The NO-ONOO theory of oxidative stress as the cause of disease (ML Pall)

I agree with you Nathan, it seems like it should be a clue to the riddle that something might work and then become ineffective.  And then of course there's the rebound which suggests that the body got used to the "something" we were trying and it is yet another "stress" for the body to be without it again.

I'm no neuroscientist or biochemist, but I'm both fascinated and demoralized by this condition.  I was starting to feel better the month of September, thought I was really improving, and now I'm doing badly again.  I can't help  but think it is the change of seasons, lack  of sunlight, etc.  If I exert myself in any way whatsoever I get thrown into a wave of fibromyalgia and/or chronic fatigue.  I am scared to death that this is my life from now on.  I've practiced acceptance which helps, but dear lord this can't be it from here on out, can it??

My best theory at this point is that the drug changed our gene expression profile, and it may be possible to change it back, but HOW??? My autonomic nervous system feels like it has been fried, and I'm trying to do everything I can think of to enhance neuroplastic changes to become healthy again.  And I am so frustrated that NO ONE is working on this!!!

My best theory at this point is that the drug changed our gene expression profile, and it may be possible to change it back, but HOW??? My autonomic nervous system feels like it has been fried, and I'm trying to do everything I can think of to enhance neuroplastic changes to become healthy again.  And I am so frustrated that NO ONE is working on this!!!

My two personal theories as to what is going on with us are:

1.) It's some sort of positive feedback loop where various neurotransmitters/receptors have entered a pathological state where the output state feeds back to the input and drives it further into a pathological situation. That's essentially what Pall's theory is for NO/ONOO, though there are probably dozens of different physiological mechanisms that might operate in a similar fashion.

2.) Long term exposure to benzos/z-drugs have instituted epigenetic changes where some gene expression has been either down regulated or enhanced. For instance, the genes that control the production of something like GAD65 might become down regulated such that we are producing less glutamic acid decarboxylase, thus converting less glutamate to GABA. There might be dozens of different genes that might have their expression altered as a response to a constant exposure to something like a GABA PAM.

For the first one, if you could ever interrupt the loop you would think that the system would return to a non-pathological state.  For the second one, time may ultimately restore normal gene expression. Reversing epigenetic changes is also a large area of study since some epigenetic changes are thought to lead to some cancers (though most do not). The ability to wipe the epigenetic slate clean is something that is one of the holy grails of medicine at the moment.

It would be nice if someone in the medical community gave enough of a damn to look into this.

My best theory at this point is that the drug changed our gene expression profile, and it may be possible to change it back, but HOW??? My autonomic nervous system feels like it has been fried, and I'm trying to do everything I can think of to enhance neuroplastic changes to become healthy again.  And I am so frustrated that NO ONE is working on this!!!

 

My two personal theories as to what is going on with us are:

 

1.) It's some sort of positive feedback loop where various neurotransmitters/receptors have entered a pathological state where the output state feeds back to the input and drives it further into a pathological situation. That's essentially what Pall's theory is for NO/ONOO, though there are probably dozens of different physiological mechanisms that might operate in a similar fashion.

 

2.) Long term exposure to benzos/z-drugs have instituted epigenetic changes where some gene expression has been either down regulated or enhanced. For instance, the genes that control the production of something like GAD65 might become down regulated such that we are producing less glutamic acid decarboxylase, thus converting less glutamate to GABA. There might be dozens of different genes that might have their expression altered as a response to a constant exposure to something like a GABA PAM.

 

For the first one, if you could ever interrupt the loop you would think that the system would return to a non-pathological state.  For the second one, time may ultimately restore normal gene expression. Reversing epigenetic changes is also a large area of study since some epigenetic changes are thought to lead to some cancers (though most do not). The ability to wipe the epigenetic slate clean is something that is one of the holy grails of medicine at the moment.

 

It would be nice if someone in the medical community gave enough of a damn to look into this.

Nathan, Totally agree with your theories, and heck BOTH could be true.  If I were a PhD candidate I would jump on this as a thesis project!