Re: Glutathione depletion and idiopathic cardiomyopathy in CFS

[Guest guest]

Those are indeed some nice tallies with your ideas - you must be

having a field day with this stuff

I think Cheney might be interested in hearing your take. I just

reviewed his stuff and I understand it better now than I did earlier

today. While he emphasizes that this is merely what he'd wager on, in

the idea he's putting forward, the heavy metal accumulation in the

heart IS the lasting damage left by the cardiotropic pathogen - and I

think he's saying that there isnt necessarily heart tissue damage in

the " normal " sense. That's what I didnt grasp earlier today.

And I think he's saying that this accumulation of heavy metal in the

heart is what makes the heart super sensitive to NO, because the heavy

metal can interfere with SOD, thus causing the increase in superoxide,

which is the rate-limiting contributer to the formation of

peroxynitrate in the presence of NO.

So its cardiotropic infection (maybe) >> astronomical heavy metal

concentrations in the heart, in the absence of effective detox >>

inability to avert peroxynitrate production - ?

But from here I get confused. Is he hinting that peroxynitrate then

damages heart tissue progressively by oxidative cytotoxicity? Also,

its unclear where the high expression of NO is coming from. Cheney

hints at iNOS as the probable source, and hints at " immune activation "

due to antigen as the cause of iNOS expression - which presumably

means theres a chronic infection (this one not necessarily very

cardiotropic).

And he doesnt get into the chronic infection part really at all, so

maybe hes at a bit of a loss there and would be interested in trying

out in some of your ideas, Rich, at this point way up at the

headwaters of the causal stream.

Personally, I had a broken mercury thermometer in my bag for probably

a full week when I was living in the woods. I had only a lawn tarp to

keep the very thick mosquitos off me - so every night for a week I

slept basically *sealed* into a very small space with this mercury. I

then moved into a house and promptly spilled the same mercury from my

bag onto the carpet (which is how I first discovered it). This was 3

years before I even started to slowly get CFIDS and I had no medical

or biological knowledge but I knew this was bad. I ran a fan in the

room the whole rest of the summer with another window open for intake,

and I did a 24h urine specimin - it was " negative " for excessive Hg,

but we all know that some medical determinations are alot better

founded than others...

Anyway, I still dont see how all this gets a person swollen glands (I

know no theory is nearly perfect so far, eg the most advanced and

speculative understanding of lyme disease leaves some VERY odd ends,

but I'm just sayin').

And personally I am definitely going to read the paper Cheney cited on

Hg in the heart, but I still think one might find serious vasculitis

if some of these hearts were to be cut up, and that might be the

bottom of all this. Which leads me to wonder, what did Cheney do with

his old heart? Seems a pity to toss it out - one should do some

histology on it, and a heavy metal assay! Speaking of which, if anyone

on this list dies, please have yourself mailed to my house (except

Rich, who doesnt have A-CID).

<richvank@a...> wrote:

>

> Hi, all.

>

> I want to point out that glutathione depletion looks like a very

> good candidate to explain the cardiomyopathy that Dr. Cheney

> discussed in the recent write-up by Carol Sieverling:

>

> http://www.virtualhometown.com/dfwcfids/medical/cheney/heart04.htm

>

> Dr. Cheney noted under " Etiology (Cause) " that " The short version is

> that cardiac muscles have lost power because their mitochondria are

> dysfunctional. They're not functioning well because of a redox-

> state problem. But, what causes the redox-state problem? I don't

> know... "

>

> I would just point out that the redox potential in cells is normally

> controlled by glutathione. A depletion of glutathione in the heart

> muscle cells would very definitely lead to a " redox-state " problem

> and dysfunction of the mitochondria.

>

> Dr. Cheney also discussed viruses, heavy metals and toxins as

> possible causes of the cardiomyopathy. I would just point out that

> some of the other well-known roles of glutathione in the body are to

> suppress the activation of viruses and to remove heavy metals and

> other toxins from the body.

>

> Dr. Cheney further discussed the increase in concentration of

> peroxynitrite, as is the basis of Prof. Pall's theory, as a

> causative mechanism. He noted that the rise in superoxide is what

> causes the increase in peroxynitrite concentration. I would point

> out that glutathione depletion can be responsible for the rise in

> superoxide concentration as well, since it will promote a rise in

> the concentration of hydrogen peroxide, and this in turn will

> exert " product inhibition " on the superoxide dismutase reaction.

> This backlog will cause superoxide to rise.

>

> In summary, I think that all the mechanisms that Dr. Cheney cited as

> possibly being responsible for cardiomyopathy in CFS can in turn be

> caused by glutathione depletion. I think this offers the

> possibility of putting together a comprehensive hypothesis for the

> pathogenesis of CFS. I suggest that genetic predisposition,

> combined with the mechanisms I presented in my recent AACFS poster

> paper, may very well serve as the " front end " of a comprehensive

> hypothesis for the etiology and pathogenesis of CFS, which can be

> combined with Dr. Cheney's new thinking about the cardiomyopathy to

> explain a major part of what goes on in CFS.

