Special Message for you from Ron Davis (video)

percyval577

geometrical disaster
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Thank you for your answere, @Pyrrhus. And it´s alway helpful when somebody with professional knowledge (as it seems in your case) does a commentary. Well, my doctors... I am particular interested here because I like to have figured out a Mn + ARG impact, pathway and reverse (so, I am increasingly happy). The second impact, EBV, might have worked also via Mn somehow, theoretically and to keep it simple.

However, Naito et al say at least: "... that arginine does not directly interfere with the formation of progeny infectious virus." which allowed for the interpretation that arginine would elevate NO production in host cells, like in the 2003 study. If there have been any in the 2009 trial.
Nevertheless, I personally ask me now, if it could be, that if hadn´t eaten meat when I had my acute EBV infection, that I wouldn´t have gotten so many problems. Next time I will double up myself, being n=2.

I don’t know about any further research that looked into differential amino acid utilization by RNA viruses. I would certainly be interested in any such research.
EBV is not an RNA virus, but the following paper is on its mRNA. Though, it might well be very unlikely that this would be a conservative region and would be an explanation for an anti-Naito outcome. [And once more unlikely that there would have been an inverse non-arginine-rich motif in a DNA, and the DNA would have evoleved from a (non-mirrored) RNA.]
A Region of the EBV mRNA Export Factor EB2 Containing an Arginine-rich Motif Mediates Direct Binding to RNA Hiriart et al 2003

I have partly read the paper but cannot recall. The title says it already I guess.


Edited for brain fog.
 
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FMMM1

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Thank you for your question.

Regarding herpesviruses, the general understanding is as described in this 1981 review:


As you mention, work by Naito seems to contradict the general understanding, as described in this 2009 paper:


I don’t know how to reconcile the two general findings. It may be that herpesviruses require an ideal concentration of arginine, and either too much or too little slows down viral replication.

Naito also described experiments on 3 different RNA viruses, which did not show any strong effect of excess arginine:


I don’t know about any further research that looked into differential amino acid utilization by RNA viruses. I would certainly be interested in any such research.

Hope this helps.
Certainly the mitochondrial fragmentation Bupresh Prusty demonstrated in ME can be caused by a virus, data presented by Bupresh at last months NIH Conference, i.e. showed that the supernatent from HHV-6A infected cells also fragment mitochondria. However, we don't know how common mitochondrial fragmentation is in ME e.g. 30% --%. Also, Bupresh suggested that it is likely that bacteria also use mitochondrial fragmentation to evade the immune system. So I assume we're currently not clear regarding the role of virus's - although I think that Bupresh's data suggests they may be causal.
 
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@Pyrrhus
Do you know anything about the possibility of enteroviruses "hiding out" in skeletal muscle fibers? I could go searching PubMed, but figured you might know off the top of your head. Or anyone on this forum.
Muscle cells are post-mitotic and so rarely lyse. We mostly have the same muscle cells we were born with.
thanks!
 
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Do you know anything about the possibility of enteroviruses "hiding out" in skeletal muscle fibers? I could go searching PubMed, but figured you might know off the top of your head. Or anyone on this forum.
Muscle cells are post-mitotic and so rarely lyse. We mostly have the same muscle cells we were born with.
thanks!
@skandar here is a 2005 paper discussing the conflicting findings of enterovirus in muscle.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1770761/

Also @Hip had a good post discussing some of the issues with enterovirus history and ME/cfs on s4me
https://www.s4me.info/threads/why-h...me-cfs-jen-brea-asking.4967/page-2#post-89342
 

Pyrrhus

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@Pyrrhus
Do you know anything about the possibility of enteroviruses "hiding out" in skeletal muscle fibers? I could go searching PubMed, but figured you might know off the top of your head. Or anyone on this forum.
Muscle cells are post-mitotic and so rarely lyse. We mostly have the same muscle cells we were born with.
thanks!
Thank you for your question. I’m glad @Hip pointed you towards that excellent MEpedia article.

Yes, muscle cells are terminally differentiated and therefore do not divide to form new muscle cells. But the immune system can, in theory, remove infected muscle cells, and the removed muscle cells are replaced by myosatellite stem cells which can differentiate into new muscle cells.

But it takes time for infected muscle cells to be removed and replaced. In the meantime, the muscle tissue can be re-infected with virus from the motor neurons that are activated when the muscle is contracted. In this case the virus persists in the ganglia of the spinal cord and may travel from the spinal cord through the motor neuron to the muscle, a process that can take a day or so.

Hope this helps.
 
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Thank you for your question. I’m glad @Hip pointed you towards that excellent MEpedia article.
But it takes time for infected muscle cells to be removed and replaced. In the meantime, the muscle tissue can be re-infected with virus from the motor neurons that are activated when the muscle is contracted. In this case the virus persists in the ganglia of the spinal cord and may travel from the spinal cord through the motor neuron to the muscle, a process that can take a day or so.
Thanks @Pyrrhus
I know a good deal about muscle, but almost nothing about viruses, and I didn’t know if some viruses that can’t be found in the blood could be evading detection in muscle, as I think may be the case in neurons. People make reference to enteroviruses in neurons for instance, and since they don’t proliferate or undergo apoptosis, a virus living there would be hard to find in blood.
I did not know that a virus could travel down an alpha motor neuron and be released from the motor end plate and infect a muscle fiber
Interesting!
 

Pyrrhus

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People make reference to enteroviruses in neurons for instance, and since they don’t proliferate or undergo apoptosis, a virus living there would be hard to find in blood.
The most widely cited example of this is with poliovirus, the best studied enterovirus. In the first few days after infection, virus can be easily found in blood, while no symptoms are apparent. About a week after infection, neurological symptoms may develop, at which point virus can no longer be found in the blood.

