Transfusions and positives

[roundabout]

Thanks, now i have a mental image of Voet turning into the Incredible Hulk.

 

[bigloco]

We are never going to find the definitive evidence one way or another. Even if Contador's legal team tracks down some contaminated meat, we still won't know if it is an excuse. All we know is that the previous days' testing shows that the low level detected was not the result of declining values from a dose taken on a previous day. The positive definitely could have come from food contamination. It may be possible that it came from a transfusion.

I think what we can clearly say about this is that it shows the stupidity of not having a threshold for a positive. A quick bit of googling shows Clenbuterol contamination issues all over the world, everywhere from China to Turkey to Portugal. I don't know enough to say that the level that the level found for Contador should be too low to constitute a positive, but there surely exists a level that is too low. Anyone who handles money could be found positive for illegal drugs if the testing was sensitive enough.

I understand that, i thought maybe i was missing something in regards to the level and the vector which caused the positive.

 

[kurtinsc]

LMAO what a joke! Seriously, anyone with some serious knowledge of PEDs will completely discount that. It's about 100x more anabolic in animals than humans.

Unless I failed biology... I'm pretty certain humans are animals.

Just a FYI since you seemed to miss that fact on your way to a PHD.

 

[JRTinMA]

LMAO what a joke! Seriously, anyone with some serious knowledge of PEDs will completely discount that. It's about 100x more anabolic in animals than humans.

So you want us to believe you over two guys with a pretty impressive doping pedigree. You say you have a Phd (sic) in the biology field and they are world renowned dopers. I will stick with the experts thanks. Victor Conti and WV, you couldn't fill their jocks.

 

[hektoren]

And yet didn't I read that they had used an "undisclosed" procedure for testing blood in hopes of proving blood bag storage?

It may be all bs, but I'd definitely like to hear an official release of that data.

I don't know any specifics of the test or even if it really exists, but one would think they could differentiate DEHP leaching from a storage bag and that existing from ingestion.

Nope, you didn't read that. DEHP is just that. Di(2-ethylhexyl) phthalate, in short DEHP. Whether it's ingested, snorted, injected or a result of osmosis, it's still DEHP, and would show up as just that in blood, tissue or urine.

 

[Cobblestones]

Nope, you didn't read that. DEHP is just that. Di(2-ethylhexyl) phthalate, in short DEHP. Whether it's ingested, snorted, injected or a result of osmosis, it's still DEHP, and would show up as just that in blood, tissue or urine.

I just made a post in another thread about this. How do you know that, if ingested, DEHP enters the bloodstream?

 

[Merckx index]

I did indeed read your post. I was unable to find data on plasma or blood stability, I didn't say there wasn't data on metabolism and PK in vivo. Won't be the same at all in a bag.

I finally found a study that I think reports stability of CB in blood, but it costs money to get the full thing. In the meantime, FWIW it proves to be very stable in cold or frozen urine or liver tissue:

http://www.ncbi.nlm.nih.gov/pubmed/19138075

J Agric Food Chem. 2009 Feb 11;57(3):910-4.
Clenbuterol storage stability in the bovine urine and liver samples used for European official control in the azores islands (portugal).
Pinheiro I, Jesuino B, Barbosa J, Ferreira H, Ramos F, Matos J, da Silveira MI.
Laboratorio Regional de Veterinaria, Direccao de Servicos de Veterinaria, Direccao Regional do Desenvolvimento Agrario, Vinha Brava, Angra do Heroismo, Acores, Portugal.
Abstract
Clenbuterol is a well-known growth promoter, illegally used in farm animals, especially in cattle. Samples collected for the screening of beta(2)-agonist residues in Portuguese Azores Islands must travel through all the nine islands until they reach Azores Central Laboratory. If any suspicious sample is detected, it must be further transported to the National Reference Laboratory in Lisbon for confirmation. As a consequence of these circumstances, samples are submitted to different transport and storage times, as well as different temperature conditions and in some cases successive freezing and thawing cycles. As clenbuterol is the most detected beta(2)-agonist growth promoter in the Portuguese Residue Monitoring Plan, studies were conducted on the stability of this compound in incurred samples (bovine liver and urine) at +4, -20 and -60 degrees C over time. Samples kept at -20 degrees C were also analyzed over time after successive freezing and thawing cycles. The analyses of clenbuterol over time were performed by gas chromatography-mass spectrometry (GC-MS) with selected ion monitoring (SIM). Clenbuterol in incurred urine and liver samples was significantly stable up to 20 weeks at -20 and -60 degrees C and after, at least, six consecutive freezings and thawings. At +4 degrees C, clenbuterol remained stable, at least until 12 weeks in urine and up to 20 weeks in liver.

