Salanson dead

[Tom Kunich]

"warren" <[email protected]> wrote in message news:060620032134422214%[email protected]...
> In article
<[email protected]>,
> Tom Kunich <[email protected]> wrote:
>
> > Warren, EPO is a naturally occurring hormone that all but a few
very
> > rare and short lived people have in their bodies. The body has a
very
> > high tolerance for this stuff for several reasons. But the
important
> > thing is that it has been used in megadoses for very ill cancer patients and athletes have been
> > using it in very high doses as
well.
> > There are certain families that are missing a gene that controls
the
> > body's production of EPO and so we know that there is a very high tolerance to the stuff.
>
> They may be choosing the lesser of two evils. Wouldn't you?

There are some medications that are indeed the lesser of two evils. Happily, EPO isn't one of them.

> > There can be no allergic effect to hEPO or else you'd already have died.
>
> So the injected form of EPO behaves exactly the same as the EPO
already
> in you?

Yes. That's what the rhEPO means - (recombinant human EPO) it IS human EPO down almost to the last
molecule. There is a slight difference but nothing that is easy to detect. There are some
medications which are absolutely nothing like the one's they mimic such as the various steroids
which act as artificial testosterone, but EPO is EPO.

> Who said death was the effect we're concerned about? What about Stuart's comments about the effect
> on your body's ability to
maintain
> iron balance.

I've noted several times on this board that there can be some serious side effects from using EPO
for prolonged periods of time. The most important of them that I might suggest would be an overload
of iron on your kidney's causing kidney failure. This is caused by EPO forcing red blood cells to
generate too rapidly. These immature red blood cells die quite rapidly and they have to be scavanged
out of the blood by your kidneys. The hemoglobin contains iron. Another side effect of this is that
the iron stored in your bone marrow is pulled out which could possibly leave your body low on iron.
Taking doses of iron almost always ends up with you taking too much which then puts a further load
on your kidneys. Vicious circle and not something that people ought to be doing I think.

> Perhaps there are other effects just like when someone circumvents their body's regulation of
> testosterone or dozens of
other
> chemicals. You're familiar with the "side effects" of some drugs on
our
> physiology. Why was Pantani's natural EPO regulation so screwed up during his hospital visit? How
> is it now? Like many things in the pharmacology of sports the people who know the answers aren't
writing
> about it.

There is always the chance of some complex interaction with other hormones but not likely. I have no
doubt that extended use of EPO will cause the bodies own production to shut down and then there will
be a period of readjustment after you stop taking the stuff. But I would doubt that it would be
permanent.

In fact, athletes of young age die all the time from "natural" causes that are genetic in origin and
that is what this appears to be.

We all agree that any drugs used in athletics to increase performance are by definition bad. EPO
happens not to have substantial health risks even though it does have a very high ethical risk.

 

[Warren]

In article <[email protected]>, Tom Kunich
<[email protected]> wrote:

> "warren" <[email protected]> wrote in message
> > So the injected form of EPO behaves exactly the same as the EPO
> already
> > in you?
>
> Yes. That's what the rhEPO means - (recombinant human EPO) it IS human EPO down almost to the last
> molecule. There is a slight difference but nothing that is easy to detect. There are some
> medications which are absolutely nothing like the one's they mimic such as the various steroids
> which act as artificial testosterone, but EPO is EPO.
>
> > Who said death was the effect we're concerned about? What about Stuart's comments about the
> > effect on your body's ability to
> maintain
> > iron balance.
>
> I've noted several times on this board that there can be some serious side effects from using EPO
> for prolonged periods of time. The most important of them that I might suggest would be an
> overload of iron on your kidney's causing kidney failure. This is caused by EPO forcing red blood
> cells to generate too rapidly. These immature red blood cells die quite rapidly and they have to
> be scavanged out of the blood by your kidneys. The hemoglobin contains iron. Another side effect
> of this is that the iron stored in your bone marrow is pulled out which could possibly leave your
> body low on iron. Taking doses of iron almost always ends up with you taking too much which then
> puts a further load on your kidneys. Vicious circle and not something that people ought to be
> doing I think.

Thanks for the further info. Nick's comment that EPO was harmless didn't sound right to me and the
insight from you and Stewart about the body's reaction to it supports my hunch.

