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Thoughtforfood said:
Okay, so selling food to Ethiopian organized crime...

Except that they would just take it and hack me to pieces with a machete...LOOK it would be easy OKAY!!!
 
Cobber said:
Thanks for your input Krebs cycle. One question... did the authors of the '99 study go back and analyse the suspicious samples using the newer EPO test? If they did indeed test positive then the original regression could be modified to account for this and be a lot more sensitive.

Also, it was Cobblestones post above. talking about the rediculously low retic %ages, not mine.
Yes I am fairly certain that those 2 suspicious samples have all but been wiped from influencing the present statistical model that the bio-passport is based on due to the additional pool of data from newer studies such as below. Another reason the thresholds are high is due to the legalities of an acceptable level of probability of obtaining a false positive. Not sure about the 3rd generation models, but in 2000 I do not believe the IOC and WADA were going to accept anything less than a 1 in 10000 chance.

Sharpe K, Ashenden MJ, Schumacher YO.
Haematologica. 2006 Mar;91(3):356-63. A third generation approach to detect erythropoietin abuse in athletes.
 
blackcat said:
Krebs the different epo-similars give a different reading on the assay correct. Different bands?

Why cannot riders reduce their micro-dose, to part micro-dose, using two or three different epo-similars?

traditional, aicar, hematide, dynepo, cera (more careful on that with half life) aranesp (similar think its half life is longer).

Could you theoretically have a medicine cabinet full of epo-similars, and then just divide your microdose between each version. That is never gonna show up, as long as you are careful with those that have a long half life.
yeah not sure about the intricacies of the assays but in regards to another query about autologous transfusions is that the suppressed erythropeitic response resulting in low retics can easily be counteracted via the use of altitude and/or EPO microdosing.

THE biggest problem that I can see with all of the studies that are conducted in this field is that many of them are based on a single manipulation technique which is part of an a priori experiemental approach. For example, the studies that have examined autologous infusions may not conducted simultaneous plasma volume expansion, so they could erroneously conclude that indirect blood markers are sufficient to detect the manipulation. However, I suspect that the doping programs are highly reactive in their approach. They conduct monitoring themselves and apply the appropriate techniques to stay within the thresholds. At present, as far as I can see, any method that contains either hct or [Hb] (ie: is conentration dependent) is a) subject to easy manipulation, and b) difficult to obtain reliable measures in the first place. The tests need to move away from concentration dependent variables and start looking at the criterion variable in all this = total Hb mass. The variability of tHbmass is much lower than hct or [hb] for example, so the threshold can be much tighter.

Bring on CO rebreathing WADA/IOC/UCI/IAAF !!
 
Mar 18, 2009
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Krebs cycle said:
yeah not sure about the intricacies of the assays but in regards to another query about autologous transfusions is that the suppressed erythropeitic response resulting in low retics can easily be counteracted via the use of altitude and/or EPO microdosing.

THE biggest problem that I can see with all of the studies that are conducted in this field is that many of them are based on a single manipulation technique which is part of an a priori experiemental approach. For example, the studies that have examined autologous infusions may not conducted simultaneous plasma volume expansion, so they could erroneously conclude that indirect blood markers are sufficient to detect the manipulation. However, I suspect that the doping programs are highly reactive in their approach. They conduct monitoring themselves and apply the appropriate techniques to stay within the thresholds. At present, as far as I can see, any method that contains either hct or [Hb] (ie: is conentration dependent) is a) subject to easy manipulation, and b) difficult to obtain reliable measures in the first place. The tests need to move away from concentration dependent variables and start looking at the criterion variable in all this = total Hb mass. The variability of tHbmass is much lower than hct or [hb] for example, so the threshold can be much tighter.

Bring on CO rebreathing WADA/IOC/UCI/IAAF !!

+1. Hematocrit and [Hb] are dependent on plasma volume. Reticulocytes % and hemoglobin mass (the latter tested with carbon monoxide rebreathing) are not dependent on plasma volume. While reticulocyte % can be manipulated with EPO or altitude training if taking autologous blood transfusions as mentioned by Krebs Cycle, hemoglobin mass is much more difficult to manipulate.
 
Jul 28, 2009
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Cobber said:
Oooh... can I get in on that too? Maybe I could develop a a procedure to produce EPO in culture that adds the same sugars as the body does? :D
Well Dyn-EPO is supposed to have a human-like carbohydrate stucture but is still biochemically distinct from endogenous EPO so even EPO produced in human cell types in various studies can still be distinguished.
 
Jul 25, 2009
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Krebs cycle said:
...the suppressed erythropeitic response resulting in low retics...

Is it right that high hemoglobin (conc. or mass) generally suppresses erythropoeitic response and therefore retic count? So, if an athlete had elevated heamoglobin levels due to altitude training, does this mean that retic count will drop when they return to sea level? The reason I'm interested it that, if reticulocytes survive for roughly a day, and other RBCs survive for roughly a hundred days, this raises the possibility of low retic / elevated Hb over some weeks. In this case the off-score sanction threshold for individual samples would need to be generous but altitude training vs homologous doping could theoretically be determined form whereabouts/altitude records.