 

[131313]

So you want us to believe you over two guys with a pretty impressive doping pedigree. You say you have a Phd (sic) in the biology field and they are world renowned dopers. I will stick with the experts thanks. Victor Conti and WV, you couldn't fill their jocks.

Sorry, but a musician and a bike mechanic are suddenly experts in pharmacodynamics? Seriously, that's what it's come to here?

 

[hektoren]

It's not just the presence of DEHP, it's having "ten times over the higher value" of the stuff in his blood. That's surely highly suspicious whether it's grounds for a suspension or not (obviously not).

No, it's not suspicious at all. He eats more cling-film food in training and in competition than the most of us. Besides, he likes to sniff new cables.
Whaddya mean, suspicious? There's no baseline study to compare to, no protocol, no agreed threshold, no standard, this is new territory, this is think of a number, any number, your guess is as good as mine-land. In short: This is a dead end. Deader than a dodo.

 

[JRTinMA]

Sorry, but a musician and a bike mechanic are suddenly experts in pharmacodynamics? Seriously, that's what it's come to here?

Ok fine, how about Patrick Arnold, I think the point is valid. For the record I buy their stuff over a forum PhD. Doesn't matter anyway, Pharmador just tweeted we can trust him, its settled, he's clean. No way a 20yo stroke victim and a Puerto customer would ever lie.

 

[Escarabajo]

...
I don't doubt that blood samples were taken. In fact it would be absurd to not take a blood sample from the yellow jersey on the rest day before the queen stage. But it's likely that not as many blood samples were taken as urine samples. According to Contador's expert, Dr. Douwe de Boer, urine samples were taken every day between July 19 and 24. It's unlikely that blood samples were taken each of these days as well. Blood samples are more expensive to handle and analyze and repetitive blood sampling is intrusive to riders.

A close examination of his blood profile would still be useful.

I don't think they take blood samples on race days. i am fairly sure of that. It has been discussed here many times. It is because of the dehydration theory. They mostly do it on rest days (2 days). They build the profile with three samples mainly (2 rest days + the one right before the start). Plus the ones taken before during the training period.

 

[hektoren]

I just made a post in another thread about this. How do you know that, if ingested, DEHP enters the bloodstream?

Easy-peasy: It does, and it's proven beyond doubt through any number of tests. Ingest it, and it shows up in your bloodstream. It has been mentioned in connection with hormone disruption, as a chemical that might disrupt the production of human hormones, it's banned in children's toys, etc. etc. etc.
Look it up. Do some double-ought-investigation googling and you'll see.

 

[Escarabajo]

This is what Willy Voet had to say about clenbuterol.

.... The Clenbuterol had been eliminated from my system by day eight. For a cyclist, who will get rid of chemicals far more quickly than someone sedentary like me, the period was still shorter.

And the effects were felt almost immediately. Three hours after I took the first pill, I began shivering. I had the impression that my lungs were swelling, that I had a new battery somewhere in the system. I felt confident, full of energy, strong as a bull - on hormones. The effects lasted for more than a month, effects which we used with good results in the big Tours after that.

some quotes from Victor Conte talking about this drug

Quote:
“It has faster clearance than any of the anabolic steroids, and it's an anabolic substance,”

“It will accelerate healing and tissue. It could also be used as a stimulant but would more likely be used between events to enhance recovery.”


http://www.bikeradar.com/forum/viewtopic.php?p=16508093

Thanks.

This is it. I thought Wiki was enough.

If it wasn't good and potent why more athletes keep popping up positive for this drug.

 

[cyclanalyst]

I finally found a study that I think reports stability of CB in blood, but it costs money to get the full thing. In the meantime, FWIW it proves to be very stable in cold or frozen urine or liver tissue:
...snip...
At +4 degrees C, clenbuterol remained stable, at least until 12 weeks in urine and up to 20 weeks in liver.[/B]

Good addition to the knowledge base. Someone should set up a Contador wiki!

It think it's becoming obvious that if clen were in his blood bags it would end up in his urine. It still seems like a rookie mistake to me, given that whoever was in charge of a (putative) blood doping plan would have known about his clen cycle.

From what I can tell from the literature, in 1997 the routine limit of quantitation (LOQ) was about 0.2 ng/mL, and now the better labs can do 0.01 ng/mL (same I think by either immunoassay or LC/MS/MS). That may mean that his "doctor" based his plan on outdated info, or didn't expect the samples to be sent to Cologne.

I dunno, earlier today I would have voted for meat, but now I'm not so sure...

 

[hektoren]

Good addition to the knowledge base. Someone should set up a Contador wiki!

It think it's becoming obvious that if clen were in his blood bags it would end up in his urine. It still seems like a rookie mistake to me, given that whoever was in charge of a (putative) blood doping plan would have known about his clen cycle.

