Ronald W. Davis, PhD's presentation at the IIMEC13

Looking through a different perspective what Dr Davis discussed :




Trypanosomes and Liver Disease :

Trypanosoma cruzi, the etiological agent of Chagas' disease, causes an intense inflammatory response in several tissues, including the liver. Since this organ is central to metabolism, its infection may be reflected in the outcome of the disease. 15-deoxy-Δ12,14 prostaglandin J2(15dPGJ2), a natural agonist of peroxisome-proliferator activated receptor (PPAR) γ, has been shown to exert anti-inflammatory effects in the heart upon T. cruzi infection. However, its role in the restoration of liver function and reduction of liver inflammation has not been studied yet.


https://www.ncbi.nlm.nih.gov/pubmed/27693222


Low Selenium :

Selenium in chronic liver disease.
Thuluvath PJ1, Triger DR.
Author information

Abstract
In order to assess the role of selenium (Se) in chronic liver disease, we have measured serum, urinary and hepatic selenium in a range of liver diseases and correlated them with nutritional status and conventional liver biochemistry. Serum Se levels (microgram/l +/- S.D.) were significantly lower in both alcoholic (63.6 +/- 18.2, p less than 0.0001) and non-alcoholic liver disease (NALD) (60.6 +/- 13.6, p less than 0.0001) compared to healthy controls (87.8 +/- 21.2) and non-malignant 'disease controls' (80.3 +/- 19.1). Hepatic Se levels (microgram/g of dry weight) were also reduced in both ALD (0.568 +/- 0.647, p less than 0.005) and NALD (0.863 +/- 0.308, p less than 0.005) compared to controls (1.227 +/- 0.296), 24-h urinary Se excretion (microgram) in ALD (24.6 +/- 10.7) and NALD (29.0 +/- 14.3) was similar to controls (30.3 +/- 8.7). Serum Se showed a highly significant positive correlation with albumin (p less than 0.001) in both ALD and NALD. Serum levels were also significantly correlated with anthropometric measurements. Dietary assessment of patients with primary biliary cirrhosis and low serum Se levels did not show a reduced dietary intake. Our data show that Se levels are low in liver disease irrespective of aetiology and suggest that these low levels are more likely to be related to overall nutritional status than to dietary intake.

Link : https://www.ncbi.nlm.nih.gov/pubmed/1500682

Status of Trace Minerals in Liver Disease :


Essential trace minerals such as zinc (Zn), selenium (Se), and copper (Cu) not only act as antioxidants but also play vital roles in multiple metabolic processes in the liver [10]. Disturbances in the homeostasis of these minerals can cause oxidative stress and inflammatory changes, thus enhancing HCV replication, exacerbating hepatic fibrosis and IR, and reducing the effectiveness of anti-viral therapy in chronic HCV-infected patients [6,7,9]. Liver diseases may alter the regulation of trace mineral metabolism and homeostasis. However, Zn supplementation prevents increases in transaminases, reduces liver fibrosis and triglyceride levels, and improves the long-term outcome of these patients [7,11,12]. Blood Se concentrations decrease in proportion to the severity of HCV-induced hepatic injury. Se supplementation may be effective therapy for reducing IR and hepatic fibrosis in patients with chronic HCV infection [9,13]. Therefore, the maintenance of essential metal homeostasis is a crucial therapeutic target for hepatitis C [6]. Disturbances in plasma concentrations of these minerals can accelerate deterioration of hepatitis C and prevent the achievement of SVR.

Link : http://www.medsci.org/v10p0730.htm


From my presentation in EUROMENE, Slide 10 mentioned how Zinc supplementation has helped my Symptoms :


Screen Shot 2018-09-17 at 22.41.33.png


Slide 39, the consequences of Viral Infection on Liver function : Reading the annotated text we see Alterations in Bile Secretion, Gluconeogenesis, Glycolysis, Detoxification and Balance of Nutrients :



Screen Shot 2018-09-17 at 22.49.16.png


I Hypothesise that ME/CFS patients do not have a Viral Infection. A Liver Injury (from Viral Infection, some medications and even prolonged stress) along with an unfortunate combination of problems in Phagocytosis, ER Stress, Vitamin K Metabolism and Inflammatory Processes results in a vicious cycle of Inflammation, Oxidative Stress and Autoimmunity with several negative implications.
 
