Metabolomic signatures in elite cyclists: differential characterization of a seeming normal endocrine status regarding three serum hormones.

INTRODUCTION: Serum phenotyping of elite cyclists regarding cortisol, IGF1 and testosterone is a way to detect endocrine disruptions possibly explained by exercise overload, non-balanced diet or by doping. This latter disruption-driven approach is supported by fundamental physiology although without any evidence of any metabolic markers. OBJECTIVES: Serum samples were distributed through Low, High or Normal endocrine classes according to hormone concentration. A 1H NMR metabolomic study of 655 serum obtained in the context of the longitudinal medical follow-up of 253 subjects was performed to discriminate the three classes for every endocrine phenotype. METHODS: An original processing algorithm was built which combined a partial-least squares-based orthogonal correction of metabolomic signals and a shrinkage discriminant analysis (SDA) to get satisfying classifications. An extended validation procedure was used to plan in larger size cohorts a minimal size to get a global prediction rate (GPR), i.e. the product of the three class prediction rates, higher than 99.9%. RESULTS: Considering the 200 most SDA-informative variables, a sigmoidal fitting of the GPR gave estimates of a minimal sample size to 929, 2346 and 1408 for cortisol, IGF1 and testosterone, respectively. Analysis of outliers from cortisol and testosterone Normal classes outside the 97.5%-confidence limit of score prediction revealed possibly (i) an inadequate protein intake for outliers or (ii) an intake of dietary ergogenics, glycine or glutamine, which might explain the significant presence of heterogeneous metabolic profiles in a supposedly normal cyclists subgroup. CONCLUSION: In a next validation metabolomics study of a so-sized cohort, anthropological, clinical and dietary metadata should be recorded in priority at the blood collection time to confirm these functional hypotheses.

Quantification of physical activity using the QAPACE Questionnaire: a two stage cluster sample design survey of children and adolescents attending urban school.

BACKGROUND: Quantification of physical activity as energy expenditure is important since youth for the prevention of chronic non communicable diseases in adulthood. It is necessary to quantify physical activity expressed in daily energy expenditure (DEE) in school children and adolescents between 8-16 years, by age, gender and socioeconomic level (SEL) in Bogotá. METHODS: This is a Two Stage Cluster Survey Sample. From a universe of 4700 schools and 760000 students from three existing socioeconomic levels in Bogotá (low, medium and high). The random sample was 20 schools and 1840 students (904 boys and 936 girls). Foreshadowing desertion of participants and inconsistency in the questionnaire responses, the sample size was increased. Thus, 6 individuals of each gender for each of the nine age groups were selected, resulting in a total sample of 2160 individuals. Selected students filled the QAPACE questionnaire under supervision. The data was analyzed comparing means with multivariate general linear model. Fixed factors used were: gender (boys and girls), age (8 to 16 years old) and tri-strata SEL (low, medium and high); as independent variables were assessed: height, weight, leisure time, expressed in hours/day and dependent variable: daily energy expenditure DEE (kJ.kg-1.day-1): during leisure time (DEE-LT), during school time (DEE-ST), during vacation time (DEE-VT), and total mean DEE per year (DEEm-TY) RESULTS: Differences in DEE by gender, in boys, LT and all DEE, with the SEL all variables were significant; but age-SEL was only significant in DEE-VT. In girls, with the SEL all variables were significant. The post hoc multiple comparisons tests were significant with age using Fisher's Least Significant Difference (LSD) test in all variables. For both genders and for all SELs the values in girls had the higher value except SEL high (5-6) The boys have higher values in DEE-LT, DEE-ST, DEE-VT; except in DEEm-TY in SEL (5-6) In SEL (5-6) all DEEs for both genders are highest. For SEL (3-4) all DEEs are lowest. CONCLUSIONS: Children and adolescents in Bogotá have less DEE than at other latitudes. Girls have more free time but lower energy expenditure in their different activities. The socioeconomic level has influence in DEE.

Sports-related sudden death in the general population.

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.

A physical activity questionnaire: reproducibility and validity.

This study evaluates the Quantification de L'Activite Physique en Altitude chez les Enfants (QAPACE) supervised self-administered questionnaire reproducibility and validity on the estimation of the mean daily energy expenditure (DEE) on Bogotá's schoolchildren. The comprehension was assessed on 324 students, whereas the reproducibility was studied on a different random sample of 162 who were exposed twice to it. Reproducibility was assessed using both the Bland-Altman plot and the intra-class correlation coefficient (ICC). The validity was studied in a sample of 18 girls and 18 boys randomly selected, which completed the test - re-test study. The DEE derived from the questionnaire was compared with the laboratory measurement results of the peak oxygen uptake (Peak VO2) from ergo-spirometry and Leger Test. The reproducibility ICC was 0.96 (95% C.I. 0.95-0.97); by age categories 8-10, 0.94 (0.89-0. 97); 11-13, 0.98 (0.96- 0.99); 14-16, 0.95 (0.91-0.98). The ICC between mean TEE as estimated by the questionnaire and the direct and indirect Peak VO2 was 0.76 (0.66) (p<0.01); by age categories, 8-10, 11-13, and 14-16 were 0.89 (0.87), 0.76 (0.78) and 0.88 (0.80) respectively. The QAPACE questionnaire is reproducible and valid for estimating PA and showed a high correlation with the Peak VO2 uptake. Key pointsThe presence of a supervisor, the limited size of the group with the possibility of answering to their questions could explain the high reproducibility for this questionnaire.No study in the literature had directly addressed the issue of estimating a yearly average PA including school and vacation period.A two step procedure, in the population of schoolchildren of Bogotá, gives confidence in the use of the QAPACE questionnaire in a large epidemiological survey in related populations.

