, with all of these treatments, to avoid up-regulating NO/ONOO- cycle biochemistry. A number of things will tend to produce such up-regulation. These include chemical exposure in MCS patients, excessive exercise in CFS patients, excitotoxin exposure (including MSG and aspartame) in all of these diseases/illnesses, exposure to food allergens in those who have food intolerances and psychological stress in those sensitive to such stress. These treatments are only effective when the agents down-regulating NO/ONOO- cycle biochemistry are taken along with avoidance of stressors predicted to up-regulate such biochemistry.
The second point is that I think that all of these protocols can be improved and I suspect that the physicians who developed them would agree with this. Nevertheless, I would argue that we now know how to effectively treat these diseases/illnesses and that such treatment consistently involves down-regulating the fundamental etiologic cycle that causes them.
The third is that we now have sufficient evidence supporting the NO/ONOO cycle etiology of these diseases/illnesses. This is the only detailed explanation for the many overlaps among these illnesses, their substantial comorbidity with each other and the extraordinary variation in symptoms and signs from one case to another. In other words these are true diseases, with a defined morbid process and etiology, albeit ones with unusual variation from case to case due to the local nature of the underlying biochemistry. This is a major new paradigm of human disease, and there are other diseases/illnesses that are candidates for inclusion under this paradigm."
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Apocalypse23.
User deleted
Brava ciccina la metto in coda.......molto interessante, la aggiungerò
agli altri protocolli.
Ciao Ispettore Gadget.
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uonderuoman.
User deleted
Hypothesis ME CFS hydrogen sulfide metabolismJournal: Med Hypotheses. 2008 Sep 15. [Epub ahead of print]
Author: Marian Dix Lemle, Washington, DC 20008, United States, Fax: +1 202 775 0045
NLM Citation: PMID: 18799269
http://www.prohealth.com/fibromyalgia/blog....cfm?id=1314423
Here the hypothesis is advanced that the multi-system disturbances in CFS/ME are caused by disturbances in the homeostasis of endogenous hydrogen sulfide (H2S) and result in mitochondrial dysfunction.
Research on H2S -- the gas that causes the characteristic smell of rotten eggs -- dates to the 1700 s and has shown a remarkable range of effects in both animals and humans. At high concentrations, H2S has a variety of biological toxicities including being instantaneously deadly; at low concentrations some evidence suggests that H2S has beneficial effects and can act as an endogenous biological mediator the third such gaseous mediator discovered (after nitric oxide and carbon monoxide).
The brain, pancreas and the gastrointestinal tract produce H2S. Endogenous H2S plays a role in regulating blood pressure, body temperature, vascular smooth muscle, cardiac function, cerebral ischemia, and in modulating the hypothalamus/pituitary/adrenal axis. It even has been called a "master metabolic regulator."
Recent research has demonstrated that at low, non-toxic doses, exogenous H2S produces a reversible state of hibernation-like deanimation in mice, causing a decrease in core body temperature, an apnea-like sleep state, reduced heart and respiration rates, and a severe metabolic drop [1]. These characteristics are not unlike the symptoms and extreme "de-animation" experienced by CFS/ME patients.
Moreover, H2S affects biological networks that are disrupted by CFS including neurologic, endocrine and immunologic systems. Therefore, a plausible etiology of CFS is an increase in the activity of endogenous H2S, thereby inhibiting mitochondrial oxygen utilization.
H2S and Mitochondria In this view, fatigue and the other CFS/ME symptoms could be due to diminished physiological and cellular energy due to reduction in the capacity of mitochondria to utilize oxygen and synthesize ATP. Specifically, H2S binds to the mitochondrial enzyme cytochrome c oxidase, which is part of Complex IV of the electron transport chain, and attenuates oxidative phosphorylation and ATP production.
Consistent with this finding, recent research on low level H2S toxicity points to increased formation of free radicals and depolarization of the mitochondrial membrane, a condition that would decrease ATP synthesis [2].
If poisoning renders mitochondria inefficient, one would expect cells to shift to anaerobic mechanisms, a shift that has been reported for CFS patients. Also consistent with this hypothesis is the fact that mitochondria are organelles descended from ancient eukaryotic sulfur-utilizing microbes. Thus, it is not surprising that they show a very high affinity for sulfide.
Of course, H2S or sulfide may not directly affect mitochondria by binding to them. Genomic changes could mediate some of the effects of H2S. Some studies have found evidence for the involvement of the cytochrome c oxidase gene in CFS/ME.
Also, investigators have found CFS abnormalities in genes related to fatty acid metabolism, apoptosis, mitochondrial membrane function, and protein production in mitochondria.