A new slide from yesterday you or others might be interested to see
Thanks for sharing that. The relevant part of the slide is point #4, which says that they are still trying to develop a method to look for RNA viruses such as enteroviruses. Even if they succeed in developing such a test, I would not expect to find any enteroviruses in the blood.

Cheers!
 
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@Pyrrhus This is very helpful. Thank you.
Yes #4 will be important and I suspect u are correct from what you and Ron D have talked about. For any virus it seems essential to first get rid of human DNA/RNA in the blood, then sequence everything leftover using HTS (NGS) so there is no bias and they don’t use filters to get rid of repeat sequences when they do analysis.
 

Pyrrhus

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Would you mind sharing the documentation on this?
In this 2008 review of Arbidol, the authors state that the drug works by blocking viral (virion) entry into cells:
https://pubmed.ncbi.nlm.nih.gov/18393857/

In the acute phase of enteroviral infection, the virus spreads in the body in the standard virion form. A virus in a cell replicates itself into new virions, the virions exit the cell, and then the virions enter other cells. Thus, a drug that blocks viral entry would prevent a virion from entering a new cell.

In the persistent phase of enteroviral infection, however, the virus likes to hide inside nerve cells. Instead of creating new virions and exiting the nerve cell, the virus lazily takes advantage of the network of nerve cells to spread from nerve cell to nerve cell directly, without creating virions. Thus, a drug that blocks virion entry would be useless in this persistent phase of infection.

The only study I could find that demonstrated activity of Arbidol against enterovirus only looked at the acute phase of the infection:
https://link.springer.com/article/10.1007/s00705-009-0346-4
(The drug was administered to the mice only 24 hours after infection.)

Hope this helps.
 

sometexan84

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In this 2008 review of Arbidol, the authors state that the drug works by blocking viral (virion) entry into cells:
Thank you.

I've been looking into Coxsackie B4 options. So, maybe this is referring to B5 or something else. Maybe that study was referencing a totally different set of virus altogether?

But it appears Umifenovir has the potential to inhibit persistent CVB4 replication altogether.

https://me-pedia.org/wiki/Umifenovir
"umifenovir inhibited Coxsackie B4 in part by reducing the expression of IL-10 (by preventing p38-MK2 complex from exiting the nucleus)"

(2017) Umifenovir effectively inhibits IL-10 dependent persistent Coxsackie B4 virus infection

Thoughts?
 

Pyrrhus

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But it appears Umifenovir has the potential to inhibit persistent CVB4 replication altogether.
Possibly. I just found a 2014 review article by the authors of the 2008 review article. Now, it seems, they are backing away from their claim that Arbidol/Umifenovir works by blocking viral entry into cells. Now they say that the drug can have lots of different effects, and they're not really sure which ones are responsible:
https://www.sciencedirect.com/science/article/pii/S0166354214001120

So, ¯\_(ツ)_/¯ !

P.S. By the way, when you read articles that refer to "persistent" infections, it helps to ask if the article is talking about in vitro infections, or in vivo infections. Mechanisms of persistence in vitro can be quite different from mechanisms of persistence in vivo.
 
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@Pyrrhus

Hello! Thank you for your scientific expertise, from which we all can draw a benefit. You have mentioned that Arbidol is only effective for fighting an acute Coxsackie infection. Later on, your referred to a source that leaves it open whether or not Arbidol only works for an acute infection (the authors do not know precisely).

I remember reading Dr. Lerner's theory according to which a patient should take valacyclovir for a long time in order to tackle a chronic EBV infection. Sticking to his theory, the levels of valacyclovir in the blood stream must be high to reach the cells in which EBV is persistently living/existing.

I am not a doctor but a layperson. Nevertheless I could imagine the above mechanism might work for Arbidol and Coxsackie as well. Let me quote from your explanation, please:


"Yes, muscle cells are terminally differentiated and therefore do not divide to form new muscle cells. But the immune system can, in theory, remove infected muscle cells, and the removed muscle cells are replaced by myosatellite stem cells which can differentiate into new muscle cells.

But it takes time for infected muscle cells to be removed and replaced. In the meantime, the muscle tissue can be re-infected with virus from the motor neurons that are activated when the muscle is contracted. In this case the virus persists in the ganglia of the spinal cord and may travel from the spinal cord through the motor neuron to the muscle, a process that can take a day or so."


Following that mechanism, I think that Arbidol could be beneficial for fighting a chronic Coxsackievirus infection since a further spread of the virus would be blocked by the effect of Arbidol. Easily put, when a virus can't spread anymore, it stops existing in the course of time as every human cell dies with time.

What do you think?

I have taken Arbidol for some days now and am curious about how I will feel in the future. I will post my health status.

Best wishes and all the very best to all of you!

Johnny Minnesota
 

Ben H

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i dont know why the Open medicine foundation continues to ignore our messages. our open letters to the open medicine foundation. mine is just one, there are many now https://openletteropenmedicinefoundation.com
Hi @debored13 ,

I'm just a volunteer advocate, but I have passed this on to OMF. I'm not sure what has happened here- OMF are usually very good at responding to messages. Ron gets a ridiculous amount of messages, but he doesn't ignore patients (which I think is evident from the amount of patient input that has been shown via videos, questions and through @Janet Dafoe and myself) even if he doesn't have the time for a direct response (I'm not saying that's what's happened, I'm just saying!).


Take care,

Ben