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The relationship between inflammatory markers and bone turnover in adults is well known, whilst a negative association between cardiorespiratory fitness (CRF) and inflammatory markers has also been described. Hence, we tested whether the association between CRF and bone turnover markers is mediated by inflammatory markers in adults with metabolic syndrome. A total of 81 adults (58.5±5.0 yrs, 62.7% women) were included in the analysis. CRF was measured by the six-minute walking test. Serum interleukine (IL)-1β, IL-6, IL-10, tumor necrosis factor alpha, high-sensitivity c-reactive protein (hsCRP) and vascular endothelial growth factor, collagen type I cross-linked C-telopeptide, procollagen type I N-terminal propeptide (P1NP) and total osteocalcin were assessed using a sensitive ELISA kit. Body composition was assessed by dual-energy x-ray absorptiometry. Partial correlation was used to test the relationship between CRF, inflammatory markers and bone turnover markers, controlling for sex, lean mass and fat mass. Boot-strapped mediation procedures were performed and indirect effects with confidence intervals not including zero were interpreted as statistically significant. CRF was positively correlated with P1NP levels (r=0.228, p=0.044) and osteocalcin levels (r=0.296, p=0.009). Furthermore, CRF was positively correlated with IL-1β levels (r=0.340, p=0.002) and negatively correlated with hsCRP levels (r=-0.335, p=0.003), whereas IL-1β levels were positively correlated with P1NP levels (r=0.245, p=0.030) and hsCRP levels were negatively correlated with P1NP levels (r=-0.319, p=0.004). Finally, the association between CRF and P1NP levels was totally mediated by hsCRP (PM=39.9). Therefore, CRF benefits on bone formation could be dependent on hsCRP concentrations in this population., Heart and Diseases Foundation (Fondation 234 Coeur et Artères) 59200 Loos, France

International audience; The rise in oxygen consumption during the transition from rest to exercise is faster in those who are endurance-trained than those who have sedentary lifestyles, partly due to a more efficient cardiac response. However, data regarding this acute cardiac response in trained individuals are limited to heart rate (HR), stroke volume and cardiac output. Considering this, we compared cardiac kinetics, including left ventricular (LV) strains and twist/untwist mechanics, between endurance-trained cyclists and their sedentary counterparts. Twenty young, male, trained cyclists and 23 untrained participants aged 18-25 years performed five similar constant workload exercises on a cyclo-ergometer (target HR: 130 bpm). During each session, LV myocardial diastolic and systolic linear strains, as well as torsional mechanics, were assessed using speckle-tracking echocardiography. Cardiac function was evaluated every 15s during the first minute and every 30s thereafter, until 240s. Stroke volume increased during the first 30-45s in both groups, but to a significantly greater extent in trained cyclists (31% vs 24%). Systolic parameters were similar in both groups. Transmitral peak filling velocity and peak filling rate responded faster to exercise and with greater amplitude in trained cyclists. Left ventricular filling pressure was lower in the former, while LV relaxation was greater, but only at the base of the left ventricle. Basal rotation and peak untwisting rate responded faster and to a greater extent in the cyclists. This study provides new mechanical insights into the key role of LV untwisting in the more efficient acute cardiac response of endurance-trained athletes at onset of exercise.

International audience; Background: Left ventricular (LV) remodeling, characterized by increased LV hypertrophy and depressed function, is observed in strength-trained athletes who use anabolic-androgenic steroids (AAS). Previous studies reported an increase in cardiac fibrosis in these athletes, which could promote intraventricular dyssynchrony. In this context, this study evaluated LV dyssynchrony in strength-trained athletes using AA; hypothesizing that the use of AAS leads to an increase in LV dyssynchrony with an increase in post-systolic shortening.Methods: Forty-four participants (aged 20-40 years) were divided into three age-matched groups: strength-trained athletes using AAS (users, n=14) and those who were not (non-users, n=15), and healthy sedentary men (controls, n=15),. After completing a survey, each participant was assessed with 2D-strain echocardiography. Left ventricular dyssynchrony was quantified using the standard deviation of the time to peak for longitudinal strains (SD), the longitudinal strain delay index (LSDI) and the segmental post-systolic index (PSI).Results: Users exhibited a greater LV mass index and higher systolic and diastolic functions than both controls and non-users. The decrease in LV strains in users was predominantly observed at the interventricular segments. The SD, LSDI and PSI, calculated on the basal inferoseptal, basal anteroseptal and basal inferolateral segments, were higher in users.Conclusion: The results strongly support that the specific LV remodeling observed in young AAS users was associated with an increase in LV dyssynchrony. The correlations with ejection fraction suggested that wasted energy, due to post-systolic shortenings, contributed in part to the decrease in LV function in strength-trained athletes using AAS.

To evaluate the effectiveness of vitamin DMice were fed a high fat and sucrose diet for 10 weeks. Afterward, diet was maintained for 15 more weeks and two groups were formed, with and without cholecalciferol supplementation. A control group was fed with normal chow. Glucose homeostasis and cardiac function were assessed at baseline and at the 10th and 24th weeks. Animals were killed at the 10th and 25th weeks for plasma and cardiac sample analysis. Cardiac lipid profile was characterized by LC-MS/MS.After 10 weeks of diet, mice exhibited pre-diabetes, mild left ventricle hypertrophy, and impaired longitudinal strain, but preserved myocardial circumferential as well as global diastolic and systolic cardiac function. After 15 more weeks of diet, animals presented with well-established type 2 diabetes, pathological cardiac hypertrophy, and impaired regional myocardial function. Cholecalciferol supplementation had no effect on glucose homeostasis but improved cardiac remodeling and regional myocardial function. After 25 weeks, non-supplemented mice exhibited increased myocardial levels of ceramides and diacylglycerol, both of which were normalized by vitamin DThis work brought to light the beneficial effects of cholecalciferol supplementation, in secondary prevention, on cardiac remodeling and function in a mouse model of diet-induced type 2 diabetes. Those cardioprotective effects may be, at least in part, attributed to the modulation of myocardial levels of lipotoxic species by vitamin D.

Despite potential severe cardiac side effects, anabolic androgenic steroids (AAS) are increasingly used by strength athletes. However, previous echocardiographic studies focused on the left ventricular (LV) strains but did not assess LV twist and untwist mechanics. Moreover, left atrial (LA) function has been often neglected, and its stiffness, an important determinant of LA reservoir function, has never been challenged. The aim of this study was to investigate the effects of AAS on LA and LV morphologies and functions in strength athletes.Fifty subjects including 20 strength-trained young athletes age 32.0 ± 8.5 yr with a mean duration of AAS use of 4.7 ± 1.8 yr (users), 15 athletes with no history of AAS use (nonusers) and 15 sedentary controls underwent speckle tracking echocardiography to assess LA and LV morphology and function.Users showed higher LA reservoir dysfunction than nonusers (33.7% ± 10.9% vs 44.9% ± 9.9% respectively, P = 0.004) and higher LA stiffness (0.13 ± 0.05 vs 0.19 ± 0.08 A.U., respectively; P = 0.02), higher LV mass index and lower global and regional LV diastolic and systolic dysfunction (global longitudinal strain: -15.5% ± 3.2% vs -18.9% ± 1.8% respectively; P = 0.003), with a drop of LV twist-untwist mechanics (untwisting velocity: 61.5°·s-1 ± 20.2°·s-1 vs 73.7°·s-1 ± 16.1°·s-1 respectively, P = 0.04). There were significant correlations between LV mass and LV apical rotation (P = 0.003, r = 0.44) and diastolic longitudinal strain rate (P = 0.015, r = 0.33).Our results showing significant LA and LV remodeling and dysfunctions in young AAS using athletes are alarming. Screening echocardiography based on speckle tracking echocardiography parameters for early diagnosis, as well as a stronger awareness in athletes and in physicians are warranted in this context.

