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Article: Bad Wiring? State of the Knowledge Workshop III: Systems Biology
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The downside of this technology and the Light's work and some of the pathogen work is that it really is cutting edge stuff - and it does take awhile to become accepted; that's for sure. The best thing for us really would be to have some tried and true test show up that people with ME/CFS went bonkers on but, except for the Pacific Fatigue Lab stuff - which I thought was going to change everything overnight - we don't have. However, the exercise is working its way into research protocols - look at the Light study - and I think it will pay off in dividends over time.
We're unfortunate that low blood volume, which is consistently found in ME/CFS, is just not of interest to the medical profession. It was explained to me that it was considered a kind old research topic, and its not sexy and it doesn't involve new technology and its hard to get people to really study it. That's just bad luck. The same is true of the aerobic exercise research....there's just not that many researchers are studying that in reference to disease apparently..(Dr Snell said they weren't sure which journals to submit their studies because its so different) .so we weren't lucky there either.
To me it looks like new technologies are going to be the way out. I say that begrudgingly because in some ways research into ME/CFS is still just beginning and who knows what a concentrated search that accounts for subsets could find out using the tests we have now.
As a computer engineer who made a living solving complex problems in dynamic systems I've found that only Rick Vank was on the right track. After the NIH state of knowledge I added Dr Broderick to the list. Glad the two of them had a chat at the NIH SOK. Others like Montoya, Cheney and Myhill have interesting punctual points but I'm talking about overall problem solving approach. The fact that Dr Broderick is receiving funding is a great source of hope. I smell a biomarker is around the corner. Is Dr Broderick from Trois-Rivieres Qc? Just curious as a fellow French Canadian.
Font size: Cort, for whatever reason, the font size of this article and http://forums.phoenixrising.me/cont...s-II-Epstein-Barr-virus-and-the-Enteroviruses is very small (comments are normal size). I use (shame) IE.
I would be jumping for joy if there was a priority placed on funding what already has proven to help patients of all sorts. Glutathione related meds/supplements methylation, alpha lipoic acid, B12, all have great potential. There is plenty of empirical data that suggests these are helping relieving symptoms/disease now in a variety of patients. I would suggest a team composed of Boyd Haley, Rich Van K, and Dr Burt Berkson, and many others, to develop alternative treatments that could help many diseases from Autism to CFS to many more. The goal would be to have some affordable/workable alternative treatments in 5 years.
I hope this Gordon Broderick is means well(most likely he does), has good data to work with, is successful and doesn't have any politics too deal with. Once the results/data is complete lets hope his info ins't subject to the Big Pharma news SPIN cycle.
Get 'er done!
Now "Raj" at the CDC(big pharma, vaccine makers) is in charge of genomic research? I think it's most likely the vaccine makers are using good 'ol "Raj" and the CDC to cover their tracks. The only thing that could make it worse is if you tell me Raj is reporting to a manager from the UK....
This a no brainer and certainly is designed to obfuscate reality even more.
This a no brainer and certainly is designed to obfuscate reality even more.
Which was a revision of the Gupta model (also co authored by Vernon).
The model is interesting, but probably doesn't match reality.
The problem is that the alternative steady state in their model requires substantial upregulation of GRs to explain the alternative steady state in CFS (ie high GRs low cortisol). The authors note that their model is simplistic when it comes to the GR dynamics.
The real problem is that Jason et al. (Psych 2010) actually measured such and found that they were all downregulated rather than upregulated.
I'm sure you can guess my hypothesis for this.
Anyhow, the overall conclusion is still: more data required.
The Pacific Fatigue Lab stuff should be promoted. We have here a scientific, demonstration of an impossible to simulate unique pattern of disability. Who cares if it's not sexy supercomputers and expensive technology. It may just be a stationary bike but proof is proof!
Which was a revision of the Gupta model (also co authored by Vernon).
The model is interesting, but probably doesn't match reality.
The problem is that the alternative steady state in their model requires substantial upregulation of GRs. The authors note that their model is simplistic when it comes to the GR dynamics.
The real problem is that Jason et al. (Psych 2010) actually measured such and found that they were all downregulated rather than upregulated.
I'm sure you can guess my hypothesis for this.
Anyhow, the overall conclusion is still: more data required.
More likely a balance between GR and MR is needed. I was able to find a way to upregulate GR with a chinese herbal last January and after two weeks of nothing, I then had a marked improvement in all areas as apparently the GRs suddenly upregulated again. When I plateaued after a week and then increased the dosage, I nosedived with the larger amount and had a negative and lasting effect. The energy didn't crash too much, but other areas severely crashed, indicating to me either an excessive GR upregulation, or else some kind of backfire or negative feedback loop effect, resulting either in improper GR/MR balance or some other neuroendocrine imbalance or dysregulation, respectively, apparently in the latter case also involving neurotransmitter and related functions. So it's not an easy system to predict always, with all kinds of feedback loops, ACTH, CRH, all those hormone receptors, transmitter receptors, immune system/cytokines, etc. interacting and complicating the overall picture. I hope Broderick can get to the bottom of this disorder - he sounds very impressive and that's he on the right track.