Given a predisposing genetic background, H2S may lead to genomic instability or cumulative mutations in the mitochondrial DNA [3].
Alternatively, the effects of H2S could be initially mediated by changes in the redox potential of cells or changes in their sulfur metabolism, especially in glutathione.
Another possible mechanism is a direct effect of H2S on the immune system. Recent research indicates that exogenous hydrogen sulfide induces functional inhibition and cell death of cytotoxic lymphocyte subsets of CD8 (+) T cells and NK cells.
Finally, H2S plays a pivotal role in both aerobic and non-anaerobic organisms as a signaling molecule.
Bacteria in the gut both produce H2S and utilize it as a substrate alternative to oxygen. This is of particular relevance in the gastrointestinal tract, where unusually high levels of gram-negative bacteria, which increase intestinal permeability, have been found in patients with CFS/ME [4].
In addition to bacteria, yeast, mold and other fungi also emit H2S. CFS/ME is a model disease for multisystem disturbance. It is my hypothesis that mitochondria, organelles required by every cell to sustain life, are unable to adequately utilize oxygen.
This mitochondrial disturbance could be due to the combined effects of anaerobic conditions known to occur in CFS and associated low-level H2S toxicity. This increase in H2S alters fine signaling necessary for body homeostasis, and causes CFS.
Understanding the role of H2S in the body, and, in particular, in mitochondrial function, may provide a unifying lens through which to view the diverse manifestations of this complex disease.
References [1] Blackstone Eric, Morrison Mike, Roth Mark B. H2S induces a suspended animation-like state in mice. Science Magazine 2005;308(5721):518. doi:10.1126/science.110858. [2] Eghbal MA, Pennefather PS, O Brien PJ. H2S cytotoxicity mechanism involves reactive oxygen species formation and mitochondrial depolarisation. Toxicology 2004;203(13):6976. PMID: 15363583. [3] Attene-Ramos MS, Wagner ED, Gaskins HR, Plewa MJ. Hydrogen sulfide induces direct radical-associated DNA damage. Mol Cancer Res 2007 [PMID: 17475672]. [4] Maes M, Mihaylova I, Leunis JC. Increased serum IgA and IgM against LPS of enterobacteria in chronic fatigue syndrome (CFS): indication for the involvement of gram-negative enterobacteria in the etiology of CFS and for the presence of an increased gut-intestinal permeability. J Affect Disord 2007;99(13):23740. PMID: 17007934.. -
uonderuoman.
User deleted
TRATTO DA :
http://www.iacfsme.org/IACFSMEConferenceMo...73/Default.aspx
THE 9th INTERNATIONAL IACFS/ME RESEARCH AND CLINICAL CONFERENCE
Peppermill Resort, Reno, Nevada, USA
12-15th March 2009
Summary by Rosamund Vallings, M.B., B.S.
...a me è parso nulla di nuovo...
a parte Cheney con le staminali..
e che pur essendo del 99 non sapevo di questo
Cryptostrongylus pulmoni Lawrence Klapow
Pharmacologic and non-pharmacologic treatment advances
Effectiveness of oral NADH in the treatment of CFS - Jose Allegre (Barcelona Spain) concluded that oral NADH does not seem to modify clinical variables, but some benefits were seen in anxiety levels, but depression increased. In effort tests there was some significant reduction of maximum FC.
Partner relationship influence on functional capacity in CFS women – A.Blazquez (Barcelona,Spain) – Neurocognitive dysfunction correlated positively with the relationship and significantly influenced ventilation and supramaximal exercise.
Role of erythrocyte aggregation and deformability in CFS – Ekua Brenu (Gold Coast<Australia) – found that there were no abnormal changes in the rheological characteristics of erythrocytes in CFS. Deformability and aggregation are not therefore likely to be markers for CFS.
Post-Cancer Fatigue (PCF) is not associated with altered cytokine production – Barbara Cameron (Sydney,Australia) – findings argue strongly against the notion that PCF is mediated by peripheral inflammation.
Pacing as a dynamic embedded, embodied treatment/prevention strategy in CFS – Bruce Carruthers (Vancouver,Canada) – Pacing is a strategy that patients learn gradually to adjust their activity/rest sequences and treat their fatigue in a preventative way.
Oxygen toxicity as a locus of control for CFS – Paul Cheney (Ashville, USA) – Concluded that CFS is an oxygen toxic state. This is less a cause of CFS but a final common pathway downstream from etiologies, but which may determine outcome.
Cell associated therapy for CFS – Paul Cheney (Ashville,USA) – has found that therapy with low molecular weight peptides from cell-associated mammalian tissue homogenates (porcine) appear to offer significant benefit in CFS. Use of several tissue extracts appears to be more successful than only one.