International audience; Purpose To evaluate the effectiveness of vitamin D-3 supplementation, in secondary prevention, on cardiac remodeling and function, as well as lipid profile, in a mouse model of diet-induced type 2 diabetes. Methods Mice were fed a high fat and sucrose diet for 10 weeks. Afterward, diet was maintained for 15 more weeks and two groups were formed, with and without cholecalciferol supplementation. A control group was fed with normal chow. Glucose homeostasis and cardiac function were assessed at baseline and at the 10th and 24th weeks. Animals were killed at the 10th and 25th weeks for plasma and cardiac sample analysis. Cardiac lipid profile was characterized by LC-MS/MS. Results After 10 weeks of diet, mice exhibited pre-diabetes, mild left ventricle hypertrophy, and impaired longitudinal strain, but preserved myocardial circumferential as well as global diastolic and systolic cardiac function. After 15 more weeks of diet, animals presented with well-established type 2 diabetes, pathological cardiac hypertrophy, and impaired regional myocardial function. Cholecalciferol supplementation had no effect on glucose homeostasis but improved cardiac remodeling and regional myocardial function. After 25 weeks, non-supplemented mice exhibited increased myocardial levels of ceramides and diacylglycerol, both of which were normalized by vitamin D-3 supplementation. Conclusion This work brought to light the beneficial effects of cholecalciferol supplementation, in secondary prevention, on cardiac remodeling and function in a mouse model of diet-induced type 2 diabetes. Those cardioprotective effects may be, at least in part, attributed to the modulation of myocardial levels of lipotoxic species by vitamin D.

International audience; Purpose Physical exercise (PE) combined with nutritional approaches has beneficial effects that are widely advocated to improve metabolic health. Here we used voluntary PE together with vitamin D (VD) supplementation, which has already shown beneficial effects in primary and tertiary prevention in obese mice models, to study their combined additive effects on body weight management, glucose homeostasis, metabolic inflammation, and liver steatosis as key markers of metabolic health. Methods Ten-week-old male C57BL/6J mice were fed a high-fat/sucrose (HFS) diet for 10 wk, then assigned to a 15-wk intervention period with PE, VD supplementation, or both PE and VD supplementation. Morphological, histological, and molecular phenotype data were characterized. Results The HFS-induced increases in body mass, adiposity, and adipocyte hypertrophy were improved by PE but not by VD supplementation. The HFS-induced inflammation (highlighted by chemokines mRNA levels) in inguinal adipose tissue was decreased by PE and/or VD supplementation. Furthermore, the intervention combining PE and VD showed additive effects on restoring insulin sensitivity and improving hepatic steatosis, as demonstrated through a normalization of size and number of hepatic lipid droplets and triglyceride content and a significant molecular-level decrease in the expression of genes coding for key enzymes in hepatic de novo lipogenesis. Conclusions Taken together, our data show beneficial effects of combining PE and VD supplementation on obesity-associated comorbidities such as insulin resistance and hepatic disease in mice. This combined exercise-nutritional support strategy could prove valuable in obesity management programs.

Objectives: This study was performed to evaluate the long-term maintenance of nutritional changes promoted during an intensive initial intervention to induce body weight loss. The ability of these changes to predict long-term health outcomes was also examined. Methods: Nutritional variables, body composition, and metabolic markers collected in the RESOLVE project were analyzed before and after a 3-week intensive diet&ndash, exercise intervention (Phase 1), and during a subsequent supervision under free living conditions, of 12 months (Phase 2). Results: As expected, the macronutrient composition of the diet was modified to promote a negative energy balance during Phase 1. The decrease in carbohydrates imposed during this phase was maintained during Phase 2 whereas the increase in protein intake returned to baseline values at the end of the program. Dietary fiber intake was almost doubled during Phase 1 and remained significantly greater than baseline values throughout Phase 2. Moreover, fiber intake was the only nutritional variable that systematically and significantly predicted variations of health outcomes in the study. Conclusion: The adequacy of dietary fiber intake should be a matter of primary consideration in diet-based weight reduction programs.

International audience; The beneficial effect of vitamin D (VD) supplementation on body weight gain limitation and inflammation has been highlighted in primary prevention mice models, but the long-term effect of VD supplementation in tertiary prevention has never been reported in obesity models. The curative effect of VD supplementation on obesity and associated disorders was evaluated in high-fat- and high-sucrose (HFS)-fed mice. Morphological, histological, and molecular phenotype were characterized. The increased body mass and adiposity caused by HFS diet as well as fat cell hypertrophy and glucose homeostasis were not improved by VD supplementation. However, VD supplementation led to a decrease of HFS-induced inflammation in inguinal adipose tissue, characterized by a decreased expression of chemokine mRNA levels. Moreover, a protective effect of VD on HFS-induced hepatic steatosis was highlighted by a decrease of lipid droplets and a reduction of triglyceride accumulation in the liver. This result was associated with a significant decrease of gene expression coding for key enzymes involved in hepatic de novo lipogenesis and fatty acid oxidation. Altogether, our results show that VD supplementation could be of interest to blunt the adipose tissue inflammation and hepatic steatosis and could represent an interesting nutritional strategy to fight obesity-associated comorbidities.

