The interplay of footwear and exercise-induced fatigue on substrate partitioning and energy cost of running during steady-state running exercise

The purpose of this study was to assess the interplay of footwear and exercise-induced fatigue (EIF) on substrate partitioning and energy cost of running during steady-state running exercise. Ten trained male distance runners partook first in an incremental test 7 days prior to the experimental session. Participants performed three 8 min treadmill runs in randomized order in minimalist and shod footwear prior to and immediately after an EIF protocol. Cardiorespiratory parameters, substrate partitioning, RPE and blood lactate were measured throughout the experimental sessions. No significant difference was observed pre- to post-EIF on VO₂ during Cr, although VCO₂ production showed a trend towards significance (p = 0.063). Furthermore, there was no significant effect of footwear but there was significant main effect of time (pre- vs. post-EIF) on CHO (p = 0.003) and lipid (p =0.004) oxidation. The caloric cost of running showed no significant difference from pre- to post-EIF (0.98±0.14, 1.00±0.14). Ultimately alteration in substrate contribution to energy production plausibly stems from muscle glycogen depletion. Although not measured muscle glycogen has certainly greatly contributed to maintain running performance during EIF. This is supported by indirect markers of fatigue such as lactate production, RPE score and peak HR

Exercise and the heart : effects of exercise training on coronary artery disease and on myocardial function, metabolism and vulnerability to ventricular fibrillation

There is epidemiological and experimental evidence suggesting that exercise training may reduce the mortality rate from coronary heart disease, in particular the sudden death rate, and that it may improve the peak functional capacity of the heart. This thesis includes experimental work that is relevant to both these questions

Les effets de l'augmentation de la masse adipeuse sur la fonction cardiovasculaire ex vivo en fonction du stress oxydant et de la fonction mitochondriale (rôle du vieillissement du régime alimentaire)

