Agence francaise de lutte contre le dopage

Saint-Germain-de-Prinçay, France

Agence francaise de lutte contre le dopage

Saint-Germain-de-Prinçay, France

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Collomp K.,University of Orléans | Buisson C.,Agence Francaise de Lutte Contre le Dopage | Lasne F.,Agence Francaise de Lutte Contre le Dopage | Collomp R.,Nice University Hospital Center
Journal of Steroid Biochemistry and Molecular Biology | Year: 2015

The dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S) concentrations during acute and chronic exercise (training) have been investigated only fairly recently. DHEA is generally preferred to DHEA-S for exploring the acute exercise repercussions in laboratory or field tests because of its shorter elimination half-life. Conversely, DHEA-S is preferred to estimate chronic adaptations. Both can be measured noninvasively in saliva, and it is therefore possible to follow these hormone responses in elite athletes during competitive events and in healthy and pathological populations, without imposing additional stress. Indeed, the correlation between saliva and serum concentrations is high for steroid hormones, both at rest and during exercise. In this review, we will first summarize the current knowledge on the DHEA/DHEA-S responses to exercise and examine the potential modulating factors: exercise intensity, gender, age, and training. We will then discuss the ergogenic effects that athletes expect from the exogenous administration of DHEA and the antidoping methods of analysis currently used to detect this abuse. © 2014 Elsevier Ltd. All rights reserved.

PubMed | Agence Francaise de Lutte contre le Dopage, French Institute of Health and Medical Research, French National Institute for Agricultural Research and Jean Monnet University
Type: Journal Article | Journal: Cellular and molecular life sciences : CMLS | Year: 2015

Skeletal muscle is a metabolically active tissue and the major body protein reservoir. Drop in ambient oxygen pressure likely results in a decrease in muscle cells oxygenation, reactive oxygen species (ROS) overproduction and stabilization of the oxygen-sensitive hypoxia-inducible factor (HIF)-1. However, skeletal muscle seems to be quite resistant to hypoxia compared to other organs, probably because it is accustomed to hypoxic episodes during physical exercise. Few studies have observed HIF-1 accumulation in skeletal muscle during ambient hypoxia probably because of its transient stabilization. Nevertheless, skeletal muscle presents adaptations to hypoxia that fit with HIF-1 activation, although the exact contribution of HIF-2, I kappa B kinase and activating transcription factors, all potentially activated by hypoxia, needs to be determined. Metabolic alterations result in the inhibition of fatty acid oxidation, while activation of anaerobic glycolysis is less evident. Hypoxia causes mitochondrial remodeling and enhanced mitophagy that ultimately lead to a decrease in ROS production, and this acclimatization in turn contributes to HIF-1 destabilization. Likewise, hypoxia has structural consequences with muscle fiber atrophy due to mTOR-dependent inhibition of protein synthesis and transient activation of proteolysis. The decrease in muscle fiber area improves oxygen diffusion into muscle cells, while inhibition of protein synthesis, an ATP-consuming process, and reduction in muscle mass decreases energy demand. Amino acids released from muscle cells may also have protective and metabolic effects. Collectively, these results demonstrate that skeletal muscle copes with the energetic challenge imposed by O2 rarefaction via metabolic optimization.

PubMed | Agence Francaise de Lutte contre le Dopage and University Paris - Sud
Type: | Journal: Steroids | Year: 2016

It is generally acknowledged in the sporting world that glucocorticoid (GC) use enhances physical performance. This pharmacological class is therefore banned by the World Anti-Doping Agency (WADA) in in-competition samples after systemic but not local (defined as any route other than oral, intravenous, intramuscular or rectal) administration, which thus allows athletes to use GCs for therapeutic purposes. According to the 2016 WADA list, the urine reporting level for all GCs is set at 30ng/ml to distinguish between the authorized and banned routes of administration. The actual data on the ergogenic effects of GC intake are nevertheless fairly recent, with the first study showing improved physical performance with systemic GC administration dating back only to 2007. Moreover, the studies over the last decade coupling ergogenic and metabolic investigations in humans during and after GC intake have shown discrepant results. Similarly, urine discrimination between banned and authorized GC use remains complex, but it seems likely to be improved thanks to new analytical studies and the inclusion of the authorized GC uses (local routes of administration and out-of-competition samples) in the WADA monitoring program. In this review, we first summarize the current knowledge on the ergogenic and metabolic GC effects in humans during various types of exercise. We then present the antidoping legislation and methods of analysis currently used to detect GC abuse and conclude with some practical considerations and perspectives.