Oxymatrine for the treatment of CFS associated with chronic enterovirus infection – J.Chia (Lomita,USA) – This treatment showed significant benefit, with a shift in immune response in the Th1 direction, which correlated with symptomatic response. Oxymatrine maybe an effective immune modulator in CFS before definitive antiviral therapy becomes available.
Serving Students with CFS and other chronic illnesses – Patricia Fennell (New York, USA) – described a workshop for educators to discuss the needs of of those with chronic illnesses. As a result educational services can be improved for students using the Fennell Four Phase Model.
US Government strategy and funding of CFS research compared to similar illnesses – Kenneth Friedman (Newark, USA) – Of the US Government research effort into neuro-endocrine-immune disorders (NEIDs), Lyme disease has shown the most progress. Despite the government spending more on GWI there is still no diagnostic test or specific medication. New research strategies and funding mechanisms are needed for illnesses such as CFS.
Amygdala retraining techniques may improve outcomes for patients with CFS – Ashok Gupta (London,UK) – had done a clinical audit of subjective outcomes. This revealed higher rates of improvement in comparison to remission rates in other intervention studies. No control or placebo group was used and future studies will incorporate this.
Treatment of Cryptostrongylus pulmoni, a new parasite found in CFS – Lawrence Klapow (Santa Rosa,USA) – This is a chronic roundworm parasite found in a number of patients studied. It reproduces in the lungs and GI tract. It appears to trigger CFS symptoms during its reproductive stage. Symptoms were relieved with Ivermectin, weekly inhalations with nebulised ethanol and treatment of the GI tract with anthelminthics.
Predictors of fatigue in patients with MS – Anners Lerdal (Drammen,Norway) – The main predictors of fatigue were fatigue scores and fatigue caseness at baseline. Poor general health and perceived cognitive impairment also predicted higher levels of fatigue.
Is there an association between exposure to chemicals and CFS? – Luis Nacul (London,UK) – existing evidence remains inconclusive as to the association between exposure to chemicals and CFS, and there is need for well designed epidemiological studies.
Similarities of CFS and autism spectrum disorders: comparison of blood co-infections – Garth Nicolson (Huntingdon Beach,USA) – Chronic infections are similar in both those with CFS and a large subset of patients with neurobehavioural disease. The 3 infections seen were mycoplasma species, Chlamydia pneumoniae and HHV6.
Effects of a dietary weight supplement on fatigue, appetite suppression and weight-loss: implications in CFS – Garth Nicholson (Huntingdon Beach,USA) – The product used was an amaylase inhibitor plus NT factor (HealthyCurb). Notable appetite suppression occurred coupled with significant weight loss. The group showed an overall decrease in fatigue, with improvement in lipid profiles and cardiovascular health. There were no adverse effects clinically or biochemically. This seems a safe option for those with CFS wanting to lose weight.
Improved renal function in CFS patients with IV immunoglobulin treatment – Tae Park (Seoul,Korea) – Improved renal blood flow as a result of this trial may be evidence of corresponding cerebral blood flow, as patients on treatment experienced improved cognition. A further poster looked at the risk of CFS patients developing chronic kidney disease. The risks showed decreased glomerular filtration rate in many CFS patients, and recommendations are that kidney function should be checked regularly in CFS. Cognitive function was further investigated in another poster with positive outcome in those treated with IV immunoglobulin.
Lymphatic drainage of the neuroaxis and the central rhythm impulse – Ray Perrin (Preston,UK) – hypothesized a model for pathological links to CFS. Cranial rhythm impulse may be the rhythm produced by a combination of cerebrospinal drainage of the neuroaxis and sympathetic induced pulsations of the central lymphatic drainage. Osteopathic manual treatment can reduce the severity of CFS.
Muscle fatigue in CFS and its response to a novel manual therapeutic response – Ray Perrin (Preston,UK) found that post-exercise muscle function in CFS is improved following specialized osteopathic intervention. Fatigue in this disorder is considered not due to myopathic changes, but a consequence of other extrinsic causes, such as a reduction in lymphatic drainage.
VDR receptor competence induces recovery from CFS – Amy Proal (New York,USA) – has a working model of CFS in which a micorobiota of chronic pathogens accumulate a metagenome that is able to dysregulate the innate immune response, and cause the systemic inflammation characteristic of the disease. The process has been reversed using a VDR agonist (olmesartan medoxomil) and sub-inhibitory antibiotics.
A parent advocacy guide advising how to obtain educational services for children with neuroimmune disease – Laura Baker (Santa Barbara,USA) and Karla Rogers (Nevada City,USA) produced a comprehensive resource guide to assist parents meet their child’s educational needs.