Introduction et but de l’etude D’apres l’OMS, l’obesite touche environ 650 millions d’adultes en 2016. Des changements de comportements alimentaires et de modes de vie sont a l’origine de l’emergence de cette pathologie. Elle est definie par une accumulation excessive de tissu adipeux. Recemment, il a ete montre qu’une deficience en micronutriments, notamment en vitamine D (vitD), et un etat inflammatoire chronique etaient retrouves chez les personnes obeses. De plus, nous avons recemment montre qu’une supplementation en vitD limite a la fois la prise de poids et l’inflammation mediees par une alimentation riche en graisse chez la souris. Cependant, l’effet d’une supplementation en vitD en « prevention tertiaire » dans un modele experimental d’obesite n’a encore jamais ete rapporte. Materiel et methodes Des souris C57BL/6 J (n = 80) ont ete soumises a un regime High Fat/Sucrose (HFS) durant 10 semaines afin d’obtenir un phenotype obese. Ensuite, les souris ont ete supplementees en vitD durant 15 semaines. Un suivi des parametres morphologiques et biologiques a ete realise tout au long de l’etude. A la fin du protocole, les differents tissus adipeux et le foie ont ete collectes et des analyses geniques et histologiques ont ete realisees. Resultats et analyse statistique Le regime HFS a entraine une augmentation significative du poids corporel (+60 %) et de la masse de tissus adipeux (perirenal + epididymal, inguinal+ sous-cutane), ainsi qu’une hypertrophie adipocytaire, sans effet correctif de la supplementation en vitD. L’insulino-resistance retrouvee chez les souris HFS n’etait pas amelioree par la vitD. En revanche, l’augmentation de l’inflammation (MCP-1, CCL5) au sein du tissu adipeux inguinal (TAing) retrouvee chez les souris HFS etait significativement diminuee lorsque les souris etaient supplementees en vitD. Enfin, l’analyse de coupes histologiques de foie a permis de mettre en evidence une diminution significative du nombre de gouttelettes lipidiques, suggerant une moindre infiltration lipidique par la supplementation en vitD. Une quantification des triglycerides dans le foie a confirme cette diminution de l’infiltration lipidique. Ce resultat est egalement accompagne d’un effet significatif de la vitD sur la lipogenese au niveau du foie, avec une baisse d’expression des genes cles, la fatty acid synthase (FAS) et l’acetyl-CoA carboxylase (ACC) diminuees de 30 et 35 % respectivement par rapport aux souris HFS. Conclusion Nos resultats montrent que la supplementation en vitD seule n’est pas suffisante pour favoriser la perte de poids et retablir un profil insulino-sensible chez les individus obeses. Neanmoins, la vitD ameliore le statut inflammatoire adipocytaire et permet de diminuer l’infiltration lipidique hepatique signe de steatose hepatique. Afin de potentialiser les effets de la vitD, il serait interessant d’envisager une intervention associant l’exercice physique afin d’agir egalement sur la prise de poids et le developpement du tissu adipeux. Des etudes sont actuellement en cours dans notre laboratoire.

IntroductionStress and obesity are two public health issues. The relationship between obesity and stress is biological through the actions of stress on the major hormones that regulate appetite (leptin and ghrelin). Many spa resorts in France specialise in the treatment of obesity, but no thermal spa currently proposes a specific programme to manage stress in obesity. The ObesiStress protocol has been designed to offer a new residential stress management programme. This thermal spa treatment of obesity implements stress management strategies as suggested by international recommendations.Methods and analysis140 overweight or obese participants with a Body Mass Index of >25 kg/m2 and aged over 18 years will be recruited. Participants will be randomised into two groups: a control group of usual practice (restrictive diet, physical activity and thermal spa treatment) and an intervention group with stress management in addition to the usual practice. In the present protocol, parameters will be measured on five occasions (at inclusion, at the beginning of the spa (day 0), at the end of the spa (day 21), and at 6 and 12 months). The study will assess the participants’ heart rate variability, cardiac remodelling and function, electrodermal activity, blood markers, anthropometric profile, body composition, psychology and quality of life via the use of questionnaires and bone parameters.Ethics and disseminationThe ObesiStress protocol complies with the ethics guidelines for Clinical Research and has been approved by the ethics committee (CPP Sud-Est VI, Clermont-Ferrand - ANSM: 2016-A01774-47). This study aimed to highlight the efficacy of a 21-day thermal spa residential programme of stress management in obesity through objective measurements of well-being and cardiovascular morbidity. Results will be disseminated during several research conferences and articles published in peer-reviewed journals.Trial registration numberNCT03578757.

PURPOSE At the onset of physical exercise, oxygen (O2) transport adapts to meet the working muscle O2 demands. Cardiac output abruptly increases through the concomitant changes of HR and stroke volume (SV), which is conditioned by the left ventricular (LV) function. The purpose of this study was to investigate the contribution of many LV diastolic and systolic function parameters, including twist-untwist mechanics, to SV adaptation during the first minutes after exercise onset. METHODS Diastolic and systolic myocardial strains and twist were monitored by two-dimensional speckle-tracking echocardiography with high temporal resolution in 28 young men (mean age, 23 ± 4 yr) who performed five similar constant work-load exercises on a cycloergometer (target HR: 125 bpm). Two-dimensional cine-loops were recorded every 15 s during the first minute of exercise, and then every 30 s for the next 3 min. RESULTS During the first 60 s of exercise, SV (from 104 ± 15 mL to 126 ± 21 mL, P < 0.001) increased concomitantly with LV strain and strain rates. Early filling was the main SV determinant during this phase, probably linked to the increase of venous return (at the very beginning of exercise), LV relaxation (from 1.5 ± 0.3 s to 2.5 ± 0.4 s, P < 0.001) and untwisting (from -78 ± 34°·s to -165 ± 61°·s, P < 0.001). After the first minute, SV remained constant, whereas LV untwisting continued to increase (from -165 ± 61°·s to -187 ± 60°·s, P < 0.001) and the other systolic and diastolic parameters reached a plateau. CONCLUSIONS This study gives new mechanical insights into LV kinetics to address the challenge of SV response at the onset of exercise.

Aims: The aim of the investigation was to evaluate layer-specific right ventricular (RV) deformation in normotensive and hypertensive subjects with type 2 diabetes mellitus (DM). Methods: This cross-sectional study included 129 subjects (40 controls, 42 normotensive DM and 47 hypertensive DM patients) who underwent complete two-dimensional echocardiographic examination (2DE) including multilayer strain analysis. Results: 2DE RV global and free wall longitudinal strains were reduced in normotensive and hypertensive DM subjects than in controls. RV global longitudinal layer-specific strains (endo-, mid- and epicardial) were lower in normotensive and hypertensive DM patients than in controls. On the other side, layer-specific strains of RV free wall were lower in hypertensive DM patients than in controls, without significant difference between controls and normotensive DM subjects. Parameters of DM control (fasting glucose and glycosylated hemoglobin) were associated with 2DE RV global longitudinal endo- and mid-myocardial layer strain. Conclusions: Diabetes and hypertension significantly influence RV mechanics assessed by 2DE conventional and 2DE multilayer strain. Hypertension has an additive unfavorable influence on RV deformation in diabetic patients. Laboratory parameters of diabetic control were associated with RV structure, diastolic function and mechanics assessed with complex 2DE strain analysis.

Discrepancies are present in the literature on resting myocardial mechanics in patients with uncomplicated type 2 diabetes mellitus (T2DM). Data are noticeably sparse regarding circumferential function and torsional mechanics. Resting deformation imaging may not be sensitive enough to detect subtle dysfunctions. The aim of this study was thus to comprehensively evaluate myocardial mechanics in patients with T2DM at rest and to investigate whether dobutamine stress echocardiography could unmask functional alterations that would remain otherwise subtle at rest.Forty-four patients with T2DM and 35 healthy control subjects of similar age and sex were prospectively recruited. After conventional echocardiography, myocardial mechanics was evaluated at rest and during low-dose dobutamine stress echocardiography (target heart rate, 110 beats/min).Patients with T2DM presented with altered global diastolic function but preserved systolic function. Deformation imaging indexes were similar between groups at rest, but significant differences were noticed under dobutamine infusion for longitudinal strain (-21.2 ± 2.4% vs -24.2 ± 2.5%, P .001), circumferential strain (apex, -32.3 ± 5.3% vs -36.3 ± 5.3%, P = .002; papillary muscle, -25.6 ± 3.2% vs -28.0 ± 3.6%, P = .001; base, -23.2 ± 3.6% vs -25.3 ± 3.8%, P = .03), apical (11.2 ± 4.4° vs 14.1 ± 6.3°, P = .020) and basal (-12.2 ± 3.3° vs -14.3 ± 3.9°, P = .021) rotation, and twist (21.9 ± 5.9° vs 26.8 ± 8.3°, P = .007). Multivariate analysis identified epicardial fat, dyslipidemia, and fasting glycaemia as significant contributors to the changes from rest to dobutamine.These findings demonstrate the usefulness of dobutamine stress echocardiography in establishing impairments in myocardial mechanics in patients with uncomplicated T2DM. Systemic metabolic disturbances and epicardial fat act as the main contributors to the blunted response to dobutamine stress in these patients.