It's interesting that both Ron Davis and Nancy Klimas think that ME is a "metabolic trap" that should turn out to be fairly easy to "escape" once it's understood. Are they working together on this idea, or have they just come to this conclusion independently?

Along the same lines, has anyone heard anything about Dr. Klimas' current GWI study? A similar intervention in a few ME patients was supposed to have begun in "early 2018," but that's the last I heard of it.
 
It's interesting that both Ron Davis and Nancy Klimas think that ME is a "metabolic trap" that should turn out to be fairly easy to "escape" once it's understood.
I'm not a fan of this view. I think its an over simplistic framework that many things could (will) be shoehorned into but is basically a mold that is an abstraction. Not sure if that is making much sense.
 
I'm not a fan of this view. I think its an over simplistic framework that many things could (will) be shoehorned into but is basically a mold that is an abstraction. Not sure if that is making much sense.

I Second that.

Unfortunately i do not agree with Dr Davis's comment that in a few days with one pill everything will be over (if this theory is right)
 
I Second that.

Unfortunately i do not agree with Dr Davis's comment that in a few days with one pill everything will be over (if this theory is right)

He may be right, or it may be a symptomatic treatment or it may be a "reset" pill whenever a patient relapses (since most patients were not born with ME/CFS and lived many years before something triggered it).

I don't agree with the theory you posted above and in the other thread, i suspect ME is an immune mediated disease, something sets off the cascade and it ratchets down energy production. The long term ratcheting down is caused by PEM/anaerobic activity or autoimmunity for some or some other method such as everyday immune activities (our immune systems are working every second of every day to keep us alive). The reason for ratcheting down is likely a bit different for each patient, if its B cell autoimmune then Rituximab may be the proper treatment, if its viral load then antivirals may be the right treatment for that patient. But whats causing it may be a few fold so each type would require its proper treatment yet i suspect they are all leading to Rome, a few different causes making the immune system to go down the same maladaptive path. This would also explain why various researchers including Dr Davis have found the same dysfunctions in all patients while some respond to Rituximab (something being investigated by Dr Scheibenbogen), because the cause may be a few different ones but the cascade beyond trigger is the same with the caveat that some might have a trigger that has long gone while some have a trigger that remains in the body which can be treated.

Hence its likely to be some form of protective mechanism gone wrong, our immune system does lower our activity level when fighting colds and other large infections, but ME is likely a constant state that keeps getting stronger and making us worse.

But i do agree that its probably treatable if we could understand the disease mechanism and hit it with some drug, some patients are relapsing/remitting and some experience dramatic improvements spontaneously. Why is the million dollar question.
 
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So far as I can see there is little point in non-experts like me deciding to 'agree' or 'disagree' with scientific hypotheses presented by people investigating ME.

I don't even begin to understand the complexities of the physiology and biochemistry going on in our bodies, so deciding which hypothesis I prefer is no better than deciding what colour I like best.

All I can do is wait for there to be sufficient scientific evidence to support one hypothesis or disprove another, and enjoy trying to get my head around the basics of the research that is published because I find it fascinating.

I tend to be suspicious when people step outside their particular specialism and on the basis of some reading about other people's research or machine learning technique, or listening to an expert they like, they declare they know what is going on. The more convinced they are that they are right, the less I trust their claims.
 
But i do agree that its probably treatable if we could understand the disease mechanism and hit it with some drug, some patients are relapsing/remitting and some experience dramatic improvements spontaneously. Why is the million dollar question.
And some are probably like me, with dramatic improvements early on, for half a day or more, then a change in diet brings about considerable improvement for up to one or two years, then relapse again. Then a different (blood pressure) drug brings about considerable improvement but some reduction in energy for one or two years, then new problems arise...

What if the 'new discovery' only works for a year or two?

(At least with all the work that's going on they might know why.)
 
So far as I can see there is little point in non-experts like me deciding to 'agree' or 'disagree' with scientific hypotheses presented by people investigating ME.

I don't even begin to understand the complexities of the physiology and biochemistry going on in our bodies, so deciding which hypothesis I prefer is no better than deciding what colour I like best.

All I can do is wait for there to be sufficient scientific evidence to support one hypothesis or disprove another, and enjoy trying to get my head around the basics of the research that is published because I find it fascinating.

I tend to be suspicious when people step outside their particular specialism and on the basis of some reading about other people's research or machine learning technique, or listening to an expert they like, they declare they know what is going on. The more convinced they are that they are right, the less I trust their claims.