From what I can tell from the literature, in 1997 the routine limit of quantitation (LOQ) was about 0.2 ng/mL, and now the better labs can do 0.01 ng/mL (same I think by either immunoassay or LC/MS/MS). That may mean that his "doctor" based his plan on outdated info, or didn't expect the samples to be sent to Cologne.

I dunno, earlier today I would have voted for meat, but now I'm not so sure...

Actually, it's not a good idea to add literature concerning BOVINE experiments with Clenbuterol in a knowledge-base pertaining to pro-cycling. It'd be a lot better if the real scientists contribute here, not an amoeba who has deciphered the modus operandi of Google.

 

[Merckx index]

It think it's becoming obvious that if clen were in his blood bags it would end up in his urine.

I think a reasonable "what if" assumption at this point is that all the CB in any withdrawn blood is retained during storage, and enters the bloodstream intact during a hypothetical re-infusion. There may be enzymes in blood that metabolize it, but since it is a synthetic ligand, apparently many of the usual transformations are not possible (the link I previously posted). And you would think that storage in liver tissue would maximize metabolism, though not having read the full article, I don't know what form this tissue was in, how easily liver enzymes could have accessed CB.

But if we assume that most CB in stored, re-infused blood remains intact, then the transfusion possibility is supported IF AC took CB at some point in the past. He wouldn't have had to have much in his system in order that a unit or two from that system put enough back in to test at 50 pg/ml in the urine.

From what I gather from those who know more about its use in the peloton, though, this is not really likely. AC would not take CB at all. Hence I throw out the strange but now plausible theory that AC picked up the CB some time before the Tour in contaminated meat, then withdrew/transfused later.

One can argue that once the contaminated meat possibility is on the table, why not just say that he got it at the Tour, and leave it at that? Fair enough, except that eating contaminated meat has to be considered a pretty low probability event. If it could have happened at any time during a long period prior to the Tour, it becomes a little more likely.

 

[Merckx index]

Actually, it's not a good idea to add literature concerning BOVINE experiments with Clenbuterol in a knowledge-base pertaining to pro-cycling. It'd be a lot better if the real scientists contribute here, not an amoeba who has deciphered the modus operandi of Google.

FWIW, I do research in pharmacology, among other things, and animal studies are certainly relevant to human physiology. When there are human data, of course they're preferred, but sometimes they aren't available. As long as the distinction is noted, no real problem.

And a dirty little secret in our profession is that often google scholar is a better source than Pub Med.

 

[hektoren]

FWIW, I do research in pharmacology, among other things, and animal studies are certainly relevant to human physiology. When there are human data, of course they're preferred, but sometimes they aren't available. As long as the distinction is noted, no real problem.

And a dirty little secret in our profession is that often google scholar is a better source than Pub Med.

Well, bovine studies would never form the knowledge-base for regulations of admissible concentration of ANY drug under WADA-UCI-IOC rules. If you do research in pharma you'd know.
Bovine studies may give you a pointer as to the general direction, check, but as (for example) the anabolic effect of Clenbuterol is more evident in cattle than among our brethren, you, as a scientist only referring to bovine studies, couldn't give the time of day to WADA.

 

[python]

Well, bovine studies would never form the knowledge-base for regulations of admissible concentration of ANY drug under WADA-UCI-IOC rules. If you do research in pharma you'd know.
Bovine studies may give you a pointer as to the general direction, check, but as (for example) the anabolic effect of Clenbuterol is more evident in cattle than among our brethren, you, as a scientist only referring to bovine studies, couldn't give the time of day to WADA.

you're making an important point. as i said before, clenbuterol's classification as an anabolic in the wada banned list is (to say the least) controversial if one concern's only with human studies. in fact, the most frequently heard anecdotal effect of clen on endurance athletes is similar to stimulants and amphetamines. the anabolic effects of clen on humans vs, cattle or horses is fairly poorly studied. iirc, the half life is also quite different - 10-100 hours vs. 24-32 h with horses being on the shorter end of the range

 

[Merckx index]

Well, bovine studies would never form the knowledge-base for regulations of admissible concentration of ANY drug under WADA-UCI-IOC rules. If you do research in pharma you'd know.
Bovine studies may give you a pointer as to the general direction, check, but as (for example) the anabolic effect of Clenbuterol is more evident in cattle than among our brethren, you, as a scientist only referring to bovine studies, couldn't give the time of day to WADA.

Let me break the news to you. This is a forum, where we speculate. Nothing said here is going to sway WADA in the slightest. Nor should it.

Specifically, our discussion here is just trying to evaluate the possibility that Bert's positive was from a blood transfusion. Nobody but Bert can answer this question with certainty, but certain data, some of it perhaps from animals, may give us reason to come to some personal conclusion about what most likely happened.

