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Road Cycling
Published
3 June 2003
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11 June 2003
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Alexander Lackn
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  1. "warren" <[email hidden]> wrote in message "]news:[email hidden]...

    Quoted message said:

    In article


    <[email hidden]>,

    Quoted message said:
    Tom Kunich said:

    Warren, EPO is a naturally occurring hormone that all but a few


    very

    Quoted message said:
    Quoted message said:

    rare and short lived people have in their bodies. The body has a


    very

    Quoted message said:
    Quoted message said:

    high tolerance for this stuff for several reasons. But the


    important

    Quoted message said:
    Quoted message said:

    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.

    Quoted message said:
    Quoted message said:

    There are certain families that are missing a gene that controls


    the

    Quoted message said:
    Quoted message said:

    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.

    Quoted message said:
    Quoted message said:

    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

    Quoted message said:

    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.

    Quoted message said:

    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

    Quoted message said:

    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.

    Quoted message said:

    Perhaps there are other effects just like when someone circumvents their body's regulation of
    testosterone or dozens of


    other

    Quoted message said:

    chemicals. You're familiar with the "side effects" of some drugs on


    our

    Quoted message said:

    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

    Quoted message said:

    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.

  2. In article <[email hidden]>, Tom Kunich

    Quoted message said:

    "warren" <[email hidden]> wrote in message

    Quoted message said:

    So the injected form of EPO behaves exactly the same as the EPO


    already

    Quoted message said:

    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.

    Quoted message said:

    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

    Quoted message said:

    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

  3. warren said:


    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.

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

    Quoted message said:

    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 hidden]

    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.

  5. In article said:

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

    Quoted message said:

    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

  6. warren <[email hidden]> wrote in message news:<[email hidden]>...

    Quoted message said:

    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).

  7. In article said:

    warren <[email hidden]> wrote in message news:<[email hidden]>...

    Quoted message said:

    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

  8. 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 hidden]> wrote in message
    "]news:[email hidden]...

    Quoted message said:

    "Tom Kunich" <[email hidden]> wrote in message


    news:<[email hidden]>...

    Quoted message said:


    Quoted message said:

    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

    Quoted message said:
    Quoted message said:

    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

    Quoted message said:
    Quoted message said:

    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

    Quoted message said:

    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

    Quoted message said:

    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 hidden]

    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

    Quoted message said:

    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

    Quoted message said:

    National Kidney Foundation, Inc.

  9. 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 hidden]> wrote in message "]news:[email hidden]...

    Quoted message said:
    In article said:

    warren <[email hidden]> wrote in message news:<[email hidden]>...

    Quoted message said:

    Could you translate this into layman's terms please?

    -WG

    epo is produced by sticking the gene into cells, the cells make


    the

    Quoted message said:
    Quoted message said:

    protein and secrete it into the culture broth. The type of cell


    used

    Quoted message said:
    Quoted message said:

    makes a difference in how the epo looks, different cell types


    modify

    Quoted message said:
    Quoted message said:

    the protein with chains of sugar molecules. Same protein, but different. This is how they first
    detected recombinant epo, when


    you

    Quoted message said:
    Quoted message said:

    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

    Quoted message said:
    Quoted message said:

    is that it affects how "strongly" it interacts with the receptor. Another is that it stays in
    the blood longer, because old skool


    epo

    Quoted message said:
    Quoted message said:

    gets filtered out by the kidneys (and into the urine) more


    quickly.

    Quoted message said:
    Quoted message said:

    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

    Quoted message said:
    Quoted message said:

    epo and stop making red cells. It could be because "recombinant


    human

    Quoted message said:
    Quoted message said:

    epo" is produced in a cell line in a test tube, and not in a


    human,

    Quoted message said:
    Quoted message said:

    and is therefor slightly different. We don't make antibodies to proteins encoded by our own
    genome unless something goes wrong.


    It's

    Quoted message said:
    Quoted message said:

    called "tolerance". It's possible to break tolerance by showing


    our

    Quoted message said:
    Quoted message said:

    immune system a molecule that is very similar to one of our own,


    but

    Quoted message said:
    Quoted message said:

    slightly different (injecting recombinant human epo).

    Thanks very much.

    -WG

  10. In article <[email hidden]>, Tom Kunich

    Quoted message said:

    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

  11. "warren" <[email hidden]> wrote in message "]news:[email hidden]...

    Quoted message said:

    In article


    <[email hidden]>,

    Quoted message said:
    Tom Kunich said:

    Warren, note that the symptoms of this isn't a high hematocrit or heart problems but a very low
    hematocrit requiring transfusions.


    Using

    Quoted message said:
    Quoted message said:

    more EPO would make the problem worse.

    That's pretty much what I said my hunch was from the start. You


    screw

    Quoted message said:

    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

    Quoted message said:

    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.

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