Utilization of CFS continuing medical education courses – Hao Tian (Atlanta,USA) – this course was described and confirmed as an important online source for continuing medical education. There is a well utilized Primary Care course and one for allied health professionals. In a 5 month period, 283 participants received CME certificates.
The self-regulatory model in women with CFS and MS: illness representations, coping strategies and outcome - Elke van Hoof (Brussels,Belgium) – Patients were shown to determine the degree of dysfunction and illness related behaviours in relation to their subjective experience of the disease. Findings in the study will help determine what strategies may be effective in improving function.
Treatment study of methylation cycle support – Richard van Konynenburg (Springfield, USA) – Treatment designed to support the methylation cycle appears very promising and seems worthy of a more controlled study. Results are consistent with the glutathione depletion-methylation cycle block hypothesis for CFS. Treatment included hydroxocobalamin, 5-methyltetrahydrofolate and folinic acid, with nutritional support
Edited by uonderuoman - 8/6/2009, 10:56. -
uonderuoman.
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Il cervello utilizza piu energia rispetto a qualsiasi altro organo
Peters, A, Schweiger, U., Pellerin, L, Hubold, C., Oltmanns, K., Conrad, M., Schultes, B., Born, J and H. Fehm. 2004. The selfish brain: competition for energy resources. Neuroscience and Behavioral Reviews 28, 143-180
• While the peripheral organs can metabolize glucose, fat or proteins to produce energy, the restrictions the blood brain barrier (BBB) places leaves it almost exclusively dependent upon glucose. Since the brain has only a very limited ability to store energy it must ensure it receives a constant flow of glucose. In order to do this the brain constantly monitors its own energy levels and when necessary takes energy away from other parts of the body.
• The authors believe that reduced concentrations of ATP in the brain cause it to activate a stress program that increases its allocation of glucose from the periphery. At the same time it does this it activates the feeding centers of the brain and gives the signal to eat. The authors argue that the plasticity of the part of the brain involved in the stress response can cause it to produce dysfunctional set points at which this stress program is activated. Too high a ‘set point’ will cause the brain to continually pull glucose from the periphery and result in anorexia. Too low a set point will result in reduced brain energy levels, increased glucose levels in the periphery and obesity. The results of the Pharmacogenomics Allostatic Load papers suggest that the set point at which this stress response is induced is altered in CFS patients .
THE DETAILS
A Key Regulatory Element - Ion Channels The regulation of ATP concentrations in the brain plays a central role in this paradigm. ATP is the central agent of energy production (aerobic respiration) in the mitochondria. Glucose and fatty acids are the main fuels for ATP synthesis. The authors propose that ATP sensitive potassium channels (ion channels) found on neurons and neuroendocrine cells are a kind of 'energy sensor'. These channels are closed when ATP is abundant (high energy state) and open when ADP is (low energy state). Adenosine di-phosphate (ADP) is what is left over after a phosphate group from adenosine tri-phosphate (ATP) is removed. It is the release of the phosphate that provides energy. The ATP/ADP ratio in a cell determines, therefore, whether these ion channels are open or closed.
A Complication - The situation is actually more complicated than this. Both ATP and ADP bind to receptors on the ATP sensitive potassium channels called sulfonylurea receptors (SUR’s)
There are two types of SUR receptors on the ATP sensitive potassium channels; one has a high affinity for and one a low affinity for ATP.
High ATP affinity SUR receptors (SUR 1) – Cells with these receptors are active even when ATP levels are low. They are found throughout the brain on excitatory neurons – they serve to increase nervous system activity.
Low ATP affinity SUR receptors (SUR 2) – Because cells with these receptors become active only when ATP levels are high, they are inactive much of the time. These cells, not surprisingly, are mostly found on inhibitory neurons – they act to inhibit nervous system activity when it gets too high.
Given these traits the following scenario can be envisioned regarding the energy status of the brain.
• During pathologically low energy states neurons seek to save themselves by becoming unresponsive to outside stimuli. During these periods both excitatory and inhibitory neurons are inactive.
• During low but non-pathologic states of energy the excitatory neurons with high levels of high ATP SUR receptors are active but the inhibitory neurons are not. This results in increased glutamate production.
• During very high energy states the inhibitory neurons with low affinity ATP SUR receptors become activated in order to moderate nervous system activity. These neurons produce the neurotransmitter GABA.
Summing up: The key point is that the balance between nervous system excitation (glutamate production) and inhibition (GABA production) is determined by the ATP levels in the brain. If the brain needs more energy the excitatory neurons are activated and glutamate is produced. If the brain has too much energy the inhibitory neurons are activated and GABA is produced.
