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Ebola: Discussion of Treatments

Re: Ebola: Discussion

Re: Ebola: Discussion

The best summary of evidence and limitations for Vitamin C functions and requirements I can find is presented here.

http://lpi.oregonstate.edu/infocenter/vitamins/vitaminC/

and with specific reference to immune system function

http://lpi.oregonstate.edu/infocenter/immunity.html

As Vitamin C has a fairly short halflife (30 minutes) and is involved in immune system response, there is some logic that requirements will be increased during ill health and acute infection, and that deficiency could increase the propensity for damage to blood vessel walls.

However, the disease aetiology of ebola is very much more complex than this. The major problem is immune system dysregulation and a cytokine storm, and a propensity for the virus to attack epithelial cells, leading to the development of leaky blood vessels.

At best, you could argue for Vitamin C as part of supportive nutritional therapy during an infection (probably wouldn't do any harm) but given how ebola works, I cant see (even on a theoretical basis) that it would make more than a marginal difference to the clinical course or disease outcomes in an infected person.
 
Re: Ebola: Discussion

Re: Ebola: Discussion

Here's where I think someone might get the idea that vitamin C is consumed by ebola - "the parallels between the clinical features of sepsis and its sequelae and Ebola hemorrhagic fever (EHF) are striking" and the following article on sepsis discusses sepsis vit C metabolism:

Evolving strategies in the treatment of sepsis and systemic inflammatory response syndrome (SIRS)

Search for "Ascorbic acid (vitamin C) loading" in the PDF. But it also mentions that vit C can have pro-oxidant effects and that they've actually seen benefits in sepsis from vit E usage, rather than vit C. Vit E also reduces monocyte tissue factor expression in cirrhotic patients and over-expressed TF might play into ebola complications.

Another caveat about vit C usage in ebola might be:

Vitamin C inhibits platelet expression of CD40 ligand

One of the research articles in the ebola library associated raised sCD40L with survival in ebola. Maybe the immune system interaction with ebola is different than with many other viruses since that was considered a surprising finding by the authors. Could massive IV infusion of vit C interfere with any unique ebola immune response? I certainly do not know. ;)
 
Re: Ebola: Discussion

Re: Ebola: Discussion

I had already found that first article, but dismissed it (in terms of relevance to the vitamin C discussion) because it clearly says PROTEIN C. Are people really assuming,, do you think, that it's the same thing? I hope not. Thanks for the others--I'm off to read them now.
 
Re: Ebola: Discussion

Re: Ebola: Discussion

I wrote a post with a bunch of info about Vit C here a few days ago, but it was deleted without explanation.

It's unfortunate that there isn't more interest; based on my research, it's an interesting and viable treatment option -- at the very least in an adjunct / supportive role, and possibly much more.
 
Re: Ebola: Discussion

Re: Ebola: Discussion

Frankly, if we are looking for nutrient type support, Zinc is a better candidate for research and investigation into whether it has any benefit in ebola, but you would need a liquid and ionic form of it to bypass all sorts of absorption and similar problems during the early symptomatic stage of infection and especially in late stage ebola, possibly an IV.

With regard to sepsis see:-
http://www.sciencedaily.com/releases/2014/07/140715084928.htm
Zinc deficiency magnifies, prolongs lethal immune response to sepsis

Full paper.
Ming-Jie Liu, Shengying Bao, Jessica R. Napolitano, Dara L. Burris, Lianbo Yu, Susheela Tridandapani, Daren L. Knoell. Zinc Regulates the Acute Phase Response and Serum Amyloid A Production in Response to Sepsis through JAK-STAT3 Signaling. PLoS ONE, 2014; 9 (4): e94934 DOI: 10.1371/journal.pone.0094934

Not the first study to find a beneficial link between raising zinc levels and treatment of sepsis, but certainly the most recent.
 