-WG

 

[Kyle Legate]

warren wrote:
>
> Thanks for the further info. Nick's comment that EPO was harmless didn't sound right to me and the
> insight from you and Stewart about the body's reaction to it supports my hunch.
>
As always, it's best to rely on the scientific evidence rather than Tom's insight. He mistakenly
ascribes a major role of the spleen (filtering out red blood cells) to the kidneys. Who knows what
else is wrong.

However, I do agree that the long term medical problems that may arise from EPO use are likely the
result of disrupted iron homeostasis, rather than a direct reaction to the EPO peptide itself.

 

[Dan]

"Tom Kunich" <[email protected]> wrote in message
news:<[email protected]>...

> There can be no allergic effect to hEPO or else you'd already have died. Therefore the only way to
> kill yourself with EPO is to use so much of it that your blood thickens up like syrup and your
> heart, being enlarged and with a deep slow stroke from athletic training, slows to the speed at
> which it stalls. This generally occurs in sleep or sometimes when you are doing something like
> meditating.
>

Not quite true, chronic use of epo has been known to be immunogenic. Also, epo is not epo...there
are alternative post-translational modifications that affect the kinetics of receptor interactions
and the half-life in the blood stream...some natural, some engineered. Here's some stuff about
immunogenicity:

Rev Clin Exp Hematol. 2002;Suppl 1:7-11. Related Articles, Links Immunogenicity of erythropoietin
and other growth factors. Indiveri F, Murdaca G.

Department of Internal Medicine, Division of Internal Medicine and Clinical Immunology, University
of Genoa, Italy.

Erythropoietin (EPO) is a 165 amino-acid sequence glycoprotein which plays an important role in
maintaining regular generation of erythrocytes, Jacobs et al. describe the cloning of the human EPO
and recombinant EPO has been introduced for the treatment of anemia in patients with renal diseases.
The extensive utilization of EPO can induce the production of neutralizing EPO antibodies, which
have been proved in patients with the non-infectious form of pure red cell aplasia (NI-PRCA), an
autoimmune disease characterized by a sudden inhibition of erythrocyte maturation and production. In
this review, the literature concerning the molecular structure and the genetic profile of EPO as
well as the relationship between neutralizing EPO antibodies and NI-PRCA have been analyzed.

And:

Cyclosporine treatment for patients with CRF who developed pure red blood cell aplasia following EPO
therapy. Chng WJ, Tan LK, Liu TC. Department of Haematology/Oncology, National University Hospital,
Singapore 119074. [email protected]

Human recombinant erythropoietin is the main treatment for anemia in renal patients. Recently, there
have been case reports of pure red blood cell aplasia (PRCA) developing in renal patients
administered erythropoietin, probably because of neutralizing antibodies detected in all these
patients. All reports were from the West, and most patients were treated with erythropoietin-alpha.
Cyclosporine is an immunosuppressive agent used to treat a spectrum of autoimmune conditions. We
report a series of Chinese renal patients who developed PRCA after treatment with
erythropoietin-alpha, suggesting that this is a problem worldwide. They were treated successfully
with cyclosporine and became transfusion independent. Copyright 2003 by the National Kidney
Foundation, Inc.

 

[Warren]

In article <[email protected]>, Dan <[email protected]> wrote:

> "Tom Kunich" <[email protected]> wrote in message
> news:<[email protected]>...
>
> > There can be no allergic effect to hEPO or else you'd already have died. Therefore the only way
> > to kill yourself with EPO is to use so much of it that your blood thickens up like syrup and
> > your heart, being enlarged and with a deep slow stroke from athletic training, slows to the
> > speed at which it stalls. This generally occurs in sleep or sometimes when you are doing
> > something like meditating.
> >
>
> Not quite true, chronic use of epo has been known to be immunogenic. Also, epo is not epo...there
> are alternative post-translational modifications that affect the kinetics of receptor interactions
> and the half-life in the blood stream...some natural, some engineered. Here's some stuff about
> immunogenicity:

Could you translate this into layman's terms please?

-WG

 

[Dan]

warren <[email protected]> wrote in message news:<090620030820342246%[email protected]>...
> Could you translate this into layman's terms please?
>
> -WG

epo is produced by sticking the gene into cells, the cells make the protein and secrete it into the
culture broth. The type of cell used makes a difference in how the epo looks, different cell types
modify the protein with chains of sugar molecules. Same protein, but different. This is how they
first detected recombinant epo, when you purify it from urine natural epo and recombinant epo behave
differently in a certain type of electric field.

