Abstract

Human cells are constantly in need of oxygen that is delivered by erythrocytes to every tissue. The production of erythrocytes is stimulated and regulated by erythropoietin (Epo), a glycoprotein growth factor which is produced mainly by the kidneys. This molecule has a globular protein portion and a glucidic portion which does not act on the target cells but increases the half-life of the Epo. Fifteen years ago, the human Epo gene was cloned and so a synthetic hormone almost identical to human Epo was available for therapeutic use. The main clinical indication to use recombinant human Epo (rHuEpo) is the treatment for severe anemia associated with chronic renal failure. This drug may also be used for anemia associated with zidovudine or cis-platin therapy and in surgical patients, to increase erythropoiesis before elective surgery. With regard to Epo-doping, we have to say first of all that in several sporting discipline the most important factor in performance is the maximal aerobic power, that is the amount of oxygen available to satisfy the requirements of active musculature. It is possible to increase the aerobic power through blood infusion but now the rHuEpo use is preferred compared to the homologous transfusion and autohemotransfusion. Endurance athletes use rHuEpo to enhance their performance but this illicit use of erythropoietin exposes to unacceptable risks, linked mainly to blood hyperviscosity. Since 1990, recombinant human erythropoietin is on the International Olympic Committee list of banned substances, but at the moment Epo-doping is still a widespread and uncontrollable phenomenon. It is not easy to disclose rHuEpo administration because there is a strong homology between natural and exogenous Epo, and because rHuEpo has a short plasm half-life while its erythropoietic effects are delayed. So it becomes essential the research of indirect signs of abuse, but this practice presents a fundamental limit: for a certainty it will not be able to make charge of Epo-doping against an athlete with hematocrit above the determinate limit as well as is not possible to accuse an athlete to make use of anabolic substances only on the ground of an abnormal development of the muscular mass. Among the indirect parameters it is necessary to point out, besides the values of hematocrit and of the hemoglobin, the concentration of serum soluble receptors whose increase represents the indirect sign more reliable of Epo abuse. Epo natural molecule undergoes glycosilation after the transcription; exogenous molecule does not: that's why their electrophoretic mobility properties are different. Taking advantage of this structural microheterogeneity, the French group directed by Lasne F and de Ceaurriz J developed a new analytic technique aimed at detecting the rHuEpo in urine. This technique consists in a chemiluminescent immunodetection after isoelectric focusing and it is very quick, neither invasive nor expensive; but there are some limits: it is possible to detect recent exposures only and urinary rHuEpo concentration has to be high. Verf.-Referat