Se ha detectado factores de crecimiento fibroblásticos falsificados con fines ilegales. Fundamentalmente remedar la accion anabolizante contrainsular de la somatotropina o de algunos de sus factores de crecimiento.Se transcribe literalmente el artículo en su versión original puesto que al no existir fronteras legalmente pueden entrar desde Alemania a nuestro país.
Innecesario decir que para la detección de éstas sustancias hacen falta técnicas sofisticadas de las que adolecemos en éstos momentos en nuestro laboratorio....la electroforesis en gel.
Director Wilhelm Schanzer and his staff run the World Anti-Doping Agency (WADA) accredited facility. Here, they conduct research into potential drugs of abuse and their metabolites and devise analytical methods for them.They are also asked to help identify unknown substances that have been seized by the authorities, as was the case recently when German customs presented them with a set of samples which they had confiscated. The injection vials contained a colourless lyophilisate but were sealed and unlabelled, so the there were no clues as to the contents.
An initial analysis by SDS-PAGE indicated that the samples contained several proteins, so a proteomics approach was instigated to identify the components present. The work was carried out by Schanzer, Mario Thevis and colleagues at their lab, along with coresearchers from the Centre for Education and Science of the Federal Revenue Administration, Cologne, the Heinrich Heine University of Dusseldorf and the Anti-Doping Authority of Portugal, Lisbon.
Gel electrophoresis revealed the presence of several proteins up to molecular mass 150 kDa, which were identified by mass spectrometry. Characteristic human plasma components like albumin, haptoglobin, and hemopexin were found, along with a band corresponding to fibroblast growth factor 1 (FGF-1).
Growth in illegal growth factors
The FGF-1 family of proteins are widely expressed in tissues and cells and have been implicated in a wide range of physiological processes. These include muscle and wound healing and regeneration, bone regeneration, tendon and ligament repair and the growth of new blood vessels (angiogenesis).
Athletes have been known to take insulin-like growth factor 1 and growth hormone releasing peptides as performance enhancing drugs. Based on these observations, WADA has placed a group of growth factors on its prohibited list, despite the fact that some of them, such as FGF-1, have not been approved for full clinical use. This omission has not deterred athletes in the past.
Having established its presence, the researchers decided to take a closer look at the structure of FGF-1 from the black market product.
Samples of recombinant human FGF-1 and the black market product were compared by SDS-PAGE, which showed that the illicit form had a slightly lower molecular mass than the recombinant form. On further inspection by enzymatic digestions and mass spectrometric analysis, it was revealed that the N-terminus of the black market product had been truncated or modified.
FGF-1 from the black market
The amount of FGF-1 in the product was measured both by SDS-PAGE using a light transmission scanner and by a specific ELISA. The corresponding concentrations were 1.9 and 1.6 µg per injection vial, respectively.
It is useful to know these values, but they do not mean an awful lot at this stage because therapeutic levels have not yet been established. But for comparison, the researchers measured the levels of natural FGF-1 in the plasma and urine of 15 healthy volunteers.
In fact, FGF-1 was undetectable in plasma and was found in only 8 of the 15 urine samples at concentrations less than 28 pg/mL. These low levels were expected, due to the strong binding of FGF-1 to proteoglycans in vivo to protect it against degradation by proteases, to which it is particularly susceptible.
In theory, the black market lyophilisate could be used in cosmetics as an anti-aging product but the team concluded that this was unlikely, since cosmetics are generally in a form to be applied topically.
The most likely purpose is for illicit use as a performance enhancing drug, probably via intramuscular or subcutaneous injection, despite the potential dangers to the user from the absence of clinical data for suitable dosages of FGF-1.
This study emphasises the value of organisations such as the Centre for Preventive Doping Research which have to be proactive in doping research and be prepared to attack the problem from different angles, in anticipation of the next new illicit drug to hit the black market.