Exercise limitation in trained heart and kidney transplant recipients: central and peripheral limitations.

BACKGROUND: To evaluate the role of central and peripheral contributions to exercise limitation after transplantation, we compared, during exercise, 2 groups of very well-trained heart transplants recipients (HTRs) and kidney transplant recipients (KTRs) with a group of control subjects (CSs), matched for physical level. METHODS: Nineteen male subjects, 7 HTRs, 6 KTRs and 6 CSs, participated in the study. All transplant patients were in sinus rhythm and were matched for immunosuppressive therapy, none of whom had therapy with chronotropic effects. Exercise capacities were evaluated using a symptom-limited treadmill test. Oxygen consumption (VO2) and heart rate (HR) were measured continuously. Heart rate reserve (HRR) was defined as peak HR minus resting HR; resting HR was the stabilized HR measured in the supine position before the treadmill test. RESULTS: Functional capacities were evaluated for all HTRs, KTRs and CSs, according to maximal VO2 (41.5 +/- 4.0, 52.0 +/- 8.7 and 50.6 +/- 9.0 ml/kg per min, respectively), maximal treadmill speed (9.9 +/- 1.2, 12.7 +/- 1.9 and 15.5 +/- 1.5 km/h) and HRR (65 +/- 17, 101 +/- 12 and 110 +/- 11 beats per minute [bpm]), which were significantly lower in the HTR group (p < 0.05). Regardless of type of organ transplant, both HTR and KTR patients had a similar VO2/treadmill speed relationship, significantly higher than in the CS group. HRR correlated with maximal VO2 for HTRs (r = 0.72, p < 0.05). CONCLUSIONS: Despite regular training, the decreased mechanical efficiency reflected by an increased VO2/treadmill speed relationship suggests a peripheral limitation in both heart and kidney transplant patients. Furthermore, exercise limitations in HTRs likely arose from both central and peripheral factors, in view of their specific HRR reduction. These factors probably contributed to the decreased speed and VO2 observed in the HTR group.

[The fight against doping: today and tomorrow]. / La lutte contre le dopage: maintenant et demain.

Since Antiquity, sport persons have used doping methods to improve their performance. The methods used today are increasingly specific and professional As a corrolary, doping is becoming extremely difficult to detect: because many prohibited drugs are rapidly metabolized (short half life); it is often impossible to distinguish between the natural and recombinant hormone products; several prohibited substances are not screened for; therapeutic use authorization (TUA)--a recent recommendation from the World antidoping agency (WADA)--and advances in gene therapy are giving cheaters new possibilities. It is necessary to promote a new approach to doping detection by determining potential specific links between changes in human biological profiles (proteom, transcriptom, metabonom), and the use of a given drug. Developments in nanotechnology, and notably" labs on a chip" should prove useful in this respect.

Pyruvate shuttle in muscle cells: high-affinity pyruvate transport sites insensitive to trans-lactate efflux.

The specificity of the transport mechanisms for pyruvate and lactate and their sensitivity to inhibitors were studied in L6 skeletal muscle cells. Trans- and cis-lactate effects on pyruvate transport kinetic parameters were examined. Pyruvate and lactate were transported by a multisite carrier system, i.e., by two families of sites, one with low affinity and high capacity (type I sites) and the other with high affinity and low capacity (type II). The multisite character of transport kinetics was not modified by either hydroxycinnamic acid (CIN) or p-chloromercuribenzylsulfonic acid (PCMBS), which exert different types of inhibition. The transport efficiency (TE) ratios of maximal velocity to the trans-activation dissociation constant (Kt) showed that lactate and pyruvate were preferentially transported by types I and II sites, respectively. The cis-lactate effect was observed with high Ki values for both sites. The trans-lactate effect on pyruvate transport occurred only on type I sites and exhibited an asymmetric interaction pattern (Kt of inward lactate > Kt of outward lactate). The inability of lactate to trans-stimulate type II sites suggests that intracellular lactate cannot recruit these sites. The high-affinity type II sites act as a specific pyruvate shuttle and constitute an essential relay for the intracellular lactate shuttle.

Recovery of slow skeletal muscle after injury in the senescent rat.

We studied the contractile, histological and biochemical characteristics of regenerating slow (soleus) muscles of aged rats and the effect of IGF-1 treatment on these parameters. Regenerating soleus muscles were studied 21 days after myotoxic injury. In senescent rats (24 month old), the in situ isometric maximal tetanic force (P0), resistance to fatigue (T20%P0) and shortening speed with an afterload of 20%P0 (SS20%P0) were lower (p<0.05) in regenerating soleus muscles as compared to uninjured controlateral soleus muscles. Moreover, the expression of type 1 myosin heavy chain (MHC-1) was decreased by injury in the soleus muscles of senescent rats (p<0.05). Furthermore, a single injection of IGF-1 (3 microg) into the soleus of senescent rats only slightly increased the level of sarcoplasmic reticulum type 2 Ca(2+)-ATPase in regenerating soleus muscles (p<0.01). Contrary to senescent animals, regenerating soleus of adult rats (10 month old) did not present significantly lower P0 and MHC-1 expression than uninjured controlateral muscles (p>0.05). In conclusion, the regeneration of a slow muscle is more uncompleted 3 weeks after myotoxic injury in senescent rats than in adult rats. It cannot be made more effective by a single injection of IGF-1 into the senescent slow muscle.