Summary Background Detailed analysis of layer-specific mechanical changes in patients with type 2 diabetes mellitus (DM) might improve insight into left ventricular (LV) remodelling and diabetic cardiomyopathy. Aim We sought to investigate layer-specific LV deformation in patients with DM, with and without hypertension. Methods This cross-sectional study included 146 subjects (44 controls; 48 patients with DM; 54 patients with DM and hypertension) who underwent complete examination by two-dimensional echocardiography (2DE), including multilayer strain analysis. Results 2DE LV longitudinal and circumferential strains deteriorated progressively and significantly from controls, through patients with DM, to patients with DM and hypertension. 2DE radial strain was lower in patients with DM and hypertension than in controls. 2DE longitudinal and circumferential mid-myocardial and epicardial layer strains decreased progressively from controls to patients with DM and hypertension, whereas endocardial layer strain was lower in patients with DM and patients with DM and hypertension than in controls. Variables of DM control (fasting glucose and glycated haemoglobin) were associated with 2DE LV longitudinal and circumferential layer-specific strains, independent of age, body mass index, blood pressure, LV diastolic function and hypertrophy in patients with DM. Conclusion DM and hypertension significantly affect LV deformation assessed by 2DE traditional strain and 2DE multilayer strain. Hypertension showed an additional negative effect on LV deformation in patients with DM. Fasting glucose and glycated haemoglobin were associated with LV mechanics evaluated by comprehensive 2DE strain analysis, independent of LV structure and diastolic function.

Olive oil vascular benefits have been attributed to hydroxytyrosol (HT). However, HT biological actions are still debated because of its high metabolisation into glucuronides (GC). The aim of this study was to test HT and GC vasculoprotective effects on aorta rings from male Wistar rats. Vasorelaxant dose-responses to acetylcholine (ACh) or sodium nitroprusside (SNP) were realized in presence/absence of tert-butylhydroperoxide (t-BHP) (30 min, 500 μM). To prove this antioxidative effect, DHE staining was realized on phenol-treated aortas in oxidative stress conditions. Implication of bilitranslocase, a phenol transporter, and β-glucuronidase, implicated in deconjugation, were assessed using phenylmethanesulfonyl fluoride (PMSF, 100 μM, 20 min) and saccharolactone (SAL, 300 μM, 60 min), respectively. In addition, β-glucuronidase protein expression was assessed by western blot after using the same experimental procedures. In presence of oxidative stress, HT and GC enhanced endothelium-dependent and -independent relaxation to ACh and SNP compared to t-BHP-treated aortas. This effect was associated with a significant reduction in DHE staining for phenol-treated aortas compared to t-BHP-treated aortas. However, this protective effect was lost for GC when a washing step was introduced between phenols incubation and t-BHP stress. Bilitranslocase inhibition with PMSF reduced significantly HT but not GC effect on the vascular function upon stress induction. Moreover, GC protective effect in oxidative stress conditions was reduced by pre-incubation of aorta rings with SAL and was not associated with a reduction in β-glucuronidase protein expression. Finally, only HT was detected by high-pressure liquid chromatography in aorta rings incubated with GC and t-BHP. These results suggest that in conditions of oxidative stress, GC has to be deconjugated into HT that is transported through the cell membrane by bilitranslocase to produce its protective effect on vascular function.

With an aging population and the increasing prevalence of heart failure with preserved ejection fraction, developing strategies to prevent diastolic dysfunction is crucial. Regular endurance training has been suggested to be one such strategy. However, the underlying mechanisms of training, including the effect on left ventricular (LV) untwist, which promotes LV filling, are unclear and studies exploring the heart during exercise in the aging heart are lacking. Cardiopulmonary exercise testing with speckle tracking echocardiography was realized in male subjects: 16 young athletes (YA), 19 young controls (YC), 22 middle-aged athletes (MA) with a lifelong history of endurance training, and 20 middle-aged controls (MC). During exercise, the early filling was lower in MC compared to YC, whereas it was preserved between YA and MA. At exercise, peak untwisting rate/peak twist ratio and the percentage of untwist during isovolumic relaxation time were decreased in senior groups but higher in YA and MA compared to age-matched controls. Early diastolic filling reserve correlated with untwisting rate/peak twist reserve in YA and MA (R 2 = 0.22, p

Controversy exists on whether endothelial function is enhanced in athletes. We sought to systematically review the literature and determine whether endothelial function, as assessed by flow-mediated dilation (FMD), is greater in athletes across all ages relative to that in their age-matched counterparts.We conducted a systematic search on MEDLINE, Cochrane, Scopus, and Web of Science since their inceptions until July 2013 for articles evaluating FMD in athletes. A meta-analysis was performed to compare the standardized mean difference (SMD) in FMD of the brachial artery between athletes and age-matched control subjects. Subgroup analyses and meta-regression were used to identify sources of heterogeneity.Twenty-one articles were included in this analysis, comprising 530 athletes (452 endurance trained, 49 strength trained, and 29 endurance and strength trained) and 376 control subjects. After data pooling, FMD was higher in athletes than that in control groups (SMD, 0.48; P = 0.008). In subgroup analyses, young athletes (40 yr) presented increased baseline brachial artery diameter (mean difference, 0.40 mm; P0.00001) and similar FMD (SMD, 0.27; P = 0.22) compared with those in controls. In contrast, master athletes (;50 yr) showed similar baseline brachial artery diameter (mean difference, 0.04 mm; P = 0.69) and increased FMD (SMD, 0.99; P = 0.0005) compared with those in controls.The current meta-analysis provides evidence that master athletes but not young athletes exhibit greater FMD compared with that in age-matched healthy controls, thus suggesting that the association between high levels of exercise training and increased FMD is age dependent.