PubMed | University Grenoble Alpes, Grenoble University Hospital Center, Sportiva, Agence Francaise de Lutte contre le Dopage and Ecole Nationale des Sports de Montagne
Type: Journal Article | Journal: PloS one | Year: 2016

Mont Blanc, the summit of Western Europe, is a popular but demanding high-altitude ascent. Drug use is thought to be widespread among climbers attempting this summit, not only to prevent altitude illnesses, but also to boost physical and/or psychological capacities. This practice may be unsafe in this remote alpine environment. However, robust data on medication during the ascent of Mont Blanc are lacking. Individual urine samples from male climbers using urinals in mountain refuges on access routes to Mont Blanc (Goter and Cosmiques mountain huts) were blindly and anonymously collected using a hidden automatic sampler. Urine samples were screened for a wide range of drugs, including diuretics, glucocorticoids, stimulants, hypnotics and phosphodiesterase 5 (PDE-5) inhibitors. Out of 430 samples analyzed from both huts, 35.8% contained at least one drug. Diuretics (22.7%) and hypnotics (12.9%) were the most frequently detected drugs, while glucocorticoids (3.5%) and stimulants (3.1%) were less commonly detected. None of the samples contained PDE-5 inhibitors. Two substances were predominant: the diuretic acetazolamide (20.6%) and the hypnotic zolpidem (8.4%). Thirty three samples were found positive for at least two substances, the most frequent combination being acetazolamide and a hypnotic (2.1%). Based on a novel sampling technique, we demonstrate that about one third of the urine samples collected from a random sample of male climbers contained one or several drugs, suggesting frequent drug use amongst climbers ascending Mont Blanc. Our data suggest that medication primarily aims at mitigating the symptoms of altitude illnesses, rather than enhancing performance. In this hazardous environment, the relatively high prevalence of hypnotics must be highlighted, since these molecules may alter vigilance.

Llouquet J.L.,French Boxing Federation | Crepin N.,Agence francaise de lutte contre le dopage | Lasne F.,Agence francaise de lutte contre le dopage
Drug Testing and Analysis | Year: 2013

Luteinizing hormone (LH) is physiologically produced by the anterior pituitary gland. Male athletes may use pharmaceutical LH for doping since it increases the production of testosterone by testes. This hormone is thus on the World Anti-Doping Agency (WADA) list of substances prohibited for males. Anti-doping laboratories perform the assay of this hormone in urine and report abnormally elevated results. We observed a highly significant prevalence of abnormal results in samples taken after a boxing match. Comparison of the descriptive statistics for 426 LH values observed in boxing and other sports showed significant differences. An experimental study comparing urinary LH levels in 17 boxers before and after a match demonstrated a clear increase after the match. The same observation was made for urinary follicle stimulating hormone (FSH) in all of the eight boxers tested for this other pituitary gonadotropin. These observations have consequences for anti-doping controls, as the reference range for urinary LH levels must take into account the specificities of boxers. They also suggest consequences for the health of boxers. Although to our knowledge such observations have never been described, other pituitary disorders have been reported. Our results deserve further investigation from a medical point of view. © 2013 John Wiley & Sons, Ltd.

Martin L.,Agence Francaise de Lutte contre le Dopage | Chaabo A.,Agence Francaise de Lutte contre le Dopage | Lasne F.,Agence Francaise de Lutte contre le Dopage
Drug Testing and Analysis | Year: 2015

As a synthetic analogue of adrenocorticotropic hormone (ACTH), tetracosactide is prohibited in sport by the World Anti-Doping Agency (WADA). An enzyme-linked immunosorbent assay (ELISA) method is proposed for detection of this drug in plasma. Since its structure corresponds to the 24N-terminal of the 39 amino acids of the natural endogenous peptide ACTH, tetracosactide can be detected with a commercial ELISA kit for ACTH that uses antibodies, the epitopes of which are located in the 1-24 part of ACTH. However, an essential condition for detection specificity is the preliminary total clearance of endogenous ACTH in the plasma samples. This is achieved by a preparative step based on cation-exchange chromatography before ELISA. The method is specific and sensitive (LOD: 30pg/mL) and may be used as a screening analysis in anti-doping control. The pre-analytical conditions are shown to be of the upmost importance and recommendations for blood collection (EDTA tubes), sample transport (4°C) and plasma sample storage (-20°C) are presented. © 2014 John Wiley & Sons, Ltd.

Marijon E.,French Institute of Health and Medical Research | Marijon E.,University of Paris Descartes | Tafflet M.,French Institute of Health and Medical Research | Tafflet M.,University of Paris Descartes | And 17 more authors.
Circulation | Year: 2011