A side note - The receptors glutamate interacts with, called NMDA receptors, are found in the greatest abundance in three areas of the brain that are of great interest in CFS; the hippocampus, amygdala and basal ganglia. These regions are particularly vulnerable to a process called glutamic acid excitotoxicity which occurs when high glutamate levels damage or destroy neurons.
THE SELFISH BRAIN – increased glutamate production is the key element in the brain’s attempt to increase its energy levels. It does this in three ways; by robbing the periphery of glucose, by restricting glucose uptake by the tissues in the periphery, and by activating the feeding centers of the brain.
Robbing Peter to Pay Paul - Altering the Blood Brain Barrier – The first thing the brain usually does to get more energy is to rob the periphery of glucose. This occurs when glutamate produced by the neurons located near the blood brain barrier (BBB) causes the astrocytes lining it to produce glucose transporters (GLUT1) that increase the uptake of glucose from the blood into the brain.
Increasing Glucose Levels and Reducing Glucose Uptake in the Periphery – the brain also increases glucose levels in the bloodstream by prompting muscle and fat cells in the periphery to inhibit their uptake of glucose (and switch to another energy source). It does this through activation of the limbic-hypothalamus-pituitary-adrenal system (LHPA). This system, which links the two major stress response systems, the HPA axis and the sympathetic nervous system (SNS), originates in two regions of the limbic portion of the brain.
First, a description of how this process works. Neurons from the hippocampus and amygdala activate both the HPA axis and the SNS. HPA axis activation occurs via the production of neuropeptides (corticotrophin releasing hormone (CRG), vasopressin) that stimulate the pituitary to produce adrenocorticotropin (ACTH), which in turn triggers the release of the major glucocorticoid, cortisol, produced by the adrenal gland. Cortisol, an antagonist of insulin, increases blood glucose concentrations. Insulin is a hormone that promotes, among other things, glucose utilization.
SNS neurons project from the limbic region to the adrenal gland and pancreas where they respectively stimulate the release of epinephrine (adrenaline) and suppress insulin release. They also project to the muscles where they suppress glucose uptake.
Another way the brain can also increase glucose availability in the bloodstream is by using glutamate to trigger the feeding centers of the brain.
Summing Up: In a nutshell the authors believe that during states of low brain energy high affinity ATP sensitive potassium channels increase glutamate production, thereby (a) increasing glucose transport across the BBB into the brain, and (b) activating the stress response (LHPA) which impedes glucose uptake to the muscles and fat tissues, and (c) triggering the feeding centers of the brain.
A Final Step – This system contains one more layer of complexity. It is not a straight shot from stressor to LPHA activation. One doesn’t want a stress response of this magnitude to become activated at any kind of stress; one wants it to become activated only when really needed. The authors propose that the brain regulates the point or ‘set point’ at which the LPHA system is activated through two kinds of receptors, mineralocorticoid and glucocorticoid receptors (MR’s and GR’s) found on the neurons. The authors propose the brain regulates the ‘set point’ `at which the LPHA system becomes activated
These receptors operate in much the same way the ATP sensitive potassium channels do. Instead of reacting to ATP, however, they react to cortisol. Both are produced in the cell, and both regulate gene activity in the cell. The ability of the cell to adequately monitor its cortisol levels is key, therefore, to maintaining the proper energy levels in the brain.
MR’s and GR’s are known to regulate the transcription of many genes. One group of genes they interact with controls calcium ion channels, another group affects the activity of ligand gated ion channel (i.e. glutamate), and a third regulates intracellular signaling system involving G-protein coupled receptors. It is through these genes that MR/GR’s regulate the excitability of the limbic neurons and the activity of LHPA response. In this model then MRs/GRs are ultimately responsible for the stimulation/inhibition of the master hormone, cortisol.
• Mineralocorticoid receptors (MRs) – have a high affinity for cortisol; they bind to it even when low levels of intracellular cortisol are present. These receptors are excitatory, once bound they promote the production of more cortisol and other substances. If the MR's are too abundant or too active they will call for cortisol production when it is not needed. This will lead to an hyper-responsive stress response in which the brain constantly activates the HPA axis and SNS.
• Glucocorticoid receptors (GRs) – have a low affinity for cortisol; they bind to it only when intracellular cortisol levels are high. These receptors are inhibitory – they inhibit the production of cortisol and other substances. If these receptors dominate they will block the call for cortisol and lead to a hypocortisolic state. In this state the brain is not sufficiently responsive to its energy needs; it is locked in a hypo-responsive state.
