Raynald Gareau

Effects of erythropoietin administration in training athletes and possible indirect detection in doping control

PURPOSE This study investigated the effects of repeated subcutaneous injection of rHuEpo (50 IU x kg(-1)) in athletes and proposes a method based on the measurement in blood samples of the sTfR/serum protein ratio to determine if the observed values of this marker are related to rHuEpo abuse. METHODS Serum erythropoietin concentrations, and hematological and biochemical parameters were evaluated, during treatment and for 25 d posttreatment in nine training athletes. Moreover, the effect of rHuEpo administrations on the maximum oxygen uptake (VO2max) and ventilatory threshold (VT) of these athletes was also studied. Threshold values for sTfr and the sTfr/serum protein ratio were determined from 233 subjects (185 athletes, 15 athletes training at moderately high altitude, and 33 subjects living at >3000 m). RESULTS Significant changes in reticulocytes, hemoglobin (Hb) concentration, hematocrit (Hct), sTfr, and sTfr/serum proteins were observed during and after rHuEpo treatment. The maximal heart rate of 177 beats x min(-1) at the beginning of the study was significantly higher than the value of 168 beats x min(-1) after 26 d of rHuEpo administration. Compared with the values measured at baseline, the VT measured after rHuEpo administration occurred at a statistically significant high level of oxygen uptake. CONCLUSIONS When oxygen uptake measured at the VT was expressed as a percentage of V02 max, the values obtained were also significantly higher. The increased values of Tfr and sTfr/serum proteins, respectively, above 10 microg x mL(-1) and 153, indicated the probable intake of rHuEpo.

Inhibition of the interaction between lipoproteins and amphotericin B by some delivery systems

Amphotericin B (AmB) is a potent antifungal agent used to treat patients with systemic mycoses. The clinical usefulness of the drug is limited by its high toxicity and several new less toxic formulations of AmB have been recently developed. In order to understand the mechanism of the decreases of toxicity caused by various new delivery systems, we have investigated by uv-visible spectroscopy the interaction of two of these formulations with human blood lipoproteins. The results were compared with those obtained with the commonly used pharmaceutical form of AmB (Fungizone). This study shows that AmB-lipoprotein interaction is hindered when the drug is in a monomeric form and/or when it is included in phospholipid-surfactant micelles. In an in vivo study on mice it is shown here that AmB monomerized by surfactant is less toxic to animals than the same concentration of Fungizone, where the polyene is strongly aggregated. It may be concluded from the present study that the AmB species which is responsible for the in vivo toxicity is a complex of the antibiotic with the low density and the very low density blood lipoproteins and that hindering of this complex formation results in a decrease of AmB toxicity.

Total Fibrin and Fibrinogen Degradation Products in Urine: A Possible Probe to Detect Illicit Users of the Physical-Performance Enhancer Erythropoietin?

Erythropoietin (Epo) represents for some athletes the ultimate tool to gain an edge over their peer competitors. Underground information indicates that its usage is spreading at an epidemic pace since no analytical technique is yet available to detect its utilization. We hereby report observations obtained from analysis of urine specimens collected from top-level athletes after international-calibre competitions. Possible Epo misuse was evaluated by the measurement of urine total degradation products (TDPs), excretory fragments attributed by Sakakibara et al. to the fibrinolytic action of Epo. Markedly elevated urine TDP levels were measured in more than 13% of the 76 top-level athletes evaluated in this study. Analyses of urine specimens from a control hockey player group and from out-of-competition resting subjects indicate that the urine TDP content is not significantly influenced by exercise per se. Solid confirmation of TDP measurement as a sound probe to detect illicit Epo users should come from controlled studies with concomitant administration of Epo.