Introduction Metabolic syndrome (MetS), a cluster of cardiovascular risk factors, increases the incidence of type 2 diabetes (DB2). And among them, obesity, defined as the expansion of white adipose tissue (AT), which stores excessive energy intake, is associated to vitamin D (vitD) deficiency. Aside, growing evidences suggest that physical activity (PA) is efficient to reduce MetS and its associated complications. Objectives The aim of the study was to assess the impact of PA associated with vitD supplementation on MetS cardiovascular risk factors. Method In this context, C57/bl6 mice (n = 110) were fed with an obesogenic high fat/high sucrose (HFS) diet during 10 weeks. Then, mice underwent PA and vitD supplemented HFS diet during 15 weeks. Mice were monitored for weight, glucose and insulin tolerance and maximum aerobic capacity up to 25 weeks of protocol, and plasma and AT were collected after sacrifice. Results PA reduced significantly weight gain (−20%), adiposity (−23%) and enhanced physical performances (+26%) compared to HFS mice. VitD supplementation associated to PA did not provide additional benefits on these parameters. Nevertheless, insulin sensitivity was significantly improved after 15 weeks of PA + vitD supplementation, with a normalization to control mice values. On the other hand, inguinal AT gene expression analysis revealed: – a reduced inflammation, with pro-inflammatory mediators MCP1 (CCL-2) and RANTES (CCL-5) decreased mRNA levels; – increased lipid oxidation metabolism with PGC1-a (Peroxisome proliferator-activated receptor gamma coactivator 1-alpha) and CPT1b (Carnitine Palmitoyltransferase-1b) increased mRNA levels after PA + vitD in comparison to inguinal AT from HFS mice. Conclusions Our study underlines that PA associated to vitD supplementation prevent DB2 development in obese mice, with a decrease of inflammation and enhanced lipid catabolism in AT. More analysis is undergoing to characterize the mechanisms involved.

Background Discrepancies are present in the literature on resting myocardial mechanics in patients with uncomplicated type 2 diabetes mellitus (T2DM). Data are noticeably sparse regarding circumferential function and torsional mechanics. Resting deformation imaging may not be sensitive enough to detect subtle dysfunctions. The aim of this study was thus to comprehensively evaluate myocardial mechanics in patients with T2DM at rest and to investigate whether dobutamine stress echocardiography could unmask functional alterations that would remain otherwise subtle at rest. Methods Forty-four patients with T2DM and 35 healthy control subjects of similar age and sex were prospectively recruited. After conventional echocardiography, myocardial mechanics was evaluated at rest and during low-dose dobutamine stress echocardiography (target heart rate, 110 beats/min). Results Patients with T2DM presented with altered global diastolic function but preserved systolic function. Deformation imaging indexes were similar between groups at rest, but significant differences were noticed under dobutamine infusion ( Table 1 ). Multivariate analysis identified epicardial fat, dyslipidemia, and fasting glycaemia as significant contributors to the changes from rest to dobutamine. Conclusion These findings demonstrate the usefulness of dobutamine stress echocardiography in establishing impairments in myocardial mechanics in patients with uncomplicated T2DM. Systemic metabolic disturbances and epicardial fat act as the main contributors to the blunted response to dobutamine stress in these patients.

AB Introduction: Prolonged and strenuous exercise (PSE) induces transient left ventricular (LV) dysfunction. Although a consensus exists regarding the decrease in diastolic function, the existence of a decrease in systolic function by a PSE remains controversial, probably due to the transient tachycardia and changes in loading conditions observed upon the completion of exercise. Therefore, the objective was to evaluate LV systolic function before and after a PSE using two-dimensional speckle tracking echocardiography not only at rest but also during incremental tests to adjust heart rates (HR). Methods and Results: Sixteen healthy young men (23 +/- 3 yr old) performed a 3-h period of intensity-controlled upright cycling. LV strain (S), systolic strain rate (SR), rotation, and systolic rotational rate were evaluated by two-dimensional speckle tracking echocardiography before and after a 3-h period of PSE at rest and during incremental tests. Posttest evaluation was performed once the HR had returned to the pretest value. Under resting conditions, parameters of systolic function were either unchanged or increased after the PSE. However, during the incremental test, all LV systolic SR and apical rotational rates were decreased after PSE (radial SR at workload 3 (W3): 2.21 +/- 0.12.s-1 vs 1.87 +/- 0.10.s-1, P < 0.01 and apical rotational rate at W3: 128 +/- 28 deg.s-1 vs 105 +/- 26 deg.s-1, P < 0.05). Regression analyses between LV systolic SR and HR showed lower y-intercepts without differences in slopes, suggesting a decrease of both global and regional systolic functions irrespective of HR after the PSE. Conclusion: Our findings based on LV S and SR data during incremental tests demonstrate that the 3-h period of PSE induces LV systolic dysfunction

Objective Recent findings indicated silent incipient myocardial dysfunction in juvenile obesity despite normal global cardiac function. The present study investigated whether lifestyle intervention is able to favorably impact these obesity-related myocardial abnormalities and whether improvements are related to changes in insulin resistance and cardiac remodeling. Design and Methods Twenty-eight severe obese adolescents (OB) participated in a 9 month lifestyle intervention program (LIP) based on aerobic exercise and diet. Twenty healthy adolescents (CG) served as controls. Conventional echocardiography and myocardial mechanics were obtained at baseline and follow-up along with insulin resistance. Results Insulin sensitivity improved (P < 0.001) and body weight decreased (P < 0.001) consecutive to LIP. At baseline, OB had depressed longitudinal (L) strain (CG: −18.3 ± 2.6, OB: −14.2 ± 3.6%, P < 0.001) and enhanced twist compared to controls. The LIP in OB restored L strain to normal values (−16.9 ± 3.5%, NS), whereas it did not affect twist mechanics. From stepwise multiple regression analysis, only baseline L strain and changes in BMI Z-score (r2-adjusted = 0.49, P < 0.001) emerged as independent predictors of L strain changes. Conclusions Juvenile obesity is associated with myocardial mechanic abnormalities that can be partly corrected by lifestyle intervention. Restoration of longitudinal myocardial function occurs in the absence of left ventricular remodeling changes and is not associated with insulin resistance improvements.

Objective The aim of the study is to characterize left ventricular (LV) myocardial mechanics in adults with metabolic syndrome (MetS), and elucidate the effects of multiple risk-factors on myocardial function using speckle tracking echocardiography (STE); a more sensitive method than conventional echocardiography for detecting subclinical myocardial dysfunction. Design and Methods Cross-sectional analyses of 92 adults (50–70 years) with MetS, and 50 healthy controls included conventional echocardiography, blood biochemistry, and STE-derived myocardial longitudinal, circumferential, and twist mechanics. Results Using conventional measures, MetS participants revealed LV hypertrophy and reduced diastolic function compared with controls, while systolic function was preserved. From STE, MetS participants showed attenuated longitudinal strain (−16.8% ± 2.8% vs. −20.6% ± 2.7%), and both diastolic (1.1 ± 0.2 vs. 1.4 ± 0.3 s s−1) and systolic (−1.0 ± 0.1 vs. −1.2 ± 0.2 s s−1) strain rate (SR). Circumferential strain, SR, and twist mechanics did not differ. Participants with the highest number of MetS factors or diabetes demonstrated the greatest reduction in longitudinal strain and SR. Abdominal obesity, TNF-α, HbA1c, and systolic dyssynchrony explained 48% of impairment in longitudinal strain. Conclusions Impaired longitudinal myocardial diastolic and systolic function, but preserved circumferential function and twist mechanics were found in MetS participants, indicative of altered subendocardial function. This dysfunction was best predicted by abdominal obesity, inflammation, glucose-intolerance, and systolic dyssynchrony.

