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Biomedical subjects

R Gareau

Publications and source records attributed to R Gareau.

At least 19 recordsLinked to original sources
PubMed1998

Erythropoietin (rHuEPO) doping: effects of exercise on anaerobic metabolism in rats.

The purpose of this study was to investigate the effects of recombinant human erythropoietin (rHuEPO) administration on energy metabolism during exercise. Specifically, the contribution of anaerobic (glycogen) metabolism during exercise was evaluated. Sprague-Dawley rats were randomly assigned to an experimental [rHuEPO] (600 U x kg(-1) of Eprex, every 3 days) or control (equivalent volume of saline) group. After 15 days of treatment, animals from both groups were randomly subjected to either a 30-minute exercise (swimming with 5% body weight added) or resting period. They were sacrificed at the end of the exercise period. Their liver and muscles were quickly removed and frozen in liquid nitrogen. Blood was also sampled. rHuEPO administration resulted in a significant (P < 0.05) increase of hematocrit (from 42 +/- 2 to 54 +/- 7 L/L). In the rHuEPO group, both muscle glycogen and free fatty acids were higher whereas lactate was lower at the conclusion of the exercise period (P < 0.05). These results suggest that energy substrate utilization during exercise is affected by enhanced oxygen availability. Finally, a lower overall contribution to energy production from anaerobic metabolism during exercise followed rHuEPO administration.

Analysis of Variance↗
PubMed1997

Influence of a transscrotal testosterone propionate administration on the serum level of selected hormones of the hypophyso-gonadal axis.

This study was designed to examine the effect of a percutaneous scrotal administration of testosterone propionate (TP) on selected blood variables, in order to identify a reliable anti-doping probe liable to disclose the illicit use of testosterone. Twelve healthy adult males gave their informed consent for the study. Each morning (8:30) and for 10 consecutive days (D), a placebo (D:1,2,3,...8,9,10) or a testosterone propionate (200mg TP on D:... 4,5,6,7...) scrotal patch was installed. On D2 or D3 (placebo-treated) or D7 (TP-treated), venous blood samples were collected at 5 min intervals from 9:00 until 13:00. Serum LH, FSH, 17alpha-hydroxyprogesterone (17HP), testosterone (T), estradiol (E2) and SHBG contents were analysed by immunoassays. The high sampling frequency revealed that TP was associated with the complete abolition of serum LH pulses. Although statistically significant, TP treatment was not related to explicit changes in serum FSH, E2, T/E2 and T/SHBG. TP-induced effects were most significant on serum LH, T and 17HP and were most clearly illustrated by a bi-dimensional distribution plot of serum values of the latter variables. The expression of a combination of the latter parameters could eventually serve to detect testosterone misusers.

17-alpha-Hydroxyprogesterone↗
PubMed1997

Comparison of a direct and indirect population pharmacodynamic model: application to recombinant human erythropoietin in athletes.

Basic physiologic indirect response models have been proposed to account for the pharmacodynamics of drugs that act by way of inhibition or stimulation of the production or loss of endogenous substances or mediators. In this work, these models were applied to account for the effects of recombinant human erythropoietin (rHuEpo) in man. Indeed, rHuEpo induces a delayed increase of serum soluble transferrin receptors (sTfr) and a delayed decrease in ferritin (fr) concentrations. The purpose of the present study was to compare two pharmacodynamic approaches to relate serum erythropoietin (Epo) concentrations to the effect of rHuEpo on sTfr, and fr, the "indirect effect" and the "effect compartment" models. However, due to the average lag time of about 50 hr between the first intake of rHuEpo and the onset of the measurable effects, a delay function was incorporated into the "indirect response models" to describe the relationship between the Epo plasma concentrations and the endogenous receptors or mediators affected by the drug and responsible for the effects on sTfr and fr. There are no real differences in the descriptive features of the two models used. For these reasons, the indirect model seems more appropriate because it supplies a possible mechanistic interpretation of the physiological process.

Adult↗
PubMed1997

Frequent serum sampling in healthy men discloses testosterone peaks exacerbated by testosterone propionate administration.

Interval samplings uncover blood diurnal oscillations for several hormones, highlighting the importance of short time intervals in the disclosure of subtle pulsatile patterns of some peptide hormones, namely LH. In a study designed to develop new probes against steroid misuse, venous blood was sampled at 5-min intervals for 4 hours from 12 eugonadal adult male athletes, 6 receiving transcutaneous administrations of testosterone propionate and 6 placebo subjects. Brief supraphysiologic serum testosterone peaks were disclosed, the amplitude and frequency of these peaks being larger for the treated group. No solid explanation could be given to explain these bursts. Neither the binding/dissociation kinetics of SHBG molecules with and without increased circulating level of dihydrotestosterone, nor brief testosterone-inducing LH bursts, nor increased Leydig cell release could be invoked to explain these peaks. Their occurrence, although relatively rare, could represent a threat and lead to improper treatment.