The sugar molecules effect the potency of epo in a few ways. One way is that it affects how
"strongly" it interacts with the receptor. Another is that it stays in the blood longer, because old
skool epo gets filtered out by the kidneys (and into the urine) more quickly. The longer it's in the
blood, the more effective it is, the fewer injections needed. Prolonging the half life in the blood,
if you think about it, is a double edged sword for a cheater.

Anyway, there are enough cases to mention, of people developing an immune response to epo
injections. They start making antibodies to epo and stop making red cells. It could be because
"recombinant human epo" is produced in a cell line in a test tube, and not in a human, and is
therefor slightly different. We don't make antibodies to proteins encoded by our own genome unless
something goes wrong. It's called "tolerance". It's possible to break tolerance by showing our
immune system a molecule that is very similar to one of our own, but slightly different (injecting
recombinant human epo).

 

[Warren]

In article <[email protected]>, Dan <[email protected]> wrote:

> warren <[email protected]> wrote in message news:<090620030820342246%[email protected]>...
> > Could you translate this into layman's terms please?
> >
> > -WG
>
> epo is produced by sticking the gene into cells, the cells make the protein and secrete it into
> the culture broth. The type of cell used makes a difference in how the epo looks, different cell
> types modify the protein with chains of sugar molecules. Same protein, but different. This is how
> they first detected recombinant epo, when you purify it from urine natural epo and recombinant epo
> behave differently in a certain type of electric field.
>
> The sugar molecules effect the potency of epo in a few ways. One way is that it affects how
> "strongly" it interacts with the receptor. Another is that it stays in the blood longer, because
> old skool epo gets filtered out by the kidneys (and into the urine) more quickly. The longer it's
> in the blood, the more effective it is, the fewer injections needed. Prolonging the half life in
> the blood, if you think about it, is a double edged sword for a cheater.
>
> Anyway, there are enough cases to mention, of people developing an immune response to epo
> injections. They start making antibodies to epo and stop making red cells. It could be because
> "recombinant human epo" is produced in a cell line in a test tube, and not in a human, and is
> therefor slightly different. We don't make antibodies to proteins encoded by our own genome unless
> something goes wrong. It's called "tolerance". It's possible to break tolerance by showing our
> immune system a molecule that is very similar to one of our own, but slightly different (injecting
> recombinant human epo).

Thanks very much.

-WG

 

[Tom Kunich]

Thanks for the references Dan. I think that I read about this somewhere else and I understood tha it
was related to a specific product which was an engineered EPO variant designed to stay in the blood
stream longer.

"Dan" <[email protected]> wrote in message
news:[email protected]...
> "Tom Kunich" <[email protected]> wrote in message
news:<[email protected]>...
>
> > There can be no allergic effect to hEPO or else you'd already have died. Therefore the only way
> > to kill yourself with EPO is to use
so
> > much of it that your blood thickens up like syrup and your heart, being enlarged and with a
> > deep slow stroke from athletic training, slows to the speed at which it stalls. This generally
> > occurs in
sleep
> > or sometimes when you are doing something like meditating.
> >
>
> Not quite true, chronic use of epo has been known to be immunogenic. Also, epo is not epo...there
> are alternative post-translational modifications that affect the kinetics of receptor interactions
> and the half-life in the blood stream...some natural, some engineered. Here's some stuff about
> immunogenicity:
>
>
> Rev Clin Exp Hematol. 2002;Suppl 1:7-11. Related Articles, Links Immunogenicity of erythropoietin
> and other growth factors. Indiveri F, Murdaca G.
>
> Department of Internal Medicine, Division of Internal Medicine and Clinical Immunology, University
> of Genoa, Italy.
>
> Erythropoietin (EPO) is a 165 amino-acid sequence glycoprotein which plays an important role
> in maintaining regular generation of erythrocytes, Jacobs et al. describe the cloning of the
> human EPO
and
> recombinant EPO has been introduced for the treatment of anemia in patients with renal
> diseases. The extensive utilization of EPO can induce the production of neutralizing EPO
> antibodies, which have
been
> proved in patients with the non-infectious form of pure red cell aplasia (NI-PRCA), an autoimmune
> disease characterized by a sudden inhibition of erythrocyte maturation and production. In this
> review, the literature concerning the molecular structure and the genetic profile of EPO as well
> as the relationship between neutralizing EPO antibodies and NI-PRCA have been analyzed.
>
> And:
>
> Cyclosporine treatment for patients with CRF who developed pure red blood cell aplasia following
> EPO therapy. Chng WJ, Tan LK, Liu TC. Department of Haematology/Oncology, National University
> Hospital, Singapore 119074. [email protected]
>
> Human recombinant erythropoietin is the main treatment for anemia in renal patients. Recently,
> there have been case reports of pure red blood cell aplasia (PRCA) developing in renal patients
> administered erythropoietin, probably because of neutralizing antibodies detected in all these
> patients. All reports were from the West, and most patients were treated with
> erythropoietin-alpha. Cyclosporine is an immunosuppressive agent used to treat a spectrum of
> autoimmune conditions. We report a series of Chinese renal patients who
developed
> PRCA after treatment with erythropoietin-alpha, suggesting that this is a problem worldwide. They
> were treated successfully with cyclosporine and became transfusion independent. Copyright 2003 by
the
> National Kidney Foundation, Inc.