Aims: The purpose of our study was to determine the effect of lifestyle intervention on left ventricular (LV) regional myocardial function in patients with metabolic syndrome (MetS) and investigate the relationships of the changes in myocardial function to changes in epicardial adipose tissue (EAT), inflammatory profile and MetS components. Methods: Eighty-seven MetS patients were enrolled in a 6 month lifestyle intervention program based on dietary management and increased physical activity, and compared with 44 aged and sex-matched healthy controls. MetS individuals were allocated to different groups randomized (computer-generated randomization) on exercise modalities (high-intensity dominant resistance or aerobic training, and moderate-intensity of both modes). EAT was measured by transthoracic echocardiography and LV longitudinal strains and strain rates were obtained using vector velocity imaging. Blood chemistry allowed assessments of adipocytokines (TNF-α: tumor necrosis factor α, PAI active: active plasminogen activator inhibitor-1 and adiponectin) and glucose tolerance markers. Results: Regardless of exercise training modalities, lifestyle intervention improved significantly LV strains and strain rates (p < 0.001) as well as metabolic and inflammatory profiles. Stepwise multiple regression analyses revealed EAT (β = 0.73, p < 0.01), log adiponectin (β = − 0.13, p < 0.05) and log TNF-α (β = 0.15, p < 0.05) as independent predictors of LV longitudinal strain (R2 = 0.74, p < 0.001) while myocardial function improvement consecutive to lifestyle intervention was explained by EAT changes only (R2 = 0.54, p < 0.001). Conclusion: The mechanisms through which regional myocardial function is impaired in MetS and improved consecutive to intervention involved EAT, possibly via paracrine effects of adipocytokines. EAT should be considered as a future therapeutic target of interest in the treatment of metabolic-related cardiac diseases.

Hydroxytyrosol (HT) is known to be a strong polyphenolic antioxidant of olive oil. However, its in vivo effects are controversial since intestinal absorption is low and it is highly metabolized into glucuronides (GC), suggesting that these metabolites could be responsible of HT biological activity in vivo . Our objectives were to study the direct effects of HT and its glucuronides on vascular function and the oxidative stress vascular protection on healthy and diabetic rats The vascular function was assessed on aortas from diabetic-High Fat Sucrose diet (HFS) and age-matched (22 weeks) control fed with a standard diet (SD) Wistar rats, in comparison to young (9 weeks) control Wistar rats (ySD). The endothelium-dependent and independent vasorelaxing effects of these compounds were assessed via incremental doses of HT and GC (10 -9 to 10 -4 M) and compared to Resveratrol (Res). Expression and phosphorylation of Ser 1177 eNOS were measured by Western blot. To evaluate the anti-oxidative effects of these polyphenols (100 μM, 5min), vascular function was assessed in presence/absence of t -BOOH (500μM, 30min). HT and GC did not show any endothelium-dependent and independent vasorelaxation effects in ySD and HFS rats while Res produced vasorelaxing effect at 10 -4 M in all groups of rats and no vasorelaxant effects were noticed in SD rats. The overall absence of vasorelaxing effect can be explained by the lack eNOS phosphorylation. As for the antioxidative properties, HT, GC and Res increased significantly endothelium-dependent relaxation in comparison of aorta rings treated only with t -BOOH (79.9%±9.2, 74.1%±8.6, 71.0%±8.2, 48.4%±5.3 respectively). In addition, co-incubation of HT/GC and Res/GC increased even more the vasorelaxation under pro-oxydant conditions. In diabetic HFS rats, (i) the incubation for 5min with HT and GC did not improve neither vasorelaxation nor the contraction; (ii) however, a prolonged 30 min incubation resulted in more pronounced and significant contractile (64.8%±12.4 and 95.6%±16.3, respectively) and endothelium-dependent relaxation effects (30%±7.5 and 58.1%±10.3 respectively) for GC in comparison to HT. In conclusion, GC seems to be responsible for the anti-oxidative properties of olive oil but further experimentations have to be realized concerning its possible interconversion in HT by β-glucuronidase. The author hereby declares no conflict of interest

Background— Abnormal left ventricular (LV) deformational mechanics have been demonstrated in patients with hypertrophic cardiomyopathy (HCM) at rest, but there is a lack of information on their adaptation to exercise. The aim of this study was to assess the adaptability of LV strains and torsional mechanics during exercise in HCM patients. Methods and Results— Twenty nonobstructive HCM patients (age, 48.3±12.3 years; 14 men) and 20 control subjects underwent speckle-tracking echocardiographic measurement of longitudinal, radial, and circumferential strains, systolic twist, and diastolic untwisting rate (UTR) at rest and submaximal exercise. HCM patients showed lower resting longitudinal (−15.7±5.0% versus −19.4±2.6%, P P P P P P P =0.68). Conclusions— HCM patients had severely limited strain adaptability and no LV twisting reserve at exercise. They had reduced and delayed UTR with reduced systolic-diastolic coupling efficiency by twist-untwist mechanics.

International audience; Objective: Although increased blood flow (BF) in exercising muscles is thought to be impaired in obese subjects and may contribute to physical inactivity, data are scarce in this regard and the involvement of endothelium dysfunction remains partly hypothetical. Methods: A total of 16 middle-aged obese men (body mass index, BMIX30 kg m À2) and 16 normal-weight men (BMIo25 kg m À2), matched for age, were recruited. We used ultrasonography to compare intima-media thickness (IMT) and distensibility of the carotid artery, flow-mediated dilation (FMD), nitrate-dependent dilation (NDD) and peak BF during post-ischemic hyperemia in the brachial artery (a conduit artery), and leg BF during knee-extensor exercise (indicative of resistance vessel function) in obese and in normal-weight men. In addition, 10 obese men participated in an 8 week individualized low-intensity training program. Results: Compared with normal-weight men, obese men had higher carotid IMT (0.50 ± 0.01 vs 0.62 ± 0.04 mm, Po0.05) but lower carotid distensibility (0.26±0.03 vs 0.11±0.03 mm Hg À1 10 À2 , Po0.05), FMD (5.7±0.4 vs 3.3±0.5%, Po0.05) and peak BF during post-ischemic hyperemia (398 ± 52 vs 229 ± 24%, Po0.05), despite similar maximal shear rate, without NDD differences. Lower limb BF (ml min À1 100 g À1) increased significantly from rest to maximal exercise in both groups with lower values in obese men (at peak power, 36.9 ± 1.6 vs 31.5 þ 2.2 ml min À1 100 g À1 , Po0.05). Exercise training normalized carotid distensibility (0.14±0.04 before vs 0.23±0.03 mm Hg À1 10 À2 after training, P ¼ 0.09) and FMD (2.7±0.4 before vs 4.8±0.5% after training, Po0.05), but did not improve brachial post-ischemic peak BF or exercising leg BF. Conclusions: In obese men, conduit and resistance vessel reactivity is depressed, but a short-term low-intensity exercise training improves distensibility and endothelium dependent vasodilation in the large conduit artery, but not post ischemic or exercise muscle BF.