The bio-passport may already do this; I'm not trying to critique it, just understand it a bit better. Comments would be appreciated; google has not been my friend in this instance.
 
I Watch Cycling In July said:
Is it right that high hemoglobin (conc. or mass) generally suppresses erythropoeitic response and therefore retic count? So, if an athlete had elevated heamoglobin levels due to altitude training, does this mean that retic count will drop when they return to sea level? The reason I'm interested it that, if reticulocytes survive for roughly a day, and other RBCs survive for roughly a hundred days, this raises the possibility of low retic / elevated Hb over some weeks. In this case the off-score sanction threshold for individual samples would need to be generous but altitude training vs homologous doping could theoretically be determined form whereabouts/altitude records.

The bio-passport may already do this; I'm not trying to critique it, just understand it a bit better. Comments would be appreciated; google has not been my friend in this instance.
With altitude what tends to happen is that %retics increase over the first 3-4 days and then they regress back to normal. [Hb] goes up after about 3 days due to hemoconcentration and then, if you get the stimulous right, tHbmass will gradually start to rise after 10-14 days becoming easily measureable from around 14 days onwards. As tHbmass increases, plasma volume begins to normalise, so both retics and [Hb] are normal. When you return from altitude, retics do not go below normal. With EPO though, after you stop the treatment retics will drop below normal almost immediately. With an infusion, the retics will also drop below normal immediately unless you continue to stimulate with EPO microdosing. So the response is quite different between altitude and doping.
 
Aug 9, 2009
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A few posts have alluded to producing EPO to more closely match the EPO produced by the human body. From the post by Cobber on the first page it shows the pic of the differences between Aranesp, rhEPO, and Endogenous EPO with regards to acidity. Is this what the EPO test is actually testing for, how acidic or base the EPO in the urine is? How hard can it be to produce something that falls in the range of Endogenous EPO? It seems like it would be almost trivial for a motivated lab to accomplish, and then those athletes connected with that lab would have a free pass until a new way of detecting it was available. Like with BALCO and the "clear". If a small lab like BALCO can produce an undetectable steroid doesn't it almost seem likely that there are similar small labs producing undetectable designer EPO right now?
 
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DonTickles said:
A few posts have alluded to producing EPO to more closely match the EPO produced by the human body. From the post by Cobber on the first page it shows the pic of the differences between Aranesp, rhEPO, and Endogenous EPO with regards to acidity. Is this what the EPO test is actually testing for, how acidic or base the EPO in the urine is? How hard can it be to produce something that falls in the range of Endogenous EPO? It seems like it would be almost trivial for a motivated lab to accomplish, and then those athletes connected with that lab would have a free pass until a new way of detecting it was available. Like with BALCO and the "clear". If a small lab like BALCO can produce an undetectable steroid doesn't it almost seem likely that there are similar small labs producing undetectable designer EPO right now?

Entirely possible. Would anyone take it? Consider that it has not run through a single clinical trial, probably no testing whatsoever? If your answer is yes, please change your middle name to 'guinea pig'.
 
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dopingectomy said:
from what I know about the CO rebreathing method, the problem is that the athlete is exposed to levels higher than the accepted threshold limit values:
http://www.osha.gov/SLTC/healthguidelines/carbonmonoxide/recognition.html

also, for technical reasons, it is extremely difficult to make the method compliant to the international standard for testing.

What is the needed CO concentration for the re-breather? AFAIR, cigarette smoke (inhaled) has about 2% CO (20,000 ppm). The OSHA standard is 50 ppm. Breath from smokers (when they're not smoking) has roughly 10-50 ppm CO and is very well measurable. Will the CO test introduce more CO than the smoke from one cigarette?
 
dopingectomy said:
from what I know about the CO rebreathing method, the problem is that the athlete is exposed to levels higher than the accepted threshold limit values:
http://www.osha.gov/SLTC/healthguidelines/carbonmonoxide/recognition.html

also, for technical reasons, it is extremely difficult to make the method compliant to the international standard for testing.

Are you referring to Autologous Blood Dope testing? or CO2 rebreathing devices?
 
Jul 31, 2009
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Cobblestones said:
Entirely possible. Would anyone take it? Consider that it has not run through a single clinical trial, probably no testing whatsoever? If your answer is yes, please change your middle name to 'guinea pig'.

I think a ton of people would take it. Just look at how many internet "pharmacies" there are selling steroids to every day people? There are a lot of gullible people out there willing to spend loads of money and risk their health on what is quite likely a low quality/no quality control Chinese lab knock off or outright fake. Once the first few riders take it and produce results without getting popped by a test then many others will follow. With how much some busted pro riders have stated they spent on doping it could be very profitable for a small lab.
 
Apr 12, 2009
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I thinks it's pretty clear, if you test positive for synthetic epo, your excuse shouldn't be you slept in an oxygen tent, any cyclist should know that, I knew that when I was racing and I never touched the stuff.
 
