Effects of EPO on blood parameters and running performance in Kenyan athletes

Introduction: Recombinant human erythropoietin (rHuEpo) administration enhances oxygen carrying capacity and performance at sea level. It remains unknown whether similar effects would be observed in chronic altitude-adapted endurance runners. The aim of this study was to assess the effects of rHuEpo on hematological and performance parameters in chronic altitude-adapted endurance runners as compared to sea level athletes. Methods: Twenty well-trained Kenyan endurance runners (KEN) living and training at approximately 2150 m received rHuEpo injections of 50 IU·kg−1 body mass every 2 d for 4 wk and responses compared with another cohort (SCO) that underwent an identical protocol at sea level. Blood samples were obtained at baseline, during rHuEpo administration and 4 wk after the final injection. A maximal oxygen uptake (V˙O2max) test and 3000-m time trial was performed before, immediately after and 4 wk after the final rHuEpo injection. Results: Hematocrit (HCT) and hemoglobin concentration (HGB) were higher in KEN compared to SCO before rHuEpo but similar at the end of administration. Before rHuEpo administration, KEN had higher V˙O2max and faster time trial performance compared to SCO. After rHuEpo administration, there was a similar increase in V˙O2max and time trial performance in both cohorts; most effects of rHuEpo were maintained 4 wk after the final rHuEpo injection in both cohorts. Conclusions: Four weeks of rHuEpo increased the HGB and HCT of Kenyan endurance runners to a lesser extent than in SCO (~17% vs ~10%, respectively) and these alterations were associated with similar improvements in running performance immediately after the rHuEpo administration (~5%) and 4 wk after rHuEpo (~3%)

Validation of whole-blood transcriptome signature during microdose recombinant human erythropoietin (rHuEpo) administration

BACKGROUND: Recombinant human erythropoietin (rHuEpo) can improve human performance and is therefore frequently abused by athletes. As a result, the World Anti-Doping Agency (WADA) introduced the Athlete Biological Passport (ABP) as an indirect method to detect blood doping. Despite this progress, challenges remain to detect blood manipulations such as the use of microdoses of rHuEpo. METHODS: Forty-five whole-blood transcriptional markers of rHuEpo previously derived from a high-dose rHuEpo administration trial were used to assess whether microdoses of rHuEpo could be detected in 14 trained subjects and whether these markers may be confounded by exercise (n = 14 trained subjects) and altitude training (n = 21 elite runners and n = 4 elite rowers, respectively). Differential gene expression analysis was carried out following normalisation and significance declared following application of a 5% false discovery rate (FDR) and a 1.5 fold-change. Adaptive model analysis was also applied to incorporate these markers for the detection of rHuEpo. RESULTS: ALAS2, BCL2L1, DCAF12, EPB42, GMPR, SELENBP1, SLC4A1, TMOD1 and TRIM58 were differentially expressed during and throughout the post phase of microdose rHuEpo administration. The CD247 and TRIM58 genes were significantly up- and down-regulated, respectively, immediately following exercise when compared with the baseline both before and after rHuEpo/placebo. No significant gene expression changes were found 30 min after exercise in either rHuEpo or placebo groups. ALAS2, BCL2L1, DCAF12, SLC4A1, TMOD1 and TRIM58 tended to be significantly expressed in the elite runners ten days after arriving at altitude and one week after returning from altitude (FDR > 0.059, fold-change varying from 1.39 to 1.63). Following application of the adaptive model, 15 genes showed a high sensitivity (≥ 93%) and specificity (≥ 71%), with BCL2L1 and CSDA having the highest sensitivity (93%) and specificity (93%). CONCLUSIONS: Current results provide further evidence that transcriptional biomarkers can strengthen the ABP approach by significantly prolonging the detection window and improving the sensitivity and specificity of blood doping detection. Further studies are required to confirm, and if necessary, integrate the confounding effects of altitude training on blood doping

Haemoglobin mass and running time trial performance after recombinant human erythropoietin administration in trained men

<p>Recombinant human erythropoietin (rHuEpo) increases haemoglobin mass (Hbmass) and maximal oxygen uptake (v˙ O2 max).</p> <p>Purpose: This study defined the time course of changes in Hbmass, v˙ O2 max as well as running time trial performance following 4 weeks of rHuEpo administration to determine whether the laboratory observations would translate into actual improvements in running performance in the field.</p> <p>Methods: 19 trained men received rHuEpo injections of 50 IUNkg21 body mass every two days for 4 weeks. Hbmass was determined weekly using the optimized carbon monoxide rebreathing method until 4 weeks after administration. v˙ O2 max and 3,000 m time trial performance were measured pre, post administration and at the end of the study.</p> <p>Results: Relative to baseline, running performance significantly improved by ,6% after administration (10:3061:07 min:sec vs. 11:0861:15 min:sec, p,0.001) and remained significantly enhanced by ,3% 4 weeks after administration (10:4661:13 min:sec, p,0.001), while v˙ O2 max was also significantly increased post administration (60.765.8 mLNmin21Nkg21 vs. 56.066.2 mLNmin21Nkg21, p,0.001) and remained significantly increased 4 weeks after rHuEpo (58.065.6 mLNmin21Nkg21, p = 0.021). Hbmass was significantly increased at the end of administration compared to baseline (15.261.5 gNkg21 vs. 12.761.2 gNkg21, p,0.001). The rate of decrease in Hbmass toward baseline values post rHuEpo was similar to that of the increase during administration (20.53 gNkg21Nwk21, 95% confidence interval (CI) (20.68, 20.38) vs. 0.54 gNkg21Nwk21, CI (0.46, 0.63)) but Hbmass was still significantly elevated 4 weeks after administration compared to baseline (13.761.1 gNkg21, p<0.001).</p> <p>Conclusion: Running performance was improved following 4 weeks of rHuEpo and remained elevated 4 weeks after administration compared to baseline. These field performance effects coincided with rHuEpo-induced elevated v˙ O2 max and Hbmass.</p&gt

Binary alloys and control with compared phase diagrams and mean atom volumina

A comparative classification of the binary intermetallic systems is presented as a possible control of the known phase diagrams by comparison of the mean atom volumina in alloys

Single-metal deposition: optimization of this fingermark enhancement technique

Following the introduction of single-metal deposition (SMD), a simplified fingermark detection technique based on multimetal deposition, optimization studies were conducted. The different parameters of the original formula were tested and the results were evaluated based on the contrast and overall aspect of the enhanced fingermarks. The new formula for SMD was found based on the most optimized parameters. Interestingly, it was found that important variations from the base parameters did not significantly affect the outcome of the enhancement, thus demonstrating that SMD is a very robust technique. Finally, a comparison of the optimized SMD with multi-metal deposition (MMD) was carried out on different surfaces. It was demonstrated that SMD produces comparable results to MMD, thus validating the technique