Re: Ebola: Discussion

Re: Ebola: Discussion

Current state of play with regard to human trial research into zinc and selenium with regard to sepsis reviewed here:- indications that selenium may be beneficial, more work on zinc required. Perhaps a combination of the two might be of benefit?? Definitely worthy of further investigation IMHO, on the assumption (and its a big one) that the mechanisms of ebola infection and sepsis are broadly similar. At the right dosage levels, it would be unlikely to do any harm, and could be useful in the current crisis as it could be widely distributed, if specific ebola tests could be done quickly and showed benefits in survival and/or reductions in viral load (reduced transmissibility) during infection.

http://www.chestphysician.org/home/...-sepsis/789c75545633d0855b245750d37dc02c.html

Summary

Although selenium and zinc levels are decreased in pediatric and adult patients with sepsis, it is not clear whether correcting these alterations is of clinical benefit. Recent human trials investigating selenium supplementation are difficult to interpret in the context of sepsis as many have been conducted in patient populations that include heterogeneous forms of critical illnesses and have often included selenium in combination with other micronutrients.

The recent meta-analysis by Alhazzani and colleagues, however, provides evidence that isolated selenium supplementation may be effective in reducing mortality in patients with sepsis. The results of the recently completed clinical trial by the German Sepsis Network may provide conclusive evidence to confirm this trend. While animal studies supporting zinc supplementation in sepsis abound, human trials have investigated zinc in combination with other antioxidants, and phase 1 trials of zinc alone are only currently underway. Further large, randomized trials will be needed before zinc supplementation can be considered efficacious in reducing mortality in sepsis.
Click to expand...
 
Re: Ebola: Discussion

Re: Ebola: Discussion

Lizw said:
I had already found that first article, but dismissed it (in terms of relevance to the vitamin C discussion) because it clearly says PROTEIN C. Are people really assuming,, do you think, that it's the same thing? I hope not. Thanks for the others--I'm off to read them now.
Click to expand...

This is what I was referring to, on page 272:



That 1998 article just describes vitamin C metabolism in sepsis, without concluding administration would be good or bad. I found the interesting passage you saw about Protein C - I don't think most people would confuse the two, but they might at least get the impression that Protein C would be a good treatment for sepsis. I guess it was aggressively promoted by a drug company as a sepsis treatment for awhile but Cochrane did an unfavorable review of the product in 2011:

http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD004388.pub4/abstract;jsessionid=406C2364EFCB869EF13DFF37C416C9F7.f03t03

Vitamin C infusion is still being researched as a sepsis treatment:

Phase I safety trial of intravenous ascorbic acid in patients with severe sepsis
Journal of Translational Medicine 2014, 12:32 doi:10.1186/1479-5876-12-32

It looks good, but maybe Human Protein C did, too, in initial trials.
 
Re: Ebola: Discussion

Re: Ebola: Discussion

Sharky said:
I wrote a post with a bunch of info about Vit C here a few days ago, but it was deleted without explanation.

It's unfortunate that there isn't more interest; based on my research, it's an interesting and viable treatment option -- at the very least in an adjunct / supportive role, and possibly much more.
Click to expand...

I saw that post in the thread I started in the Alternative library and don't know where it went. :confused: Try PM'ing Sharon and see if she knows what happened.

I'm glad to see some real research is being done on using vit C in sepsis. Help is sorely needed. When it comes specifically to ebola, I'd like to see a medical expert's opinion on whether or not vit C's inhibition of the CD40 ligand would effect the body's immune response to ebola.

These are the two articles I'd ask about:

http://jid.oxfordjournals.org/content/210/4/558.full
http://www.sciencedirect.com/science/article/pii/S0891584905001012
 
Re: Ebola: Discussion

Re: Ebola: Discussion

Emily said:
That 1998 article just describes vitamin C metabolism in sepsis, without concluding administration would be good or bad.
Click to expand...

The quote about Vit C being a pro-oxidant makes it sound like that's a bad thing. One of the effects of high-dose Vit C is to increase H2O2, both in the extracellular space near cells and inside the cells, by way of the Fenton reaction, which is iron-driven.

This oxidation factor is strongly toxic for most bacteria, because they lack the catalase enzyme, which is required to metobolize H2O2. (FWIW, this same effect is true in many cancers, which also lack catalase.)

The net effect in a bacterial sepsis condition would generally be positive, in the sense of additional bacterial cell death. Whether it would be effective or curative in any particular case would depend heavily on dosing and other factors.

