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If the viruses that are thought to cause ME/CFS are communicable (which they are), then that means the disease is also communicable.
This is false.
We need to be specific otherwise people will misunderstand the disease.
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Created in 2008, Phoenix Rising is the largest and oldest forum dedicated to furthering the understanding of, and finding treatments for, complex chronic illnesses such as chronic fatigue syndrome (ME/CFS), fibromyalgia, long COVID, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and allied diseases.
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If the viruses that are thought to cause ME/CFS are communicable (which they are), then that means the disease is also communicable.
This is false.
We need to be specific otherwise people will misunderstand the disease.
Prof Paul Ewald posits that most chronic diseases of currently unknown etiology will turn out to be caused by infectious pathogens. This includes diseases such as multiple sclerosis, Parkinson's, heart disease, diabetes, cancers, etc. In the case of MS, we know this is linked to EBV, and in particular, to specific genetic subtypes of EBV.
I am not saying Prof Ewald is wrong. I have heard other scientists argue that if the disease is chronic then its cause must be chronically present. Metabolic traps are just an alternative hypothesis. Traps are interesting because they do not require a chronic cause. A transient trigger is all you need.
To me, there is an important difference between the trigger of the disease and the cause of the disease.
it's very difficult to explain all the cases of ME/CFS that do not begin with an infection - the ones beginning with trauma, or surgery, or overtraining,
We are, I think, both saying that ME/CFS is not infectious. You can meet and marry someone who has ME/CFS and not fear contracting this illness.
but if he means that these diseases are caused by a chronic infection with these pathogens, then it's difficult to explain why someone has not isolated non-human RNA or DNA from ME/CFS patients who have been sick for years.
Why does the body fail to heal - fail to cure itself - how did a person make it through childhood and often through young adulthood and suddenly encounter an infection the immune system cannot handle?
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If Prof Ewald means that chronic diseases of unknown etiology will be found to be triggered by infectious pathogens, then I would have no argument, but if he means that these diseases are caused by a chronic infection with these pathogens, then it's difficult to explain why someone has not isolated non-human RNA or DNA from ME/CFS patients who have been sick for years. Of course, absence of evidence is not evidence of absence, so if tomorrow someone isolates a causal RNA or DNA virus from ME/CFS patients who have been sick for decades, stimulates the immune system to clear it, and cures this horrific disease, I'm going to celebrate along with everyone else. But techniques for isolating hon-human RNA and DNA are now extremely powerful and there is as yet no candidate virus to be followed up.
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Wouldn't it be great if this adage was taught in medical school?Of course, absence of evidence is not evidence of absence
does anyone know what happens to serotonin and melatonin as a result of this trytophan based metabolic trap (as opposed to the tyrosine one)....?
In turn, increased cytosolic tryptophan will drive excessive serotonin production in cells, like serotonergic raphe neurons, that express TPH2 (human chromosome 12) [50] with its normal Michaelis-Menten kinetics [51], or may result in decreased serotonin and melatonin production in cells, such as antigen presenting cells, enterochromaffin cells, and pinealocytes that express the classical “peripheral” tryptophan hydroxylase, TPH1 (human chromosome 11) [50]. This is because TPH1 is, itself, substrate inhibited at high concentrations of its substrate, tryptophan [51,52].
Even if serotonin and melatonin production are unperturbed, the absence of kynurenine and its metabolites can have untoward effects. For example, kynurenine is spontaneously converted to trace condensation products called TEACOPs that are potent activators of the aryl hydrocarbon receptor (AHR), a transcription factor that controls the development of Treg cells [53].
does anyone know what happens to serotonin and melatonin as a result of this trytophan based metabolic trap (as opposed to the tyrosine one)....?
@Snow Leopard answers this question with a quote from our paper that's right on target. I would just add that these are predictions are based on enzyme kinetic theory, not on experimental data.
Also, the dependence on cell type has consequences for testing the IDO trap hypothesis. If one cell type is in the IDO metabolic trap, this does not prove that all cell types are in the trap. Conversely, if one cell type is not in the trap, we can't conclude that all cell types are "trapless."
this is weird, I actually have low serotonin as measured in the platelets... platelets are know to collect serotonin from the blood across the whole body and store it inside themselves. Could a serotonin overload actually disrupt the ability of said platelets to collect serotonin causing an opossite effect to what would be expected in this case?
thanks for the info! do you remember where could you have read that? on a side note, clomipramina, that also acts increasing serotonin concentration in the synaptic cleft, relieves my pain from disc herniations (I've got 4 of them)I believe I read that the trap, if true, could cause higher serotonin in some places, and lower in others.
I’m assuming this explains why an SNRI removes 95% of my chronic pain. That is, the SNRI increases serotonin in my area of need.
Just a guess...
As I understand, this drug increases tryptophan content on the brain while releasing it from storage on the liver... It seems to be something that could be useful for ocd, depression, etc, but I don't see how it could help with this metabolic trap. What do you think?A poster on a facebook forum posted this study showing the old drug Disulfiram has an effect on tryptophan. Significance?
https://www.ncbi.nlm.nih.gov/pubmed...VS_60RFb8Ywf2l16XGvyjfdVVQt-c65CaDLAtCqlXWftA
Effect of disulfiram administration on brain tryptophan, serotonin and peripheral tryptophan content.
Nagendra SN1, Shetty KT, Subhash MN, Udaya HB, Pradhan N.
Author information
1Department of Neurochemistry, Psychopharmacology, National Institute of Mental Health and Neuro Sciences, Bangalore, India.
Abstract
The prophylactic deterrent effect of disulfiram (DS) has been attributed to its ability to exacerbate sympathetic function. Though there are reports to indicate that DS administration could as well affect the neurotransmitter metabolism, few reports implicate the possibility of central nervous system (CNS) mediated anticraving effect of the drug. The present study involving the oral administration of DS to rats for 45 days has clearly shown a significant increase in 5-HT (815.4 +/- 74.7 ng/g, P < 0.01) and 5-HIAA (506.1 +/- 86.3 ng/g, P < 0.02) contents in brain when compared to control rats. The observed increase in 5-HT and 5-HIAA content was found to correlate (zeta = 0.89) with the concomitant increase in brain tryptophan content (4.15 +/- 1.05 nmol/g, P < 0.001) following DS administration. Further, the study on peripheral tryptophan content has shown an increase in both total and free fraction (ultrafiltrate) of plasma, which in turn was found to have an inverse relationship (zeta = -0.94, P < 0.05) with the decrease in liver tryptophan content following DS administration. Thus the observed increase in brain 5-HT level is attributed to the ability of DS to mobilise peripheral tryptophan for 5-HT synthesis in CNS. As there are reports to imply the hyposerotonergic function as responsible for craving, the present findings, that DS could enhance the 5-HT metabolism in brain, may partially explain the CNS mediated anticraving effect of DS.
As I understand, this drug increases tryptophan content on the brain while releasing it from storage on the liver... It seems to be something that could be useful for ocd, depression, etc, but I don't see how it could help with this metabolic trap. What do you think?
It certainly will! by the way, do you know if they're any plans to perform a new nanoneedle study with more patients and controls? I was wondering thatDisulfiram is gaining a lot of traction in Lyme disease forums. I wonder if this could be worth testing in the nanoneedle.