I have no idea what's going with the font size... I know it's off - on my machine with IE the print size is large and the comments are small.
. It doesn't seem to want to be taking any corrections...???
Great summary brother!
The thing is, according to the Ben-Zvi et al. paper, Low cortisol and low GRs would indicate low stress stimulus since there is only one steady state possible. If you upregulated GRs, this would push the system into an unhealthy steady state (high GRs, low cortisol at normal stress levels, a state that the authors claim is associated with CFS.
See: http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1000273
(even if you don't understand the calculus, there are some nice graphs provided)
yes, I read that paper and talked to Dr. Ben-Zvi half a year or so ago. In my case, the CFS was brought on by downregulation of CR from corticosteroids, which was the exact condition induced in the test animals they tested the chinese herbal on. Then when they administered the active subtance from the herb (and another one), it upregulated the CRs back to normal again after 14 days. That's exactly how I experienced it, also, right around the two-week mark almost exactly. And then after a week of what I thought was a plateau, increasing the dosage apparently either upregulated CR too much, or caused some kind of imbalance or whatever happened exactly, which I still don't know yet.
Apparently - or my thinking now, at least - is that the apparent "plateau" period was actually not a plateau at all, but the system was continue to upregulate but at a more moderate level. So what I probably should have done is actually reduce or even halve the dosage, not increase it, which drove it out of the relatively narrow window of "good zone" into imbalance again. I'm trying various things to address it, and probably won't know the exact answer for a while, depending on the results of these interventions.
My point was (mostly), that a downregulated CR state is considered a normal/healthy state according to the Gupta and Ben-Zvi models. The upregulated CR state (with low cortisol) is the one that is considered unhealthy and associated with CFS according to the model.
Your experience is certainly interesting when contrasted with the model.
Not really, because glucocorticoids obviously dysregulate HPA functioning. If you take a 'normal' healthy person (or rat ;-)) and give them steroids, they will lose feedback sensitivity of the HPA and possibly adrenal insufficiency once off the steroids. If the system 'crashes' at that point and gets stuck in the lower steady state (providing their model is correct), you then have CFS (or a CFS-like fatigue condition, at least). Upregulating the receptors and feedback sensitivity by various means, either possibly through adaptogenics, or through temporary cortisol suppression as they suggest, theoretically, according to these researchers, could reset the system. My experience shows they are at least partially correct, in that I got a partial recovery from upregulating the CR again, or even totally correct and that it just requires more (or something different) than just the adaptogen to reset the system.
I don't doubt that taking corticosteroids could interfere with the sensitivity of the system.
My point was that their recovery model results in going from high GR (CFS state) to low GR (healthy state). This is the inverse of your experience.
My point was that their recovery model results in going from high GR (CFS state) to low GR (healthy state). This is the inverse of your experience.
Regarding the decreased phenylalanine metabolism or pathway Dr. Broderick said was the main or biggest problem of the 5 main differences in pathway activity in Post Infectious CFS:
The only supplement that I have ever taken that I actually feel a difference within an hour or so of taking it is "isoblast". I have wondered up until now why it helps me. I thought it was because it has 2 long chain amino acids in it ( which may be helpful, but haven't seemed to make a difference for me in other supplements) but I now believe that it is because of the phenylalanine in it.
Why not see if supplementing with phenylanaline helps?
For me, when I have done too much (which for me can mean sitting up for more than two hours on a good day) I can take a dose of Isoblast and within an hour or two the awful feeling (which I will call fatigue, but has nothing to do with tired-- just that awful (toxic?) feeling I am sure you all are familiar with, dissipates. Before Isoblast it could take days to weeks for it to finally go away.
The only supplement that I have ever taken that I actually feel a difference within an hour or so of taking it is "isoblast". I have wondered up until now why it helps me. I thought it was because it has 2 long chain amino acids in it ( which may be helpful, but haven't seemed to make a difference for me in other supplements) but I now believe that it is because of the phenylalanine in it.
Why not see if supplementing with phenylanaline helps?
For me, when I have done too much (which for me can mean sitting up for more than two hours on a good day) I can take a dose of Isoblast and within an hour or two the awful feeling (which I will call fatigue, but has nothing to do with tired-- just that awful (toxic?) feeling I am sure you all are familiar with, dissipates. Before Isoblast it could take days to weeks for it to finally go away.