E.g., if the only data on CB stability in plasma were from some mammalian species, and it was found that it was highly stable for several weeks in the cold, I would take that to mean it was quite likely that it would also be the case in human plasma. If studies with several different mammalian species all provided the same results, I would be even more confident of this conclusion. I might then be inclined to put this conclusion together with other factors, suggesting doping.

In fact, I don't think it will come to this. I'm pretty sure the human studies have been done. But even if they have, the results are only of relevance to us in the forum. I can't see how WADA would be interested in them, because all they do is make it more or less likely that blood transfusion could have been the source of the CB. In the absence of any direct evidence for transfusion, WADA can't use arguments like that, even though those of us in this forum certainly can, and some of us will.

All WADA/UCI can do is decide how likely it was that the CB came from contaminated food, and if it did, whether that matters. No matter how easy or how difficult it might turn out that blood doping could explain the positive, I don't see how that could sway WADA's decision in either direction.

 

[cyclanalyst]

Let me break the news to you. This is a forum, where we speculate. Nothing said here is going to sway WADA in the slightest. Nor should it.

Specifically, our discussion here is just trying to evaluate the possibility that Bert's positive was from a blood transfusion. Nobody but Bert can answer this question with certainty, but certain data, some of it perhaps from animals, may give us reason to come to some personal conclusion about what most likely happened.

E.g., if the only data on CB stability in plasma were from some mammalian species, and it was found that it was highly stable for several weeks in the cold, I would take that to mean it was quite likely that it would also be the case in human plasma. If studies with several different mammalian species all provided the same results, I would be even more confident of this conclusion. I might then be inclined to put this conclusion together with other factors, suggesting doping.

I absolutely agree. I don't need to see stability data from human blood. We draw reasonable conclusions from surrogate or analogous measurements all the time. Many with science backgrounds are aware that enzymatic degradation shuts down (not slows down) at low temperature, and that oxidative degradation is very slow and limited. If it's stable at 12 weeks in bovine, you can expect at worst minimal degradation in human blood at 4C.

I also think that those of us who've been speculating based on available science have been careful to qualify our statements. It's obvious to me that we've been speculating about whether the meat or the blood bag hypotheses are plausible, not whether they're true.

I'm still stuck at this point: why would AC be using clen at all? Even if you assume he used blood doping techniques, it still doesn't make sense to use this particular drug at any time in a training or racing period. Too narrow a therapeutic window, too well-known, too easily detected, and too long-lived. This is not a doping product for the top ranks.

 

[SlowBloke]

Hopefully

Let me break the news to you. This is a forum, where we speculate. Nothing said here is going to sway WADA in the slightest. Nor should it.

....

All WADA/UCI can do is decide how likely it was that the CB came from contaminated food, and if it did, whether that matters. No matter how easy or how difficult it might turn out that blood doping could explain the positive, I don't see how that could sway WADA's decision in either direction.

Unless the extended testing that they have said they are doing is to investigate the possibility that the CB presence is a pointer to the transfusion.

Personally I think this, along with the statements made by Landis about his doping (I didn't do the testosterone patch thing, I was transfusing, so they fitted me up), indicate a potential line of transfusion testing that the science will be focused on quite heavily in the coming months.

 

[Escarabajo]

...

I'm still stuck at this point: why would AC be using clen at all? Even if you assume he used blood doping techniques, it still doesn't make sense to use this particular drug at any time in a training or racing period. Too narrow a therapeutic window, too well-known, too easily detected, and too long-lived. This is not a doping product for the top ranks.

Or maybe he ate the meat during training.

The fact that he arranged the story that the meat came from a friend, in spain, blah, blah, blah, is what made me skeptical.

There is the story from Willy Voet about this drug which indicates that it really works and that it leaves the system very fast on athletes. So we can not ignore that.

 

[Joey_J]

It's not just the presence of DEHP, it's having "ten times over the higher value" of the stuff in his blood. That's surely highly suspicious whether it's grounds for a suspension or not (obviously not).

you would think that cyclists have a higher than normal level of plastic and chemicals from plastic in their blood/urine since they are exposed to more plastic than a normal person. These guys are drinking out of plastic water bottles 24/7

http://trusted.md/blog/vreni_gurd/2007/03/29/plastic_water_bottles#axzz1170njxDj

 

[mastersracer]

you would think that cyclists have a higher than normal level of plastic and chemicals from plastic in their blood/urine since they are exposed to more plastic than a normal person. These guys are drinking out of plastic water bottles 24/7

http://trusted.md/blog/vreni_gurd/2007/03/29/plastic_water_bottles#axzz1170njxDj

non-issue - it would be deviations from some baseline.