Le surpoids et l'obésité, en constante augmentation à l'échelle mondiale à un rythme exponentiel, conduit au développement du syndrome métabolique et du diabète de type 2. Plusieurs études ont mis en évidence l'association entre l'excès de masse grasse, en particulier dans la région abdominale, et le développement des maladies cardiovasculaires. Une telle augmentation de masse grasse corporelle caractérise le vieillissement normal, qui est considéré per se comme un facteur de risque majeur pour les maladies cardiovasculaires. De plus, dans le monde industrialisé, l'incidence des maladies cardiovasculaires est encore plus élevée et fortement liée aux habitudes occidentales (régimes obésogènes, sédentarité) qui contribuent à l'accumulation de la graisse abdominale. L'objectif général de ce travail consiste à suivre les changements corporels qui surviennent entre la jeunesse et l'âge moyen où commence à survenir les complications cardio-vasculaires et à savoir comment l'obésité induite par l'alimentation peut modifier ces aspects. Dans un premier temps, nous avons montré que les coeurs des rats Wistar d'âge moyen sont caractérisés par une moindre restauration de l'activité mécanique cardiaque au cours de la réperfusion post-ischémique en raison de perturbations de la perfusion coronaire et d'une insuffisance de l'apport en oxygène. La présence d'un stress oxydant systémique suite à l'augmentation de la masse grasse survenant entre la jeunesse et l'âge adulte est également en cause. Une diminution progressive de la dilatation endothélium-dépendante des microvaisseaux coronaires est également observé avec le vieillissement, ce qui résulte d'une évolution différentielle du comportement fonctionnel des cellules endothéliales et musculaires lisses apparemment liée au métabolisme énergétique et au stress oxydant. L'obésité induite par un régime riche en graisse provoque un certain nombre de modifications corporelles, métaboliques et cardiovasculaires au cours de cette période du vieillissement. L'excès de masse grasse abdominale induit une augmentation du stress oxydant aux niveaux systémique, cytosolique et mitochondrial accompagné par des altérations biochimiques concernant le métabolisme du glucose et les niveaux plasmatiques de cholestérol et de triglycérides. L'obésité induite par une hyperphagie et la présence d'un diabète de type 2 chez les rats Zucker obèses diabétiques provoque également une insulino-résistance sévère. Ces deux modèles d'obésité sont caractérisés par une diminution de la fonction cardiaque ex vivo liée au métabolisme énergétique mitochondrial et au stress oxydant. En outre, ils sont tous les deux caractérisés par une adaptation des microvaisseaux coronaires dont la réactivité est augmentée dans le cas de régime riche en graisse et maintenue dans le cas du diabète. Ces adaptations sont dues à des mécanismes différents dans les deux modèles d'obésité. Elles permettent de mieux répondre aux exigences métaboliques élevées liées à l'obésité. En conclusion, notre travail montre que les caractéristiques corporelles et métaboliques, le métabolisme énergétique mitochondrial, la fonction cardiaque et la réactivité coronaire sont modifiés lors du vieillissement dans les conditions normales ou obésogènes. Ces résultats encouragent la recherche ultérieure des mécanismes mis en jeu. Les interventions visant à réduire la masse grasse, qu'elle soit spontanément accrue par l'âge ou qu'elle résulte du régime alimentaire, seraient d'un grand intérêt pour retarder les complications cardiovasculaires.The prevalence of overweight and obesity is increasing worldwide at an alarming rate leading to the development of metabolic syndrome and diabetes mellitus. Previous studies have highlightened the association between fat accumulation, especially in the abdominal area, and the development of cardiovascular diseases. An increase in body and fat mass characterizes normal aging, which is considered per se the major risk factor for cardiovascular diseases. In the industrialized societies, the incidence of cardiovascular diseases occurring with age is even more increased due to the Western-world lifestyle habits (e.g. obesogenic diets, sedentariness) that contribute to excess fat accumulation. Accordingly, the overall goal of this work was to understand how body changes occurring from youth to middle age were related to middle age cardiovascular complications and how diet-induced obesity altered these aspects. Initially, we demonstrated that in normal aging middle-aged hearts of Wistar rats were characterized by lower restoration of the cardiac mechanical activity during reperfusion ex vivo due to impaired recovery of the coronary flow and insufficient oxygen supply. This was also related to the presence of increased systemic oxidative stress following the increase in fat mass that occurred from youth to young adulthood. A progressive decline in the endothelium-dependent dilatation of the coronary microvasculature also occurred with aging, which was due to different functional behaviours of the endothelial and smooth muscular cells, which appeared to be related to the energy metabolism and oxidative stress. High-fat diet-induced obesity triggered a number of alterations in the body, metabolic and cardiovascular characteristics of the animals during this aging period. The excess abdominal fat accumulation provoked the increase of oxidative stress at the systemic, cytosolic and mitochondrial levels accompanied by biochemical alterations in the glucose and lipid metabolisms such as hypercholesterolemia and hypertriglyceridemia. The hyperphagia-induced obesity and the related type 2 diabetes in the Zucker diabetic fatty rats provoked also severe insulin resistance. Both models of diet-induced obesity were characterized by decreased ex vivo cardiac function related to mitochondrial energy metabolism and oxidative stress. Furthermore, they were both characterized by an adaptation of the coronary microvasculature whose reactivity was enhanced in the first case and maintained in the second, in order to meet the elevated metabolic demands of the hearts due to obesity. These adaptations were due to different mechanisms in these two models of obesity. In conclusion, our work revealed a temporal pattern of changes concerning the body and metabolic characteristics, mitochondrial energy metabolism, cardiac function and coronary microvascular reactivity that occur from youth to middle age either under normal or obesogenic-related conditions. These results encourage further research in order to explain the mechanisms related to these alterations. Interventions aiming at reducing the fat mass that increases with age or diet would be of great interest in an effort to delay the cardiovascularSAVOIE-SCD - Bib.électronique (730659901) / SudocGRENOBLE1/INP-Bib.électronique (384210012) / SudocGRENOBLE2/3-Bib.électronique (384219901) / SudocSudocFranceF

Phospholipases: From Structure to Biological Function

Phospholipases are a ubiquitous group of enzymes that hydrolyze ester bonds within membrane phospholipids. These enzymes serve multiple biological functions that go far beyond a mere membrane remodeling role in cellular homeostasis; they also play key functions in nutrient digestion and the regulated formation of bioactive lipids involved in cell signaling. It is to the latter function, critical to life, that this book is primarily concerned with. All the chapters are written by renowned experts in the area, and provide forefront information on the role phospholipases in a number of physiological and pathophysiological settings

A system wide study on the hypertrophic response to salbutamol in skeletal muscle cells

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A comparative study of acute responses to running in elite black and white marathon athletes