Trish,

I do understand your point of view. Unfortunately i am not good with words -i can definitely say this- and what i tried was putting my point of view that i find the metabolic trap hypothesis simplistic. I do not have the capacity and did not in any way suggested that there is no point in looking at all of this. Dr Davis presented several findings and as i mentioned in my post i looked through a different perspective his talk.

I hope this clears any misunderstanding.
 
Trish,

I do understand your point of view. Unfortunately i am not good with words -i can definitely say this- and what i tried was putting my point of view that i find the metabolic trap hypothesis simplistic. I do not have the capacity and did not in any way suggested that there is no point in looking at all of this. Dr Davis presented several findings and as i mentioned in my post i looked through a different perspective his talk.

I hope this clears any misunderstanding.

No misunderstanding. I wasn't responding directly to your comment, more to the general impression that several people were expressing preference for one theory or another. I was just expressing my way of dealing with being presented with lots of different theories, which is basically an attitude of wait and see.
 
So far as I can see there is little point in non-experts like me deciding to 'agree' or 'disagree' with scientific hypotheses presented by people investigating ME.
To a point i agree, my theory was a response to another theory which was not part of the original thread intent or content.


And some are probably like me, with dramatic improvements early on, for half a day or more, then a change in diet brings about considerable improvement for up to one or two years, then relapse again. Then a different (blood pressure) drug brings about considerable improvement but some reduction in energy for one or two years, then new problems arise...

What if the 'new discovery' only works for a year or two?

(At least with all the work that's going on they might know why.)
This is why i hate accidental unexplained discoveries. When you don't know whats going on the results are unpredictable which drives me bonkers.
That said i love accidental but explained discoveries
 
Hence its likely to be some form of protective mechanism gone wrong, our immune system does lower our activity level when fighting colds and other large infections, but ME is likely a constant state that keeps getting stronger and making us worse.

This goes along with Dr. Paul Cheney's theory- 'protective mechanism'.
 
Until any scientific expert proves otherwise, I am going to continue to believe that ME is a particular condition brought down upon people who thought they could think through things just to prove that they can't. Indirectly it supports the hypothesis that we are all still in the Matrix.
 
Until any scientific expert proves otherwise, I am going to continue to believe that ME is a particular condition brought down upon people who thought they could think through things just to prove that they can't. Indirectly it supports the hypothesis that we are all still in the Matrix.

But if we were living in the Matrix, would the Matrix allow the movie "The Matrix" to be made, thus making people suspicious that they might be in the Matrix? Would I even be allowed to write this post to discuss... wait a minute - there's a knock at the door.
 
44:48 mins Metabolic Trap:
What they think is happening (best guess at the moment), is because of the genetics and inflammation that gets started is that you can get yourself
in a situation where your pathways which are normally supposed to work, get altered because of the mutations and metabolites and
enyzamatic process gets trapped into a non functional state. When he says trapped, there is no easy way out.
So what this would predict, is that something would trigger it (an infection), it would change your metabolism to the point where it
gets trapped. That would happen almost instantaneous, you would go to sleep and wake up with the disease.
and nothing you do will get you out of it, there will be no drugs to get you out of it. The good news is that by understanding what
it is if this is all true, it will probably be very easy to fix. But it won't be something anybody's tried. They'll have to manipulate the
metabolism, but, it should be very inexpensive to do it and should take you a few days to get out of it.":woot:
 
Sleeping sickness only manifests once the trypanosomes cross the blood-brain barrier. Once they do so, the trypanosomes apparently induce sleeping sickness as a consequence of their manufacture of the molecule tryptophol.

There's something else in the body that can produce tryptophol, though - the yeast Candida albicans. The overgrowth of C. albicans in the gut has been proposed as a cause of CFS since the mid-1980's, but the proposed mechanism has been via the yeast's production of acetaldehyde - a molecule also produced in the liver during the breakdown of alcohol. Acetaldehyde is thought to mediate hangover symptoms, which led some to believe that it was connected to CFS symptoms like light and sound sensitivity.

I don't know if excessive tryptophol produced by C. albicans overgrowth in the gut could make its way from the gut to the brain and cross the blood-brain barrier, but I have often wondered if ME/CFS might not be a form of "poisoning" via some seemingly normal process run amok.
 
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