Introducing Pathology – But where does the pathology occur? How do things go wrong with this system? One way this system can go wrong is via an alteration of the set point at which the brain’s stress response is activated. The is where the limbic region of the brain and the hippocampus comes in.
Peter's scenario posits that a chronically activated stress response can, through damage to the hippocampus (due to glutamate excesses?), alter the 'set point' as which the stress response of the brain kicks in.
Three Models of an Impaired Brain Response System - The authors describe three scenarios of altered LHPA set point activation. Not surprisingly given the connection between LHPA activation and glucose metabolism two of the three scenarios explain the genesis of abnormal feeding behaviors such as anorexia nervosa and obesity. These authors believe obesity and anorexia nervosa are brain diseases not behavioral problems.
Explaining Obesity – The first factor on the road to obesity is, as noted above, a stressor that dysregulates the set point of the LHPA system. It doesn’t appear to matter what kind of stressor – Peters invokes a psychological stressor in his example – but also states that low cerebral glucose levels, exercise, infection, a hypothalamic lesion, (low blood volume, hypoxia) or endocrine disrupting chemicals could have the same effects.
In Peters’ scenario a person undergoing a period of high psychological stress develops atypical depression. Atypical depression – the kind of mood disorder most often found in CFS – is characterized by lethargy, fatigue, overeating, increased sleep, avoidance of social contacts and low CRH and cortisol levels. (See Hypocortisolism – Artifact or Central Factor? for an alternative definition of ‘atypical depression’.)
Peters believes these findings are consistent with a decreased MR/GR ratio and a reduced set point of the LHPA system. In this scenario the brain is not selfish at all; it is in fact insufficiently selfish – it needs to pull more glucose from the periphery than it does. The low set point of the LHPA system results in extra allocations of glucose to the periphery and reduced allocations of glucose to the brain. This leads to fatigue, increased sleep and low cortisol levels.
The brain reacts to this by activating its feeding centers. This appears to be a process separate from the stress response - thus while the stress response is inhibited another part of the brain is still active - and telling the person to eat. Increased food intake increases glucose levels in the periphery and thus the brain but also results in increased mass in the periphery. Since more muscle and fat tissue results in greater glucose demand overall this scenario simply results in greater competition for glucose with the brain. This further stimulates the feeding response, etc - the person is continually beset by cravings for food and they get more and more obese. The impairment of the stress response stops the brain from doing what it should have been doing in the first place - increasing glucose transport across the BBB and reducing glucose uptake in the periphery.
Explaining anorexia nervosa - With regard to anorexia nervosa the opposite is true; the LHPA set point is too high. This increases glucose allocation to the brain but reduces it to the body. The low body mass indicates to the brain that it needn’t allocate much glucose to it. This results in the body wasting away without the brain activating the feeding response.
THE UNSELFISH BRAIN AND CFS - But how does all this relate to CFS? The authors of the two allostatic load papers in the Pharmacogenomic's Journal proposed that a stress induced dysregulation of the LHPA system has resulted in an abnormally low LHPA ‘set point’ in CFS. Their study indicated that the levels of two substances (aldosterone, cortisol) that bind to the MR and GR receptors were much lower in CFS patients than in the non-fatigued controls. This suggests a central metabolic dysregulation exists in CFS. The high rates of obesity in the CFS patients, and, in particular, the increased waist/hip ratios do, in fact, suggest a central metabolic dysregulation is present. In this scenario the brains are selfish enough; the low set point in the brain precludes their brains from pulling enough glucose from the body. Low cerebral glucose levels have been found in CFS.
Maloney et. al. posit that a stressful event (psychological stress, infection, toxin, low blood volume, hypoxia) has lowered the set point of the brains stress response system. This has lead to an increased allostatic load not just with regard to CFS patients metabolism but in their cardiovascular system as well, and would, of course, have many other affects on the body.
Limbic System
(adapted from Stedman’s Electronic Medical Dict.)
The limbic system describes an array of different brain structures including the hippocampus, amygdala, and fornicate gyrus, all of which connect to the hypothalamus. Through its connections with the hypothalamus the limbic system exerts an important influence upon the endocrine and autonomic motor systems; its functions also appear to affect motivation and mood.
The HIPPOCAMPUS - A Locus of Dysregulation?
The stress response had long been thought to stop at the gateway between the brain and the endocrine system, the hypothalamus. Recent evidence indicating that the hippocampus contains high levels of receptors for adrenal hormones indicates that it too is activated during the stress response. Peters et. al. believe that the impact of stressful events on the hippocampus can cause it to permanently alter the LHPA activation set point in some people.