BACKGROUND-: Although such data are available for young competitive athletes, the prevalence, characteristics, and outcome of sports-related sudden death have not been assessed previously in the general population. METHODS AND RESULTS-: A prospective and comprehensive national survey was performed throughout France from 2005 to 2010, involving subjects 10 to 75 years of age. Case detection for sports-related sudden death, including resuscitated cardiac arrest, was undertaken via national ambulance service reporting and Web-based screening of media releases. The overall burden of sports-related sudden death was 4.6 cases per million population per year, with 6% of cases occurring in young competitive athletes. Sensitivity analyses used to address suspected underreporting demonstrated an incidence ranging from 5 to 17 new cases per million population per year. More than 90% of cases occurred in the context of recreational sports. The age of subjects was relatively young (mean±SD 46±15 years), with a predominance of men (95%). Although most cases were witnessed (93%), bystander cardiopulmonary resuscitation was only commenced in 30.7% of cases. Bystander cardiopulmonary resuscitation (odds ratio 3.73, 95% confidence interval 2.19 to 6.39, P<0.0001) and initial use of cardiac defibrillation (odds ratio 3.71, 95% confidence interval 2.07 to 6.64, P<0.0001) were the strongest independent predictors for survival to hospital discharge (15.7%, 95% confidence interval 13.2% to 18.2%). CONCLUSIONS-: Sports-related sudden death in the general population is considerably more common than previously suspected. Most cases are witnessed, yet bystander cardiopulmonary resuscitation was only initiated in one third of cases. Given the often predictable setting of sports-related sudden death and that prompt interventions were significantly associated with improved survival, these data have implications for health services planning. Copyright © 2011 American Heart Association.

Kiss A.,CNRS Institute of Analytical Sciences | Bordes C.,CNRS Institute of Analytical Sciences | Buisson C.,Agence Francaise de Lutte Contre le Dopage | Lasne F.,Agence Francaise de Lutte Contre le Dopage | And 2 more authors.
Analytical and Bioanalytical Chemistry | Year: 2014

Metabonomics has become a very valuable tool and many research fields rely on results coming out from this combination of analytical techniques, chemometric strategies, and biological interpretation. Moreover, the matrices are more and more complex and the implications of the results are often of major importance. In this context, the need for pertinent validation strategies comes naturally. The choice of the appropriate chemometric method remains nevertheless a difficult task due to particularities such as: the number of measured variables, the complexity of the matrix and the purposes of the study. Consequently, this paper presents a detailed metabonomic study on human urine with a special emphasis on the importance of assessing the data's quality. It also describes, step by step, the statistical tools currently used and offers a critical view on some of their limits. In this work, 29 urine samples among which 15 samples obtained from tetrahydrocannabinol (delta-9- tetrahydrocannabinol)-consuming athletes, 5 samples provided by volunteers, and 9 samples obtained from athletes were submitted to untargeted analysis by means of ultra high-pressure liquid chromatography-electrospray ionization-time-of- flight mass spectrometry. Next, the quality of the obtained data was assessed and the results were compared to those found in databases. Then, unsupervised (principal component analysis (PCA)) and supervised (ANOVA/PCA, partial least-square-discriminant analysis (PLS-DA), orthogonal PLS-DA) univariate and multivariate statistical methods were applied. [Figure not available: see fulltext.] © 2013 Springer-Verlag Berlin Heidelberg.

PubMed | Agence Francaise de Lutte contre le Dopage
Type: | Journal: Methods in molecular biology (Clifton, N.J.) | Year: 2015

Nonspecific interactions between blotted proteins and unrelated secondary antibodies generate false positives in immunoblotting techniques. Some procedures have been developed to reduce this adsorption, but they may work in specific applications and be ineffective in others. Double-blotting has been developed to overcome this problem. It consists of interpolating a second blotting step between the usual probings of the blot membrane with the primary antibody and the secondary antibodies. This step, by isolating the primary antibody from the interfering proteins, guarantees the specificity of the probing with the secondary antibody. This method has been developed for the study of erythropoietin in concentrated urine since a strong nonspecific binding of biotinylated secondary antibodies to some urinary proteins is observed using classical immunoblotting protocols. However, its concept makes it usable in other applications that come up against this kind of problem. This method is expected to be especially useful for investigating proteins that are present in minute amounts in complex biological media.

PubMed | University of New Orleans, CNRS Paris Institute of Molecular Chemistry and Agence Francaise de Lutte Contre le Dopage
Type: Journal Article | Journal: Analytical chemistry | Year: 2016

Nonpolar anabolic steroids are doping agents that typically do not provide strong signals by electrospray ionization-mass spectrometry (ESI-MS) owing especially to the low polarity of the functional groups present. We have investigated the addition of anions, in ammonium salt form, to anabolic steroid samples as ionization enhancers and have confirmed that lower instrumental limits of detection (as low as 10 ng/mL for fluoxymesterone-M) are obtained by fluoride anion attachment mass spectrometry, as compared to ESI(+)/(-) or atmospheric pressure photoionization (APPI)(+). Moreover, collision-induced decomposition (CID) spectra of precursor fluoride adducts of the bifunctional steroid reduced pregnenolone (containing two hydroxyl groups) and its d4-analogue provide evidence of regiospecific decompositions after attachment of fluoride anion to a specific hydroxyl group of the steroid. This type of charting of specific CID reaction pathways can offer value to selected reaction monitoring experiments (SRM) as it may result in a gain in selectivity in detection as well as in improvements in quantification.

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