Unfolded Protein Response and A Possible Treatment for CFS

[adreno]

Please have a look at the following screenshot :

View attachment 11063

This technology essentially extracts Topics out of Text. I would be more than happy to deploy this solution to Phoenix Rising Data with the hope of extracting Knowledge out of the Thousands of Conversations.

I was thinking something along those lines. But would the extracts give any meaning?

 

[JPV]

There is a new feature that might be a 1st step towards it.

I saw that, which is indeed a cool feature, but I was thinking more along the lines of some sort of dynamic database that can be used for crowdsourcing information by rating the effectiveness of various treatments. I know that there are a few online health databases that take this approach but it might be nice to have one just for members of this forum and our specific experiments. I'm sure that something exists out there already that would work.

 

[JPV]

This technology essentially extracts Topics out of Text. I would be more than happy to deploy this solution to Phoenix Rising Data with the hope of extracting Knowledge out of the Thousands of Conversations.

That looks great for research but I was thinking more along the lines of something where people could rate treatments and indicate side effects in a dynamic spreadsheet sort of layout.

This might be too simplistic, but I was thinking something like this...

CureTogether

 

[mariovitali]

That looks great for research but I was thinking more along the lines of something where people could rate treatments and indicate side effects in a dynamic spreadsheet sort of layout.

This might be too simplistic, but I was thinking something like this...

CureTogether

Yes that is great, there are actually so many Techniques out there which haven't been put to use as much as they should. We can find common characteristics/combinations of supplements that seem to work better, sequences of events, you name it.


Anyway, if any admin is reading these messages then i will be happy to help out.

 

[mariovitali]

I was thinking something along those lines. But would the extracts give any meaning?

Basically you can extract a ton of knowledge out of it which of course would be just hypotheses. Out of the top of my head we could see:

-Most common symptoms
-Which symptoms tend to occur together
-Which events happen after a supplement intake
-Which combinations of supplements shows better results (=lower frequency of Symptoms)

 

[adreno]

Basically you can extract a ton of knowledge out of it which of course would be just hypotheses. Out of the top of my head we could see:

-Most common symptoms
-Which symptoms tend to occur together
-Which events happen after a supplement intake
-Which combinations of supplements shows better results (=lower frequency of Symptoms)

That sounds interesting. So that is essentially machine learning algorithms.

I suggest we make a new thread about it, and get more people and ideas on board.

 

[JPV]

We need to do something. The data on the site is getting somewhat unmanageable.

 

[ZudZud]

We need to do something. The data on the site is getting somewhat unmanageable.

It can be done with a large database using associations, but the real problem will be people randomly upvoting/downvoting substances, symptoms and general spam. It needs full time watchdogs and the end result might not reveal so much. It's as much of a technical challenge as it is a human issue. However, it could be awesome.

See imdb ratings, iherb reviews, etc. for general problems with such systems.

 

[xks201]

I am presently learning computer programming and I believe this would make a good project for me. There already Is a website covering all medical conditions showing drugs reviews per conditions but this is a bit more specific. I don't know if I'd call it s machine learning but it is more specific.

 

[mariovitali]

Dear All,

After doing more research about my condition i realized that i have to check my kidney function and whether i am in the route towards Chronic Kidney Disease (CKD).

So i visited a Pathologist whom i never seen and went there prepared with several PubMed printouts and explained to him what i think is going on (Methylation Problems, Insufficient BH4 and Ultimately UPR as part of the Mechanism). He was very open and said that whatever i said made perfect sense to him but OTOH we cannot prove anything.

I have found 3 times elevated Creatinine and Urea but never had eGFR so i will be doing these next week. I am Keeping my fingers crossed...



Please make sure that you do not have BH4, GCH1 Mutations because this will impair dopamine, serotonin, epinephrine, your Nitric Oxide production and ultimately your kidneys (among other things).

Please also visit this thread

 

[nandixon]

@mariovitali, you're only heterozygous for those GCH1 SNPs, as I mentioned here:

http://forums.phoenixrising.me/inde...-bh4-relation-to-nos.19570/page-2#post-592334

More than a third of the European population is also heterozygous, if I remember correctly, so it seems you probably wouldn't want to place too much emphasis on GCH1 (at least with the data you have).

 

[mariovitali]

@nandixon

Yes that makes sense but i would like to take all things under consideration (which as you pointed out correctly, should be addressed whenever i talk about impaired BH4 Production). I could definitely see some issues with Dopamine, Epinephrine and Nitric Oxide production. My NO was very low actually. So perhaps my Methylation problems + GCH1 impairs Dopamine/Adrenaline production.

 

[Gondwanaland]

@mariovitali interesting... When I open my Promethease report my top detrimental SNPs point to urinary tract problems (kidney disease, bladder cancer). I hope I can decipher this thread and the one you linked soon. I think am having very low dopamine and adrenaline as well.