What makes this theory plausible is the high degree of plasticity the hippocampus displays. The hippocampus needs to display a high degree of plasticity because it appears to be the seat of an important process called long-term potentiation (LTP). LTP is involved in our ability to apply lessons learned from an experience to similar experiences in the future. Experiments with laboratory animals suggest this type of learning may be centered in the hippocampus. The amygdala and hippocampus appear to decide what is stressful and how to deal with it.
Just as with the immune system short term elevations of epinephrine and cortisol appear to promote hippocampal functioning and learning but chronic elevations lead to impaired functioning. The hippocampus appears to respond to chronic stress with atrophy, memory impairment and increased fear. A dysregulation centered in the hippocampus by an infection, trauma, psychological stress, low blood volume, etc could lead to an over or underactive response to all sorts of stimuli ranging from infection to low blood glucose levels to low blood volume etc
___________________________
McEwen, B. Plasticity of the hippocampus: adaptation to chronic stress and allostatic load. Annals New York Academy Science, 265-277.
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uonderuoman.
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http://www.ncf-net.org/forum/JustAsk-S07.htm
Q: I have been diagnosed with CFS. My doctor wants to put me on IVIG. Is there any information in the medical literature that you may be aware of regarding its use for this disease? (Internet question)
A: For those who may not be familiar with the terminology, IVIG is intravenous immunoglobulin. IVIG is a blood product that contains the pooled IgG immunoglobulins which are antibodies extracted from the plasma of blood donors. Now, to answer your question, there is information in the medical literature. Let me expand on this as best as I can. CFIDS/ME patients have been found to have diminished amounts immunoglobulins
and in fact, subclass deficiencies (IgG1 and IgG3), have been seen [1 - 6]. As such, immunoglobulin replacement may be helpful to some patients [7 - 10]. I suggest you take these references to your physician and once they have reviewed this material with you, then perhaps you can make an informed decision regarding treatment. This may take on additional significance in light of the CD19 B-cell abnormalities that were found in patients. This research was recently published [11] and it was further highlighed by the NCF [12].
1. Immunologic abnormalities in chronic fatigue syndrome; Klimas NG, Salvato FR,
Morgan R, Fletcher MA; J Clin Microbiol. 1990 Jun;28(6):1403-10
2. Immunological abnormalities in the chronic fatigue syndrome; Lloyd AR, Wakefield D,
Boughton CR, Dwyer JM; Med J Aust. 1989 Aug 7;151(3):122-4
3. IgG1 subclass deficiency in patients with chronic fatigue syndrome; Read R, Spickett G,
Harvey J, Edwards AJ, Larson HE; Lancet. 1988 Jan 30;1(8579):241-2
4. Immunoglobulin subclass abnormalities in patients with chronic fatigue syndrome;
Wakefield D, Lloyd A, Brockman A; Pediatr Infect Dis J. 1990 Aug;9(8 Suppl):S50-3
5. IgG subclass deficiencies in chronic fatigue syndrome; Komaroff AL, Geiger AM,
Wormsely S; Lancet. 1988 Jun 4;1(8597):1288-9
6. IgG subclass deficiency and chronic fatigue syndrome; Linde A, Hammarstrom L,
Smith CI; Lancet. 1988 Apr 16;1(8590):885-6
7. A double-blind, placebo-controlled trial of intravenous immunoglobulin therapy
in patients with chronic fatigue syndrome; Lloyd A, Hickie I, Wakefield D, Boughton C,
Dwyer J; Am J Med. 1990 Nov;89(5):561-8
8. A controlled trial of intravenous immunoglobulin G in chronic fatigue syndrome;
Peterson PK, Shepard J, Macres M, Schenck C, Crosson J, Rechtman D, Lurie N;
Am J Med. 1990 Nov;89(5):554-60
9. Double-blind randomized controlled trial to assess the efficacy of intravenous
gammaglobulin for the management of chronic fatigue syndrome in adolescents;
Rowe KS; J Psychiatr Res. 1997 Jan-Feb;31(1):133-47
10. Intravenous immunoglobulin treatment for the chronic fatigue syndrome; Straus SE;
Am J Med. 1990 Nov;89(5):551-3
11. Clinical activity of folinic acid in patients with chronic fatigue syndrome; Lundell K,
Qazi S, Eddy L, Uckun FM; Arzneimittelforschung. 2006;56(6):399-404
12. It Is What It Is: Searching for Truth; The NCF's report on important keynote medical
discrepancies regarding a severe B-cell immunodeficiency in CFIDS/ME patients; 2006
Q: I heard rumors over the internet that the NCF had interests in folinic acid as a possible treatment option. Can you share any information with the patient community? (Internet question)