>

> I would also note that this approach can also explain the milder

> cases of CFS, in which cardiomyopathy is not observed. The reason

> for this would be that it is known that the heart has a higher

> concentration of the rate-limiting enzyme needed for synthesizing

> glutathione than do most of the other organs of the body.

> Therefore, in the early stages of CFS, the heart is able to maintain

> its concentration of glutathione sufficiently high to avoid the

> mitochondrial dysfunction, which may result from a redox shift,

> toxin buildup, or reactivation of endogenous viruses.

>

> My glutathione depletion paper can be found at any of the following

> three websites:

>

> http://www.personalconsult.com/articles/glutathioneandchronicfatigue.

> html

>

> http://www.cfsresearch.org/cfs/research/treatment/26nf.htm

>

> or

>

> http://phoenix-cfs.org/GluAACFS04.htm

>

>

> Rich

[Guest guest]

In addition to the cardiac vasculitis angle - in one lab mammal

spirochetes (I think it was a Borrelia sp) have been found in the

cytoplasm cardiac myocytes (muscle cells) themselves, surrounded by an

area cleared of muscle fibers. I dono if this is typical of

heart-invading pathogens, of which there are alot; I dono anything

about them generally.

i wrote:

> but I still think one might find serious vasculitis

> if some of these hearts were to be cut up, and that might be the

> bottom of all this.

[Guest guest]

Hi, .

> >

> > Hi, all.

> >

> > I want to point out that glutathione depletion looks like a very

> > good candidate to explain the cardiomyopathy that Dr. Cheney

> > discussed in the recent write-up by Carol Sieverling:

> >

> >

http://www.virtualhometown.com/dfwcfids/medical/cheney/heart04.htm

> >

> > Dr. Cheney noted under " Etiology (Cause) " that " The short

version is

> > that cardiac muscles have lost power because their mitochondria

are

> > dysfunctional. They're not functioning well because of a redox-

> > state problem. But, what causes the redox-state problem? I don't

> > know... "

> >

> > I would just point out that the redox potential in cells is

normally

> > controlled by glutathione. A depletion of glutathione in the

heart

> > muscle cells would very definitely lead to a " redox-state "

problem

> > and dysfunction of the mitochondria.

> >

> > Dr. Cheney also discussed viruses, heavy metals and toxins as

> > possible causes of the cardiomyopathy. I would just point out

that

> > some of the other well-known roles of glutathione in the body

are to

> > suppress the activation of viruses and to remove heavy metals and

> > other toxins from the body.

> >

> > Dr. Cheney further discussed the increase in concentration of

> > peroxynitrite, as is the basis of Prof. Pall's theory, as

a

> > causative mechanism. He noted that the rise in superoxide is what

> > causes the increase in peroxynitrite concentration. I would point

> > out that glutathione depletion can be responsible for the rise in

> > superoxide concentration as well, since it will promote a rise in

> > the concentration of hydrogen peroxide, and this in turn will

> > exert " product inhibition " on the superoxide dismutase reaction.

> > This backlog will cause superoxide to rise.

> >

> > In summary, I think that all the mechanisms that Dr. Cheney

cited as

> > possibly being responsible for cardiomyopathy in CFS can in turn

be

> > caused by glutathione depletion. I think this offers the

> > possibility of putting together a comprehensive hypothesis for

the

> > pathogenesis of CFS. I suggest that genetic predisposition,

> > combined with the mechanisms I presented in my recent AACFS

poster

> > paper, may very well serve as the " front end " of a comprehensive

> > hypothesis for the etiology and pathogenesis of CFS, which can be

> > combined with Dr. Cheney's new thinking about the cardiomyopathy

to

> > explain a major part of what goes on in CFS.

> >

> > I would also note that this approach can also explain the milder

> > cases of CFS, in which cardiomyopathy is not observed. The reason

> > for this would be that it is known that the heart has a higher

> > concentration of the rate-limiting enzyme needed for synthesizing

> > glutathione than do most of the other organs of the body.

> > Therefore, in the early stages of CFS, the heart is able to

maintain

> > its concentration of glutathione sufficiently high to avoid the

> > mitochondrial dysfunction, which may result from a redox shift,

> > toxin buildup, or reactivation of endogenous viruses.

> >

> > My glutathione depletion paper can be found at any of the

following

> > three websites:

> >

> >

http://www.personalconsult.com/articles/glutathioneandchronicfatigue.

> > html

> >

> > http://www.cfsresearch.org/cfs/research/treatment/26nf.htm

> >

> > or

> >

> > http://phoenix-cfs.org/GluAACFS04.htm

> >

> >

> > Rich