 

[mariovitali]

FYI @nandixon

More evidence on how Resveratrol could help achieve better BH4 levels :

Resveratrol reverses endothelial nitric-oxide synthase uncoupling in apolipoprotein E knockout mice.
Xia N1, Daiber A, Habermeier A, Closs EI, Thum T, Spanier G, Lu Q, Oelze M, Torzewski M, Lackner KJ, Münzel T, Förstermann U, Li H.
Author information
Abstract
A crucial cause of the decreased bioactivity of nitric oxide (NO) in cardiovascular diseases is the uncoupling of the endothelial NO synthase (eNOS) caused by the oxidative stress-mediated deficiency of the NOS cofactor tetrahydrobiopterin (BH(4)). The reversal of eNOS uncoupling might represent a novel therapeutic approach. The treatment of apolipoprotein E knockout (ApoE-KO) mice with resveratrol resulted in the up-regulation of superoxide dismutase (SOD) isoforms (SOD1-SOD3), glutathione peroxidase 1 (GPx1), and catalase and the down-regulation of NADPH oxidases NOX2 and NOX4 in the hearts of ApoE-KO mice. This was associated with reductions in superoxide, 3-nitrotyrosine, and malondialdehyde levels. In parallel, the cardiac expression of GTP cyclohydrolase 1 (GCH1), the rate-limiting enzyme in BH(4) biosynthesis, was enhanced by resveratrol. This enhancement was accompanied by an elevation in BH(4) levels. Superoxide production from ApoE-KO mice hearts was reduced by the NOS inhibitor L-N(G)-nitro-arginine methyl ester, indicating eNOS uncoupling in this pathological model. Resveratrol treatment resulted in a reversal of eNOS uncoupling. Treatment of human endothelial cells with resveratrol led to an up-regulation of SOD1, SOD2, SOD3, GPx1, catalase, and GCH1. Some of these effects were preventable with sirtinol, an inhibitor of the protein deacetylase sirtuin 1. In summary, resveratrol decreased superoxide production and enhanced the inactivation of reactive oxygen species. The resulting reduction in BH(4) oxidation, together with the enhanced biosynthesis of BH(4) by GCH1, probably was responsible for the reversal of eNOS uncoupling. This novel mechanism (reversal of eNOS uncoupling) might contribute to the protective effects of resveratrol.

and (this has been posted before)

Resveratrol Improves Vascular Function in Patients With Hypertension and Dyslipidemia by Modulating NO Metabolism

Epidemiological studies have demonstrated that the Mediterranean diet, which is rich in resveratrol, is associated with a significantly reduced risk of cardiovascular disease. However, the molecular mechanisms that underlie the beneficial effects of resveratrol on cardiovascular function remain incompletely understood. Therefore, we set out to identify the molecular target(s) mediating the protective action of resveratrol on vascular function. To this end, we performed vascular reactivity studies to evaluate the effects of resveratrol on superior thyroid artery obtained from 59 patients with hypertension and dyslipidemia. We found that resveratrol evoked vasorelaxation and reduced endothelial dysfunction through the modulation of NO metabolism via (1) an 5′ adenosine monophosphate–activated protein kinase–mediated increase in endothelial NO synthase activity; (2) a rise in tetrahydrobiopterin levels, which also increases endothelial NO synthase activity; and (3) attenuation of vascular oxidative stress, brought about by overexpression of manganese superoxide dismutase via an nuclear factor erythroid–derived 2-like 2–dependent mechanism. The effects of resveratrol on acetylcholine vasorelaxation were also tested in vessels from patients with nonhypertensive nondyslipidemia undergoing thyroid surgery. In this setting, resveratrol failed to exert any effect. Thus, our finding that resveratrol reduces endothelial dysfunction, an early pathophysiological feature and independent predictor of poor prognosis in most forms of cardiovascular disease, supports the concept that the risk of vascular events could be further reduced by adherence to a set of dietary and behavioral guidelines.

I believe that induction of BH4 levels was very important for my recovery.

 

[nandixon]

@mariovitali

I tried resveratrol 2 or 3 years ago, and didn't notice much effect. Perhaps slightly positive, but not worth the high cost. I used the best (I think) product available at the time, which was Biotivia Transmax Trans-Resveratrol (500 mg).

The problem with resveratrol is that it does a great many things - perhaps too many things, many or most of which are only achievable in vitro. So it may be difficult to tell what effect it's really having if a person experiences a benefit from taking it.

 

[mariovitali]

@mariovitali

The problem with resveratrol is that it does a great many things - perhaps too many things, many or most of which are only achievable in vitro. So it may be difficult to tell what effect it's really having if a person experiences a benefit from taking it.

Resveratrol has definitely helped me. I know this because at that time i was not getting anything else and i felt an immediate boost (but which on its own wasn't enough).

Needless to say that this condition we are having needs personalized therapy with many different parameters that have to be accounted for.

 

[adreno]

Anecdotally, fexofenadine (Allegra) can have a very mild stimulating effect in some people that might be helpfulful.

I did find it stimulating. Unfortunately, it made me quite aggressive, like dopamine rage. It also seems to be a nitric oxide killer.

 

[Sidereal]

I can't tolerate fexofenadine at all.

 

[adreno]

I can't tolerate fexofenadine at all.

What happens?

 

[Sidereal]

What happens?

Agitation.