Administration, Cutaneous↗
PubMed1996

Pharmacokinetics and haematological parameters of recombinant human erythropoietin after subcutaneous administrations in horses.

The pharmacokinetics of recombinant human Epo (rHuEpo) were investigated after subcutaneous administration to horses. Four horses received a single 30IU kg-1 dose of rHuEpo. One horse received three repeated doses of 120 IU kg-1 at 48 h intervals. Plasma erythropoietin (Epo) was measured by radioimmunoassay. In both cases pharmacokinetic parameters were evaluated using a one-compartment open model and first-order input and output rates. The mean values (+/-SD) for elimination half-life, CL/F, and Vd/F after a single dose were 12.9 +/- 3.34 h, 11.8 +/- 4.96 L h-1, and 233 +/- 126 L, respectively. After repeated doses, elimination half-life, CL/F, and Vdss/F were 11.3 h, 8.94 L h-1, and 145.6 L, respectively. No significant differences were observed between the haematological parameters after a single 30 IU kg-1 administration compared to baseline values. Multiple and high doses of rHuEpo modified red blood cells, haemoglobin, and hematocrit. According to our results, plasma Epo assay can help, during an antidoping control procedure, to support a positive result only up to 72 h after the last rHuEpo.

Animals↗
PubMed1996

Pharmacokinetics and pharmacodynamics of recombinant human erythropoietin in athletes. Blood sampling and doping control.

1. The pharmacokinetics of recombinant human erythropoietin (rHuEpo) were initially determined in two healthy volunteers after a single subcutaneous dose (50 u kg-1). Twenty subjects then received repeated subcutaneous administrations of high dose (200 u kg-1) rHuEpo and 10 subjects received placebo. An immunoradiometric assay was used to measure the concentrations of erythropoietin (Epo) in serum and urine. 2. Serum Epo concentration-time profiles were best described by a one-compartment open model with zero-order input. The mean elimination half-life (+/- s.d.) was 42.0 +/- 34.2 h. Clearance, uncorrected for bioavailability, was 0.05 +/- 0.011 h-1 kg-1. Erythropoietin concentrations returned to normal values in serum and urine, 7 and 4 days after the last administration, respectively. 3. The recombinant hormone was well tolerated. Significant changes in reticulocytes and red blood cells, haemoglobin concentrations and haematocrit were observed after administration of rHuEpo. In the control group, these parameters remained unchanged. 4. The change in reticulocytes was used as an index of the therapeutic effect of rHuEpo. The concentration-effect relationship was best described by an exponential model. 5. These data show the limitations of the measurement of Epo concentrations in blood and urine samples, collected in athletes during competition, for antidoping control. Epo doping can be detected only during or within 4 to 7 days of ending a course of rHuEpo.

Adult↗
PubMed1995

Effects of exercise during normoxia and hypoxia on the growth hormone-insulin-like growth factor I axis.

The response of plasma insulin-like growth factor I (IGF I) to exercise-induced increase of total human growth hormone concentration [hGHtot] and of its molecular species [hGH20kD] was investigated up to 48 h after an 1-h ergometer exercise at 60% of maximal capacity during normoxia (N) and hypoxia (H) (inspiratory partial pressure of oxygen = 92 mmHg (12.7 kPa); n = 8). Lactate and glucose concentrations were differently affected during both conditions showing higher levels under H. Despite similar maximal concentrations, the increase of human growth hormone (hGH) was faster during exercise during H than during N[hGHtot after 30 min: 8.6 (SD 11.4) ng.ml-1 (N); 16.2 (SD 11.6) ng.ml-1 (H); P < 0.05]. The variations in plasma [hGH20kD] were closely correlated to those of [hGHtot], but its absolute concentration did not exceed 3% of the [hGHtot]. Plasma IGF I concentration was significantly decreased 24 h after both experimental conditions [N from 319 (SD 71) ng.ml-1 to 228 (SD 72) ng.ml-1, P < 0.05; H from 253 (SD 47) to 200 (SD 47) ng.ml-1, P < 0.01], and was still lower than basal levels 48 h after exercise during H [204 (SD 44) ng.ml-1, P < 0.01]. Linear regression analysis yielded no significant correlation between increase in plasma [hGHtot] or [hGH20kD] during exercise and the plasma IGF I concentration after exercise. It was concluded that the exercise-associated elevated plasma [hGH] did not increase the hepatic IGF I production. From our study it would seem that the high energy demand during and after the long-lasting intensive exercise may have overridden an existing hGH stimulus on plasma IGH I, which was most obvious during hypoxia.