A: This is true. Several patients associated with the NCF went on folinic acid at a 5 mg dosage, three times per day for several months. Each patient was under physician care. Before the volunteer patients began any treatment, their physicians did complete lymphocyte profiles. These included absolute and percentage cell counts for CD3 (total lymphocytes), CD4 (helper T-cells), CD8 (cytotoxic/suppressor T-cells) and CD19 (B-cells). Then these patients went on therapy as outlined above for several months. At completion, these lymphocyte profiles were run again on each patient. We were certainly interested in the biological mechanism of folinic acid and what potential effects that it may have on these patients in light of the paper published by Dr. Uckun. We learned that the Chairman/CEO of EpiGenesis Pharmaceuticals had discovered that folinic acid is used to treat adenosine depletion. The other thing we came to realize is that we observed immune modulation that appeared to be represented, at least in our patients, by a reduction in some of the CD4 T-cell counts. Please keep in mind that this was an observation and not some double-blinded trial with age and sex matched controls. This information is very intriguing considering that some CFIDS/ME patients go on to develop Idiopathic CD4 Lymphocytopenia (ICL) which has been seen in HIV-negative AIDS patients as reported in the medical literature [1 - 4]. ICL itself has been associated with a deficiency of adenosine deaminase [1]. Technically speaking, adenosine deaminase deficiency causes an increase of dATP, which inhibits S-adenosyl-homocysteine hydrolase, causing an increase in S-adenosylhomocysteine. Both dATP and S-adenosylhomocysteine have toxic affects on lymphocytes, causing them to be functionally defective. The defective function is caused by a depletion of all of the dNTP pools. This causes a breakdown in DNA synthesis and repair of breaks occurring in the DNA. This makes for a very serious disease and that is why the presence of ICL in CFIDS/ME patients causes a severe immunodeficiency where patients become prone to repeated infections. In CFIDS/ME, this is an acquired condition due to the disease progression itself. I should point out that one treatment option for adenosine deaminase deficiency involves the replacement of the enzyme adenosine deaminase itself. The drug used for this is called Adagen by Enzon Pharmaceuticals and it has been used for the treatment of severe combined immunodeficiency disease, known also as SCID, due to adenosine deaminase deficiency.
1. Adenosine deaminase (ADA) deficiency as the unexpected cause of CD4+ T-lympho-
cytopenia in two HIV-negative adult female siblings; Fairbanks LD, Simmonds HA,
Webster AD, Shovlin CL, Hughes JM; Adv Exp Med Biol. 1994;370:471-4
2. Idiopathic CD4+ T-lymphocytopenia--immunodeficiency without evidence of HIV
infection; Ho DD, Cao Y, Zhu T, Farthing C, Wang N, Gu G, Schooley RT, Daar ES;
N Engl J Med. 1993 Feb 11;328(6):380-5
3. Unexplained opportunistic infections and CD4+ T-lymphocytopenia without HIV
infection. An investigation of cases in the United States. The Centers for Disease Control
Idiopathic CD4+ T-lymphocytopenia Task Force; Smith DK, Neal JJ, Holmberg SD;
N Engl J Med. 1993 Feb 11;328(6):373-9
4. Acquired T cell specific deficiency other than acquired immunodeficiency syndrome (AIDS);
Saiki O, Ogawa H, Ikeda T, Masuno T, Tanaka T, Deguchi Y, Endou T, Kishimoto S;
Intern Med. 1992 Jan;31(1):11-6
Q: At the recent IACFS Conference held in Fort Lauderdale, were there any research reports that stood out to the NCF researchers? (Internet question)
A: There was a research presentation from Dr. Rokutan, who is from Japan, on the "Application of a DNA chip for Fatigue Assessment." Though the study involved a small number of patient samples (11), several of the genes that were noted to be modulated included several that play an important role in the microenvironment of the bone marrow. One of the genes that was found to be altered in this study was Stat-5. A quick check of the medical literature from Pubmed reveals that Stat5 plays a critical role in the replication capability of stem cells.
This is a very significant finding due to the fact that all cells in the human body are derived from stem cells and if there is a problem that is occurring at this level of the cell in the bone marrow itself, then this provides a significant clue as to what is occurring. These concepts will be discussed in a future Forum. As noted above in this column, patients and physicians who choose to discount the findings and to downplay the importance of Dr. Uckun's research will do so at their own peril.
The National CFIDS Foundation
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nononeurona.
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anestesia e cfids
CFIDS and anesthesia: what are the risks?
By Elisabeth A. Crean
www.cfids.org/archives/2000/2000-1-article03.asp
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gulio.
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Apo?
Siamo arretrati un bel pò.
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