Experienced male marathon runners, 9 black and 10 white, with marathon times of 2 hours 45 minutes or faster, acted as subjects for the study, the purpose of which was to determine whether black runners are better suited to marathon running than whites. Body composition was determined by anthropometry. Maximal oxygen uptake (VO₂ max) and other physiological variables were measured during a continuous, speed-incremented treadmill protocol using a computer-aided data acquisition system. Subjects also ran a simulated marathon at 92.5% of the running speed at which the ventilatory threshold (VT) occurred. Physiological, gait and RPE variables were measured at 10 minute intervals during the marathon. Major findings are detailed below:- The VO₂, max averaged 60.4 ∓ 6.5 and 63.2 ∓ 2.9 mI. kg⁻¹.min⁻¹ in the black and white runners respectively and was highly correlated with best marathon race time (r = 0.86 and 0.85 respectively) and VT (r = 0.84 and 0.60 respectively) (p < 0.05). No significant differences existed between the groups in submaximal oxygen uptake (VO₂,) or % VO₂ max utilised at 16 km.hr⁻¹, but the estimated % VO₂ max utilised during a marathon race was higher in the black (89.0 ∓ 5.5%) than the white runners (81. 5 ∓ 3.1%) {p .( 0.05). The % VO₂ max utilised at 16 km.hr⁻¹ (84.8 ∓ 9.1 and 78.6 ∓ 5.8% in the black and white runners respectively) was significantly correlated with the % VO₂, max utilised while racing in the white (81.5 ∓ 3.1%) (r = 0.70) (p < 0.05), but not the black runners (89.0 ∓ 5.5%). The VT occurred at 82.7 ∓ 7.7 and 75.6 :∓ 6.2% VO₂; max in the black and white groups respectively (p < 0.05). Post-marathon blood lactic acid levels were lower in the black (1.30 ∓ 0.26 mmo1.l⁻¹) than the white runners (1.59 ∓ 0.20 mmol.l⁻¹). The respiratory exchange ratio (R) was higher in the blacks than whites when running at 16 km.hr ⁻¹ (1.03 ∓ 0.07 and 0.98 ∓ 0.03 respectively) and during the marathon (p < 0.05). There was no significant difference in pulmonary minute ventilation (Vı) between the groups, but breathing frequency (f) was higher in the black (59 ∓ 12 breaths.min⁻¹) than the white runners (45 ∓ 8 breaths. min⁻¹ ) and tidal volume (V⊤) lower in the black ( 1.33 ∓ 0.16 l.breath⁻¹) than the white runners (1.75 ∓ 0.36 I.breath⁻¹) during submaximal running at 16 km. hr⁻¹ (p < 0.05). The same trend was observed during the marathon run. During the time-course of the marathon f increased and V⊤ decreased In both groups (p < 0.05). Stroke volume decreased and heart rate increased In both groups during the time-course of the marathon (p< 0.05). Cardiac output was therefore maintained. Thermal responses were similar in the two groups. A significant increase in rectal temperature coincided with a decrease in skin temperature and may have been related to an increase in f (r = 0.86 and 0.67 in the blacks and whites respectively), H/R (r = 0.70 and 0.67 respectively) and "local" (leg) RPE (r = 0.84 and 0.82 respectively). It was concluded that black runners were able to run marathon races at a higher % VO₂ more than whites due to the blacks having lower blood lactic acid levels when running at a similar % VO₂ max. Given similar maximal oxygen uptakes, this would enable blacks to run faster. Cardiopulmonary adjustments occur during the time-course of a marathon which maintains Q and V

Drug development progress in duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is a severe, progressive, and incurable X-linked disorder caused by mutations in the dystrophin gene. Patients with DMD have an absence of functional dystrophin protein, which results in chronic damage of muscle fibers during contraction, thus leading to deterioration of muscle quality and loss of muscle mass over time. Although there is currently no cure for DMD, improvements in treatment care and management could delay disease progression and improve quality of life, thereby prolonging life expectancy for these patients. Furthermore, active research efforts are ongoing to develop therapeutic strategies that target dystrophin deficiency, such as gene replacement therapies, exon skipping, and readthrough therapy, as well as strategies that target secondary pathology of DMD, such as novel anti-inflammatory compounds, myostatin inhibitors, and cardioprotective compounds. Furthermore, longitudinal modeling approaches have been used to characterize the progression of MRI and functional endpoints for predictive purposes to inform Go/No Go decisions in drug development. This review showcases approved drugs or drug candidates along their development paths and also provides information on primary endpoints and enrollment size of Ph2/3 and Ph3 trials in the DMD space