Discussion in 'General ME/CFS Discussion' started by Jonathan Edwards, Aug 10, 2014.
Yep. here it is :
After looking at your source, I note that these timescales relate to a mouse 'model' of 'depressive-like symptoms'.
Here is a quote:
The 'forced swim test' involves putting animals in water until they give up trying to stop themselves from drowning, due to exhaustion and/or despair. If LPS etc. make this happen sooner, it could be from either. I would guess that it is more likely exhaustion. Animals have an enormous drive to survive. We know how exhausted we feel with PEM, and I am always physically weaker then. It's not depression or despair.
But I am sure this could all be worked out by going straight to humans rather than torturing animals.
Cruelty and questionable basic relevance of such 'models' aside, the timescales are very unlikely to be the same in humans from my knowledge of general species differences.
@taniaaust1 Is it possible that you'd achieve the same results you want from IV saline by using either footbaths or enemas to deliver sodium? I was only once hospitalized for IV saline, due to a detox crisis. Following that I added to footbaths, and increased the amount that I'd been adding to my enemas.
Yeah, exertion in general is not easy on the gut, if it's sensitive or leaky even more-so. But in turn it reduces your appetite and eating frequency, which I think is key to treating leaky gut as well as SIBO. Eat 2-3 times a day, not more and allow 5-7 hours (or more) in between meals for the gut to cleanse and repair itself (which it usually doesn't if not mostly empty).
I was just wondering whether the different MEs would have any prognostic value. Which of the groups would be most likely to lead to severe ME?
Voner found it somewhere else.
Thanks Prof. Edwards. FYI, your paper is freely available here: http://onlinelibrary.wiley.com/doi/10.1046/j.1365-2567.1999.00772.x/full
What I know as the cell stress response has been around for decades. Some cells have additional specific danger response mechanisms like Toll-like receptors. It is a large amorphous area of metabolic responses. I am afraid that any paper that says 'An understanding of the CDR permits us to reframe old concepts of pathogenesis for a broad array of chronic, developmental, autoimmune, and degenerative disorders. ' I immediately assume to be drivel probably written by some junior researcher wanting to get grants in for their attempt to follow fashion. Science is more measured and more specific than that to my mind! I like to have a precise story for each disease and each disease is different from all the others in a different way. The broad brush approach spells naivety to me!
Now that's pretty unequivocal as an opinion I guess! Maybe I should be more detailed... but...
I am not sure that will be helpful. I suspect all of them can be on a spectrum from mild to severe. If some are mostly mild they will not get noticed so the profile that does get noticed for that group will seem just as severe as the others - I think it ends up not answering anybody's personal question I fear. And that is what matters.
Thanks for that, I look forward to reading it later in the week....
It would answer a personal question of mine. Which is: ‘How much worse can this get?’
Thank you for replying.
Does this look like that?
That does look impressive! I think I will look at the paper again.
I did not want to respond to the question until you did! I read the post in light of my special interest: energy generation. The author describes purines such as AMP and Adenosine as being 'sigalling' when the cell is in distress. While AMP is commonly used during the cells internal response to hormones as a signalling molecule it also occur in two situations that have nothing to do with signalling.
Firstly where mitochondria are failing to generate energy (e.g. during hypoxia or true dysfunction) a 'rescue process' generates ATP at expense of producing more AMP that is then converted to Adenosine in order to to remove it from the cell - this in turn stimulates local vasodilation in order improve oxygen supply. One thus ends up with AMP inside the cell, and Adenosine in the blood stream.
Secondly when the cell is in enough distress the nucleus instigates cell death, thus producing these molecules thorough deliberate impairment of mito function.
This more as a 'consequence of cellular stress' rather than as the paper implies a 'defensive mechanism'.
@Jonathan Edwards Persistent EBV appears to be strongly associated with many cases of ME and Prof. Michael Pender believes that the T cell specific immunotherapy technique he has developed, could work for other autoimmune diseases as it does for Primary Progressive M.S. http://multiple-sclerosis-research.blogspot.co.uk/2014/02/guest-post-professor-michael-pender.html
Carmen Scheibenbogen has also demonstrated PwME having an impaired immune response to EBV http://www.plosone.org/article/info:doi/10.1371/journal.pone.0085387
Do you agree that EBV plays a role and if so, how does that feed into your subgrouping?
Might there be subgroups for which this kind of T cell immunotherapy wouldn't be successful ?
I think we need to get the context right here. Remember that almost everyone has persistent EBV infection of B cells. It is the normal situation for at least 90% of human beings. The piece on Dr Pender's theory looks to me naive. I have never heard of this theory and frankly it does not make much sense, since all our B cells contain EBV DNA. The case report he gives tells us nothing I am afraid. His ideas about rheumatoid arthritis similarly do not seem to make sense since EBV DNA is everywhere in all of us.
Carmen Scheibenbogen has done some extremely interesting work on altered EBV serology in CFS patients. I do not think one can call this an impaired response, because we do not know its significance. it might be a 'better' response for all we know. But the fact that it is different certainly suggests that B cell regulation may be shifted in some way. It may be shifted for responses to all sorts of other things. I don't think we know. At least it is another piece of evidence for a change in B cell behaviour.
I do not think any of this indicates that 'EBV plays a role'. Since we all have EBV it is hard to say it is the cause of ME in PWME when other people have EBV and no ME. What is a more interesting question is whether the causation of some ME needs EBV to keep itself going. If it does then eradicating EBV would make sense. However, Dr Pender's idea that rituximab produces improvement by eradicating EBV must I think be nonsense because of the time frame of response - as we have discussed before. What is conceivable is that in those who stay well the absence of EBV contributes to that. The question then is why the other people relapse if their EBV is cleared as well?
I cannot see much point in T cell immunotherapy if we can get rid of the B cells with rituximab much more effectively!!!
The paper reported increased latent replication of EBV, lower cytokine response against EBV, and reduced number of EBV antibody producing cells. I'm all for being cautious to make hasty conclusions, but it seems very unlikely to me (as amateur) that this could be a positive adaption (or mere chance).
I hope these findings are replicated soon.
It also fits with Rituximab, and mononucleosis often triggering CFS.
I would have to agree... Forced swims also have no relation to ME, they monitor the response of a healthy animal (or human) to irrational over exertion. I really cannot see the scientific validity of the test... That's before I even start on the ethics....
Unless I have missed a post, the point of the IV saline was not sodium but water. The objective being to increase blood volume and normalise her bodies regulation of blood pressure.
Or have I missed something?
You said exertion reduces appetite, could you clarify how and why please? It's new information to me so, I am curious....
Which paper caught your eye Lansbergen... ??
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