Jun 18, 2009
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DonTickles said:
A few posts have alluded to producing EPO to more closely match the EPO produced by the human body. From the post by Cobber on the first page it shows the pic of the differences between Aranesp, rhEPO, and Endogenous EPO with regards to acidity. Is this what the EPO test is actually testing for, how acidic or base the EPO in the urine is? How hard can it be to produce something that falls in the range of Endogenous EPO? It seems like it would be almost trivial for a motivated lab to accomplish, and then those athletes connected with that lab would have a free pass until a new way of detecting it was available. Like with BALCO and the "clear". If a small lab like BALCO can produce an undetectable steroid doesn't it almost seem likely that there are similar small labs producing undetectable designer EPO right now?

Cobblestones said:
Entirely possible. Would anyone take it? Consider that it has not run through a single clinical trial, probably no testing whatsoever? If your answer is yes, please change your middle name to 'guinea pig'.

I am not sure exactly how easy it would be to produce an endogenous-like EPO. Theoretically it is feasible, but I am not sure if it would be straight-forward. Given that the EPO drugs that have been produced do not resemble the endogenous EPO makes me think it would not be that straightforward to produce. It would depend on exactly which oligosaccharides are added to the EPO protein, by which cells, and whether this process if replicated can be scaled up for production.

However, the big question (from a pharma point of view) is why would a company do this if there is no market for it. Drug development for simple drugs can cost upwards of $500 billion. Is there a market for this in the pro cycling world? Probably not.... especially given that there are already several approved EPO drugs.
 
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Cobber said:
I am not sure exactly how easy it would be to produce an endogenous-like EPO. Theoretically it is feasible, but I am not sure if it would be straight-forward. Given that the EPO drugs that have been produced do not resemble the endogenous EPO makes me think it would not be that straightforward to produce. It would depend on exactly which oligosaccharides are added to the EPO protein, by which cells, and whether this process if replicated can be scaled up for production.

However, the big question (from a pharma point of view) is why would a company do this if there is no market for it. Drug development for simple drugs can cost upwards of $500 billion. Is there a market for this in the pro cycling world? Probably not.... especially given that there are already several approved EPO drugs.

I don't think the idea was for big pharma to produce another EPO-type product, fully FDA approved with all tests in order etc. I think he was talking about a mad scientist to copy and slightly modify the process by which EPO is produced nowadays to produce something closer to actual human EPO (close enough such that it won't show up on the synthetic EPO test). That person would then produce small quantities of the stuff and sell it on the black market (the stuff would never be tested, would never be scrutinized by the FDA etc. so it saves a lot of money.)

I don't know much about synthetic EPO production. So I really don't know how hard it would be. Maybe it's too difficult for a small lab.

On the other hand, before EPO could be synthesized, wasn't it harvested from the kidneys of dead people? Maybe the know-how is still there... That would be entirely 100% human EPO. I wonder how expensive such stuff would be.
 
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Synthesising endogenous EPO is very difficult

Current EPOs are not synthetic in the chemical sense, they are recombinant and purified from cultures of cells overproducing the protein. The basic protein structure is easy to control in this system and essentially all of the EPOs are identical in this sense. It is just that the cells also modify the protein by adding various sugar structures to it, this process is very difficult to control as we don't really understand it yet. Depending on the cell type (not just species bu tissue too) used to produce the EPO this will affect the sugar structures.

Even producing EPO using human cells (DynEPO, or others) versus the hamster origin cells (CHO) used for other EPOs still doesn't give you and endogenous like protein from a detection point of view although they all work biologically OK.
 
dopingectomy said:
from what I know about the CO rebreathing method, the problem is that the athlete is exposed to levels higher than the accepted threshold limit values:
http://www.osha.gov/SLTC/healthguidelines/carbonmonoxide/recognition.html

also, for technical reasons, it is extremely difficult to make the method compliant to the international standard for testing.
What international standard for testing are you referring to? Testing of what exactly? I don't see how would it differ from testing standards related to regular biochemical assay techniques such as ELISA or HPLC. Also, its hard to compare the exposure level to those recommendations in the OSHA document because they refer to 8hr averages, whereas the CO rebreathing method only lasts for 2mins.

cobblestones said:
What is the needed CO concentration for the re-breather? AFAIR, cigarette smoke (inhaled) has about 2% CO (20,000 ppm). The OSHA standard is 50 ppm. Breath from smokers (when they're not smoking) has roughly 10-50 ppm CO and is very well measurable. Will the CO test introduce more CO than the smoke from one cigarette?
The CO dose is 1 ml/kg BW. At the end of the test the CO concentration is measured in the lungs and it rarely goes above 30-40ppm. At this dose, the HbCO does not go above 6-7% and is more like 5% in endurance athletes, so the dose is roughly equivalent to smoking approx. 1-2 cigarettes. Things start getting dangerous once the HbCO gets up around 20%, so it is quite safe really.

The problem with the test is that it requires the athlete to comply with a set of instructions, but it is quite easy to sabotage the test by not complying with these instructions. So you could have an athlete that just pretends to be an unco-ordinated *** and always stuffs it up on purpose which would render the results useless. The only way around this problem is maybe to make it more of an inconvenience for the athlete and have them repeat the test every 24hr until they get it right. They'll learn pretty fast not to stuff it up if they know they'll just be back again and again and again.....