(my previous post was deleted because I didn't include references. I can provide them when asked, but it's time consuming, so if I need to do so for every post I make, I doubt I'll post much.)
 
Re: Ebola: Discussion of Treatments

I changed the title to "Ebola: Discussion of Treatments" so that folks would have a better idea of what is being discussed. We could either expand the topics in this thread and go back to a more general title or open other discussion threads for different topics.
 
Re: Ebola: Discussion of Treatments

Japan offers anti-influenza drug, favipiravir, for Ebola treatment

Japan said Monday it is ready to provide a Japanese-developed anti-influenza drug as a possible treatment for the rapidly expanding Ebola outbreak.

The drug, with the brand name Avigan, was developed by Fujifilm subsidiary Toyama Chemical Co. to treat new and re-emerging influenza viruses, and has not been proven to be effective against Ebola. {in people]



Favipiravir was approved by Japan's health ministry in March for use against influenza. Fujifilm is in talks with the U.S. Food and Drug Administration on clinical testing of the drug in treating Ebola, company spokesman Takao Aoki said.


Chief Cabinet Secretary Yoshihide Suga told reporters that Japan can offer favipiravir, developed by a subsidiary of Fujifilm Holdings Corp., at any time at the request of the World Health Organization.

Favipiravir inhibits viral gene replication within infected cells to prevent propagation, while other anti-viral drugs often are designed to inhibit the release of new viral particles to prevent the spread of infection, the company said.

The company has enough stock of favipiravir for more than 20,000 patients, Aoki said.

Suga, the Cabinet spokesman, said Japan is watching for a decision by WHO that would provide more details on the use of untested drugs against Ebola. In case of an emergency, Japan may respond to individual requests before any further decision by WHO, he said.

http://www.cbc.ca/news/health/ebola...s-anti-influenza-drug-for-treatment-1.2745915

~
 
Re: Ebola: Discussion of Treatments

Favipiravir

From Wikipedia, the free encyclopedia

Favipiravir also known as T-705 is an experimental anti-viral drug with activity against many RNA viruses. Like some other experimental antiviraldrugs (T-1105 and T-1106), it is a pyrazinecarboxamide derivative. Favipiravir is active against influenza viruses, West Nile virus, yellow fever virus, foot-and-mouth disease virus as well as other flaviviruses, arenaviruses, bunyaviruses and alphaviruses.<sup id="cite_ref-Furuta_1-0" class="reference">[1]</sup>

The mechanism of its actions is thought to be related to the selective inhibition of viral RNA-dependent RNA polymerase. Favipiravir does not inhibit RNA of DNA synthesis in mammalian cells and is not toxic to them.<sup id="cite_ref-Furuta_1-1" class="reference">[1]</sup>
​

<sup id="cite_ref-Furuta_1-1" class="reference">Favipiravir was approved in Japan in March 2014 for the treatment of influenza.</sup>

<sup id="cite_ref-Furuta_1-1" class="reference"></sup>
<sup id="cite_ref-Furuta_1-1" class="reference">~
</sup>
 
Re: Ebola: Discussion of Treatments


Successful treatment of advanced Ebola virus infection with T-705 (favipiravir) in a small animal model

Abstract

Outbreaks of Ebola hemorrhagic fever in sub-Saharan Africa are associated with case fatality rates of up to 90%. Currently, neither a vaccine nor an effective antiviral treatment is available for use in humans. Here, we evaluated the efficacy of the pyrazinecarboxamide derivative T-705 (favipiravir) against Zaire Ebola virus (EBOV) in vitro and in vivo. T-705 suppressed replication of Zaire EBOV in cell culture by 4 log units with an IC<sub>90</sub> of 110 μM. Mice lacking the type I interferon receptor (IFNAR<sup>−</sup><sup>/</sup><sup>−</sup>) were used as in vivo model for Zaire EBOV-induced disease. Initiation of T-705 administration at day 6 post infection induced rapid virus clearance, reduced biochemical parameters of disease severity, and prevented a lethal outcome in 100% of the animals. The findings suggest that T-705 is a candidate for treatment of Ebola hemorrhagic fever.
​
~
eta:
I think 100% survival when delaying treatment for six days after infection is really amazing

~
​
 
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