 

[Tom Kunich]

Warren, note that the symptoms of this isn't a high hematocrit or heart problems but a very low
hematocrit requiring transfusions. Using more EPO would make the problem worse.

"warren" <[email protected]> wrote in message news:090620031625226777%[email protected]...
> In article <[email protected]>, Dan <[email protected]> wrote:
>
> > warren <[email protected]> wrote in message news:<090620030820342246%[email protected]>...
> > > Could you translate this into layman's terms please?
> > >
> > > -WG
> >
> > epo is produced by sticking the gene into cells, the cells make
the
> > protein and secrete it into the culture broth. The type of cell
used
> > makes a difference in how the epo looks, different cell types
modify
> > the protein with chains of sugar molecules. Same protein, but different. This is how they first
> > detected recombinant epo, when
you
> > purify it from urine natural epo and recombinant epo behave differently in a certain type of
> > electric field.
> >
> > The sugar molecules effect the potency of epo in a few ways. One
way
> > is that it affects how "strongly" it interacts with the receptor. Another is that it stays in
> > the blood longer, because old skool
epo
> > gets filtered out by the kidneys (and into the urine) more
quickly.
> > The longer it's in the blood, the more effective it is, the fewer injections needed. Prolonging
> > the half life in the blood, if you think about it, is a double edged sword for a cheater.
> >
> > Anyway, there are enough cases to mention, of people developing an immune response to epo
> > injections. They start making antibodies
to
> > epo and stop making red cells. It could be because "recombinant
human
> > epo" is produced in a cell line in a test tube, and not in a
human,
> > and is therefor slightly different. We don't make antibodies to proteins encoded by our own
> > genome unless something goes wrong.
It's
> > called "tolerance". It's possible to break tolerance by showing
our
> > immune system a molecule that is very similar to one of our own,
but
> > slightly different (injecting recombinant human epo).
>
> Thanks very much.
>
> -WG

 

[Warren]

In article <[email protected]>, Tom Kunich
<[email protected]> wrote:

> Warren, note that the symptoms of this isn't a high hematocrit or heart problems but a very low
> hematocrit requiring transfusions. Using more EPO would make the problem worse.

That's pretty much what I said my hunch was from the start. You screw around with the body's
regulation of something by taking EPO, Testosterone, etc. and you'll end up in trouble over the
long-term or at least until your mechanisms can regain your natural equilibrium.

-WG

 

[Tom Kunich]

"warren" <[email protected]> wrote in message news:090620031923399507%[email protected]...
> In article
<[email protected]>,
> Tom Kunich <[email protected]> wrote:
>
> > Warren, note that the symptoms of this isn't a high hematocrit or heart problems but a very low
> > hematocrit requiring transfusions.
Using
> > more EPO would make the problem worse.
>
> That's pretty much what I said my hunch was from the start. You
screw
> around with the body's regulation of something by taking EPO, Testosterone, etc. and you'll end up
> in trouble over the long-term
or
> at least until your mechanisms can regain your natural equilibrium.

This is probably very rare and it would jump right off of the page of a coroner's report - it would
be a hematocrit of something horrible like under 20.