Adult↗
PubMed1995

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.

Adult↗
PubMed1992

Acute administration of bromocriptine abolishes the hyperprolactinemic response induced by submaximal exercise in man.

The effective control of hypophysial prolactin (PRL) secretion with a pharmacological agent is a prerequisite for the investigation of the role of hyperprolactinemia observed during exercise. Using bromocriptine, a potent inhibitor of PRL secretion, this study established the proper experimental conditions whereby any significant increase in plasma PRL level can be prevented and basal circulating levels maintained during physical exercise. On three occasions at weekly intervals, 15 male adults, separated into two groups, exercised on an ergocycle (40 min at 65% VO2max) either 1 or 3 h after ingesting either placebo or 1.25 or 2.50 mg of bromocriptine mesylate (Parlodel; Sandoz Canada Inc., Dorval, Qué.). Under all conditions, the plasma PRL elevation observed during exercise after placebo was prevented by the administration of bromocriptine. Resting plasma PRL levels were maintained when exercise was performed 1 h after bromocriptine ingestion, but were significantly reduced when exercise was performed 3 h after administration of either bromocriptine dosages. Considering the primary and secondary effects observed, 1.25 mg of bromocriptine administered 1 h before exercise provides suitable experimental conditions to investigate the role of the increase in plasma PRL during physical exercise.

Administration, Oral↗
PubMed1992

Blood banking-induced senescent modifications on red blood cells.

In the past few years significant progress has been made in the extension of storage time for red blood cells (RBCs). Albeit this, membrane still undergoes damage during conservation under blood bank conditions, reducing red cell viability following transfusion. Consequently in this study, we evaluated the presence of senescence indices (appearing on RBCs during in vivo aging) on blood bank stored RBCs, more precisely the 4.1a/4.1b ratio and the binding of autologous immunoglobulins. Although not significant, a slight increase (0.995 +/- 0.070 to 1.008 +/- 0.058) was observed in the 4.1a/4.1b ratio during the first three weeks of storage. A rapid and significant (p less than 0.001) increase in the number of cell-bound IgGs (91 +/- 22 to 913 +/- 92), following incubation with purified autologous IgGs, was observed in the first days of storage. Thus, following transfusion, binding of autologous IgGs to stored RBCs could influence post-transfusion viability.

Acids↗
PubMed1991

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.

Amphotericin B↗
PubMed1991

HGH20k species and variability of GH responses to long-duration exercise in male cyclists fed different food supplements.

Exercise studies dealing with hGH have always considered this hormone as a unique molecular entity. We postulated that the well-known variability in blood total hGH response could possibly be explained, at least in part, by concomitant changes in blood hGH20k levels, variant form possibly expressing some of the hGH anti-insulinic properties. Six male trained cyclists were imposed a 2-hr long ergocycle exercise. Food supplements were given prior to and/or during exertion to exacerbate a possible contribution from hGH20k to total hGH variability by modification of substrate availability. Both blood total hGH and hGH20k levels increased with exercise, the largest increases being observed in absence of supplementation. Large variability of responses were observed in both blood total hGH and hGH20k levels, the latter variant contributing minimally to total blood hGH response (4.3 +/- 0.8%), and being closely associated with the main species (r = 0.90; p less than 0.001). It was concluded that variations associated with hGH20k increases observed in response to prolonged exercise cannot explain the large intra-and inter-individual variability measured in blood total hGH response.

Adult↗
PubMed1991

Prolactinotrophic effect of endogenous and exogenous heat loads in human male adults.

Factors associated with heat-induced increase in blood prolactin (PRL) were investigated. Ten male volunteers (23.7 +/- 2.2 yr) were exposed to exogenous heating (head-out immersion) in 41 degrees C water (control 37 degrees C) for 30 min with and without face fanning and cooling. In seven of the subjects, endogenous heating was produced by a 45-min exercise in a warm environment (41 degrees C; control 10 degrees C) with and without selective face fanning. Venous blood was collected before and after each trial; blood hormones were analyzed by radioimmunologic techniques. Heat loading, whether exogenous or endogenous in origin, induced significant increases in blood PRL, beta-endorphin, and vasoactive intestinal peptide (VIP) levels. Blood thyrotropin (TSH) level decreased significantly during water immersion and more significantly with face cooling. From measurement in peripheral blood, the differential beta-endorphin, VIP, and TSH responses to selective face ventilation during exogenous and endogenous heat exposures suggest that blood PRL released in heat derives from secretory stimuli that are independent of these prolactinotropic factors.

Adult↗