The contraction of cardiomyocytes induces a systolic increase in left ventricular (LV) normal (radial, circumferential and longitudinal) and shear strains, whose functional consequences have not been evaluated, so far, in athletes. We used 2D ultrasound speckle tracking imaging (STI) to evaluate LV regional strain in high-level cyclists compared to sedentary controls. Sixteen male elite cyclists and 23 sedentary controls underwent conventional, tissue Doppler, and STI echocardiography at rest. We assessed LV long and short axis normal strains and shear strains. We evaluated circumferential–longitudinal shear strain from LV torsion, and circumferential–radial shear strain from the difference between subendocardial and subepicardial torsion. Apical radial strain (42.7 ± 10.5%versus 52.2 ± 14.3%, P < 0.05) and LV torsion (6.0 ± 1.8 deg versus 9.2 ± 3.2 deg, P < 0.01) were lower in cyclists than in controls, respectively. Rotations and torsion were higher in the subendocardial than in the subepicardial region in sedentary controls, but not in cyclists. Haemodynamic and tissue Doppler based indexes of global LV diastolic and systolic functions were not different between cyclists and controls. Athlete's heart is associated with specific LV adaptation including lower apical strain and lower myocardial shear strains, with no change in global LV diastolic and systolic function. These mechanical alterations could improve the cardiovascular adjustments to exercise by increasing the radial strain and torsional (and thus untwisting) response to exercise, a key element of diastolic filling and thus of cardiac performance in athletes.

AIM To determine whether endurance training can counterbalance the negative effects of hypoxia on mitochondrial phosphorylation and expression of the long chain mitochondrial fatty acid transporter muscle carnitine palmitoyl transferase 1 (mCPT-1). METHODS Male Wistar rats were exposed either to hypobaric hypoxia (at a simulated altitude of approximately 4000 m, PIO(2) approximately 90 mmHg) or to normoxia (sea level) for 5 weeks. In each environment, rats were randomly assigned to two groups. The trained group went through a 5-week endurance training programme. The control group remained sedentary for the same time period. Muscle fatty acid oxidation capacity was evaluated after the 5-week period on isolated mitochondria prepared from quadriceps muscles with the use of palmitoylcarnitine or pamitoylCoA + carnitine. RESULTS Chronic hypoxia decreased basal (V(0), -31% with pamitoylCoA + carnitine and -21% with palmitoylcarnitine, P < 0.05) and maximal (V(max), -31% with pamitoylCoA + carnitine, P < 0.05) respiration rates, hydroxyacylCoA dehydrogenase activity (-48%, P < 0.05), mCPT-1 activity index (-34%, P < 0.05) and mCPT-1 protein content (-34%, P < 0.05). Five weeks of endurance training in hypoxia brought V(0), mCPT-1 activity index and mCPT-1 protein content values back to sedentary normoxic levels. Moreover, in the group trained in hypoxia, V(max) reached a higher level than in the group that maintained a sedentary lifestyle in normoxia (24.2 nmol O(2). min(-1) . mg(-1) for hypoxic training vs. 19.9 nmol O(2) . min(-1) . mg(-1) for normoxic sedentarity, P < 0.05). CONCLUSION Endurance training can attenuate chronic hypoxia-induced impairments in mitochondrial fatty acid oxidation. This training effect seems mostly mediated by mCPT-1 activity rather than by mCPT-1 content.

Although cardiotoxic effects of highly active antiretroviral therapy (HAART) are a growing concern, there is a lack of prospective studies of subclinical involvement of the heart in human immunodeficiency virus (HIV)-infected patients. This study evaluated noninvasively cardiac morphologic characteristics and function in HIV-positive (HIV(+)) men receiving HAART for > or =2 years with no clinical evidence of cardiovascular disease. Echocardiography at rest, including tissue Doppler imaging and exercise testing, were performed in 30 HIV(+) men (age 42.1 +/- 4.7 years, duration of HIV infection 10.4 +/- 4.7 years, duration of HAART 5.3 +/- 2.1 years) and 26 age-matched healthy controls. At rest, HIV(+) patients had similar left ventricular (LV) mass indexed to height(2.7) (40.6 +/- 9.5 vs 37.5 +/- 9.3 g/m; p >0.05), but a higher prevalence of LV diastolic dysfunction (abnormal relaxation or pseudonormal filling pattern in 64% of patients vs 12% of controls; p

International audience; Hypoxia-induced pulmonary hypertension is associated with an impairment of nitric oxide-mediated vasorelaxation in the pulmonary circulation that is not prevented by exercise training. The present study was designed to test the hypothesis that a decrease in l-arginine bioavailability could be involved in this blunted response to exercise training. Male Wistar rats were randomly assigned to 4 groups: normotensive sedentary, normotensive trained, pulmonary hypertensive sedentary, pulmonary hypertensive trained. Pulmonary hypertension was induced by chronic exposure to hypobaric hypoxia (PIO(2) approximately 90 mmHg). Endothelium-dependent vasorelaxation to acetylcholine (10(-8)-10(-4) M) with or without l-arginine (10(-3) M) and/or nitro-l-arginine methyl ester (5.10(-6) M) was assessed on isolated pulmonary arterial rings. Maximal relaxation to acetylcholine was impaired in both pulmonary hypertensive groups. Acute l-arginine supplementation improved acetylcholine-induced vasorelaxation in the pulmonary hypertensive trained rats (P

The stresses during the secondary-drying stage of lyophilization were investigated using a controlled humidity mini-freeze-dryer [Luthra S, Obert J-P, Kalonia DS, Pikal MJ. 2007. Investigation of drying stresses on proteins during lyophilization: Differentiation between primary and secondary-drying stresses on lactate dehydrogenase using a humidity controlled mini freeze-dryer. J Pharm Sci 96: 61-70.]. Lactate dehydrogenase (LDH), was formulated in: (1) Tween 80, (2) citrate buffer, and (3) both Tween 80 and citrate buffer. Protein activity recovery was measured as a function of relative humidity (RH), product temperature, and drying duration. Studies were also conducted with different concentrations of sucrose, sorbitol, and poly (vinyl pyrrolidone) (PVP). LDH stability was affected to a small extent by RH and significantly by drying temperature and duration. Complete stabilization of LDH was observed when lyophilized with sucrose and PVP but only a partial stabilization was observed with sorbitol. The mini-freeze-dryer enabled studying the process parameters independently, unlike a conventional study where these effects are generally convoluted. The results suggest that the stability of the protein is a function of the dynamics of the system during lyophilization. The origin of the stabilization effect of sucrose, which could, in principle, be attributed both to direct interaction with the protein or vitrification of the protein was elucidated using lyoprotectants that can either hydrogen bond well with the protein (sorbitol) or form a good glass (PVP). It appears both effects are required for complete stabilization of the protein.

Aim Specific cardiac adaptations leading to lack of improvement in left ventricular (LV) filling have been recently established consecutive to altitude training (AT). The aim of this study was to investigate the contribution of LV relaxation properties, preload and dimensions in the explanation of this hypoxia (with or without training)-induced absence of LV filling enhancement. Methods Male rats were randomly assigned to four groups: Normoxic groups (PIO2 = 159 mmHg) with (NT) or without (N) training, and hypoxic groups (PIO2 = 110 mmHg) with (CHT) or without training (CH). Cardiac adaptations were evaluated by Doppler-echocardiograhy, cardiac weighing, aortic pulsed-Doppler transducer and intraventricular pressure variations. Results Our major finding was that the lack of LV filling improvement consecutive to AT was not accounted for by deleterious effects of hypoxia exposure on LV relaxation properties but rather explained by altitude-induced cardiac morphological and preload alterations.

The present study was conducted to investigate both skeletal and somatic developments in a group of highly trained prepubertal girl gymnasts at the beginning of their peak bone mass acquisition. The experimental group included 14 gymnasts who had trained 12—15 h per wk for 3 y before starting the study. The control group consisted of 15 non-exerciser children and 6 swimmers training for 5—6 h/wk. Body composition and bone mineral density (BMD) of the total body, lumbar spine, non-dominant hip and radius were measured using dual-energy X-ray absorptiometry. Calculation of bone age and measurement of body height and weight were done. All measurements and analyses were carried out twice with a 1-y interval by the same technician. There were no differences between groups in age, bone age, body height and weight and lean tissue mass at the start of the study and 1 y later. The somatic changes observed between the first and second years tended to be greater in gymnasts compared to controls, except for body height. At the first and second investigations, BMD values in the gymnasts were statistically higher than in the controls at all skeletal sites, but not for the whole body (from p < 0.05 to p < 0.001, depending on the site). Percentage changes in BMD pre-investigation compared with post-investigation tended to be greater in gymnasts. Variations in lean mass, bone age and fat mass were found to be the best independent predictors of annual changes in BMD for total body, lumbar spine, trochanter and femoral neck sites. These results suggested that high-volume impact loading training could promote a higher annual gain in bone mineral acquisition at the strained body sites in prepubertal girls without affecting somatic growth dimensions. □Bone mass, growth, gymnasts, prepubertal training, somatic development

UNLABELLED The aim of this study was to examine the effect of two endurance training regimens of varying duration and frequency on maximal oxygen uptake (VO2max) of prepubertal boys and girls. The subjects consisted of 84 prepubertal children, aged 10-11 y. Two groups, EG1 (n = 36) and EG2 (n = 20), were involved in a 13 wk endurance training programme (intensity: higher than 80% of maximal heart rate for both groups; frequency: 3 and 2 sessions per week: duration: 25-35 min and 15-20 min per session in the target zone, for EG1 and EG2, respectively). Another group of 28 children served as a control group. Each subject performed a continuous and progressive exercise test to exhaustion on a cycle ergometer to evaluate VO2max before and after the 13 wk study period. The main findings of this study were: (i) there was no improvement in VO2max after a training programme with the following characteristics: 2 sessions per week with 15-20 min of exercise performed at an intensity higher than 80% of maximal heart rate; (ii) a VO2max enhancement (on average +7%) was seen only in children who participated in a training programme organized on the basis of three sessions per week during which exercise intensities higher than 80% of maximal heart rate were sustained for at least 25 min per session; and (iii) there was no gender difference in the training response. CONCLUSION It appeared from this longitudinal study that only a programme with continuous activity, organized on the basis of three sessions per week, with 25-35 min at an intensity higher than 80% of maximal heart rate at each session, enhanced VO2max in prepubertal boys and girls.

The aim of the present study was to investigate the gender effect of an endurance training programme on the maximal oxygen uptake (VO2max) of prepubertal children. The subjects comprised eighty-five 10-11-y-old prepubertal children: 35 (17 girls, 18 boys; EG) were involved in a 13-wk running training programme and 50 (22 girls, 28 boys; CG) served as a control group. Each subject carried out a continuous and progressive cycle ergometer test before and after the 13-wk study period under the same conditions and procedures. Oxygen consumption, carbon dioxide, ventilation and heart rate (HR) were continuously monitored during the test. The training programme consisted of interval and continuous long-distance running (frequency: 3 times a week, duration: 1 h per session, intensity: higher than 80% of maximal HR). V02max significantly increased after the training programme for EG (before = 42.3 +/- 7.7, after = 45.3 +/- 7.5 ml x min(-1) x kg(-1), p < 0.01), while no alterations were noticed for CG (before = 43.1 +/- 6.7, after = 42.6 +/- 7.6 ml x min(-1) x kg(-1), p < 0.01). Such an increase was higher in the girls (+9.1%) than the boys (+4.6%). The lower initial fitness of the girls could explain this, however, because a significant relationship was found between the percentage of VO2max increase after training and the initial VO2max. The present longitudinal study shows that maximal oxygen uptake can increase in prepubertal children after an aerobic training programme and that such an increase is of the same order in boys and girls when the initial aerobic fitness is taken into account.

This article describes the design, performance testing, and application of a controlled humidity mini-freeze-dryer in studying the physical stability of lactate dehydrogenase during lyophilization. Performance evaluation of the mini-freeze-dryer was conducted with tests, namely water sublimation, radiation heat exchange, lowest achievable temperature, and leak testing. Protein stability studies were conducted by comparing protein activity at various stages of lyophilization with the initial activity. The shelf and condenser temperature were stable at

International audience; , Reboul C. Carbon monoxide increases inducible NOS expression which mediates CO-induced myocardial damage during ischemia-reperfusion..—We investigated the role of inducible nitric oxide (NO) synthase (iNOS) on ischemic myocardial damage in rats exposed to daily low nontoxic levels of carbon monoxide (CO). CO is a ubiquitous environmental pollutant that impacts on mortality and morbidity from cardiovascular diseases. We have previously shown that CO exposure aggravates myocardial ischemia-reperfusion (I/R) injury partly because of increased oxidative stress. Nevertheless, cellular mechanisms underlying cardiac CO toxicity remain hypothetical. Wistar rats were exposed to simulated urban CO pollution for 4 wk. First, the effects of CO exposure on NO production and NO synthase (NOS) expression were evaluated. Myocardial I/R was performed on isolated perfused hearts in the presence or absence of S-methyl-isothiourea (1 ␮M), a NOS inhibitor highly specific for iNOS. Finally, Ca 2ϩ handling was evaluated in isolated myocytes before and after an anoxia-reoxygenation performed with or without S-methyl-isothiourea or N-acetylcystein (20 ␮M), a nonspecific antioxidant. Our main results revealed that 1) CO exposure altered the pattern of NOS expression, which is characterized by increased neuronal NOS and iNOS expression; 2) cardiac NO production increased in CO rats because of its overexpression of iNOS; and 3) the use of a specific inhibitor of iNOS reduced myocardial hypersensitivity to I/R (infarct size, 29 vs. 51% of risk zone) in CO rat hearts. These last results are explained by the deleterious effects of NO and reactive oxygen species overproduction by iNOS on diastolic Ca 2ϩ overload and myofilaments Ca 2ϩ sensitivity. In conclusion, this study highlights the involvement of iNOS overexpression in the pathogenesis of simulated urban CO air pollution exposure. nitric oxide; myocardial infarction; carbon monoxide; nitric oxide synthase