Effect of physical exercise on glycogen turnover and net substrate utilization according to the nutritional state.

To determine the metabolic effects of a single bout of exercise performed after a meal or in the fasting state, nine healthy subjects were studied over two 8-h periods during which net substrate oxidation was monitored by indirect calorimetry. On one occasion, exercise was performed 90 min after ingestion of a meal labeled with [U-13C]glucose [protocol meal-exercise (M-E)]. On the second occasion, exercise was performed after an overnight fast and was followed 30 min later by ingestion of an identical meal [protocol exercise-meal (E-M)]. Energy balances were similar in both protocols, but carbohydrate balance was positive (42.2 +/- 5.1 g), and lipid balance was negative (-11.1 +/- 2.0) during E-M, whereas they were nearly even during M-E. Total glycogen synthesis was calculated as carbohydrate intake minus oxidation of exogenous 13C-labeled carbohydrate (calculated from 13CO2 production). Total glycogen synthesis was increased by 90% (from 47.6 +/- 3.8 to 90.7 +/- 5.4 g, P < 0.0001) during E-M vs. M-E. Endogenous glycogen breakdown was calculated as net carbohydrate oxidation minus oxidation of exogenous carbohydrate and was increased by 44% (from 35.8 +/- 5.6 to 51.7 +/- 6.6 g, P < 0.004) during E-M. It is concluded that exercise performed in the fasting state stimulates glycogen turnover and fat oxidation.

The impact of information on patient preferences in different delivery patterns: a contingent valuation study of prescription versus OTC drugs.

OBJECTIVES: Our analysis assessed the impact of information on patients' preferences in prescription versus over-the-counter (OTC) delivery systems. METHODS: A contingent valuation (CV) study was implemented, randomly assigning 534 lay people into the receipt of limited or extended information concerning new influenza drugs. In each information arm, people answered two questions: the first asked about willingness to pay (WTP) for the new prescription drug; the second asked about WTP for the same drug sold OTC. RESULTS: We show that WTP is higher for the OTC scenario and that the level of information plays a significant role in the evaluation of the OTC scenario, with more information being associated with an increase in the WTP. In contrast, the level of information provided has no impact on WTP for prescription medicine. Thus, for the kind of drug considered here (i.e. safe, not requiring medical supervision), a switch to OTC status can be expected to be all the more beneficial, as the patient is provided with more information concerning the capability of the drug. CONCLUSIONS: Our results shed light on one of the most challenging issues that health policy makers are currently faced with, namely the threat of a bird flu pandemic. Drug delivery is a critical component of pandemic influenza preparedness. Furthermore, the congruence of our results with the agency and demand theories provides an important test of the validity of using WTP based on CV methods.

Attitude de prescription chez la femme enceinte : exemple de prise en charge d'un état dépressif

- Comment prescrire à une femme enceinte? L'attitude optimale réalise un compromis entre d'une part l'indication au traitement, et d'autre part l'importance du risque que celui-ci fait courir au foetus et à la mère. Le respect de quelques principes simples peut aider dans cette démarche: - La relative carence en connaissances dans ce domaine impose avant tout une attitude basée sur le principe de précaution. - La période (1er, 2e ou 3e trimestre) pendant laquelle le foetus sera exposé au traitement envisagé est un élément prépondérant dans la réflexion. - Le traitement de choix est celui qui, parmi les alternatives efficaces, présente le meilleur profil de sécurité pendant la grossesse selon les observations humaines disponibles. - Le rapport bénéfice/risque pour la patiente et le foetus peut s'inverser pendant la grossesse. - Toute exposition médicamenteuse problématique pendant la grossesse doit faire l'objet d'une annonce à l'un des centres suisse de pharmacovigilance. Ces données de tératovigilance sont indispensables pour alimenter les connaissances dans ce domaine. - Afin d'illustrer ces principes généraux, un exemple typique de prescription chez la femme enceinte a été choisi, mettant l'accent sur un problème de tératovigilance récemment identifié: les risques liés à certains antidépresseurs durant la grossesse.

The Effect of Adding CO2 to Hypoxic Inspired Gas on Cerebral Blood Flow Velocity and Breathing during Incremental Exercise

Hypoxia increases the ventilatory response to exercise, which leads to hyperventilation-induced hypocapnia and subsequent reduction in cerebral blood flow (CBF). We studied the effects of adding CO2 to a hypoxic inspired gas on CBF during heavy exercise in an altitude naïve population. We hypothesized that augmented inspired CO2 and hypoxia would exert synergistic effects on increasing CBF during exercise, which would improve exercise capacity compared to hypocapnic hypoxia. We also examined the responsiveness of CO2 and O2 chemoreception on the regulation ventilation (E) during incremental exercise. We measured middle cerebral artery velocity (MCAv; index of CBF), E, end-tidal PCO2, respiratory compensation threshold (RC) and ventilatory response to exercise (E slope) in ten healthy men during incremental cycling to exhaustion in normoxia and hypoxia (FIO2 = 0.10) with and without augmenting the fraction of inspired CO2 (FICO2). During exercise in normoxia, augmenting FICO2 elevated MCAv throughout exercise and lowered both RC onset andE slope below RC (P<0.05). In hypoxia, MCAv and E slope below RC during exercise were elevated, while the onset of RC occurred at lower exercise intensity (P<0.05). Augmenting FICO2 in hypoxia increased E at RC (P<0.05) but no difference was observed in RC onset, MCAv, or E slope below RC (P>0.05). The E slope above RC was unchanged with either hypoxia or augmented FICO2 (P>0.05). We found augmenting FICO2 increased CBF during sub-maximal exercise in normoxia, but not in hypoxia, indicating that the 'normal' cerebrovascular response to hypercapnia is blunted during exercise in hypoxia, possibly due to an exhaustion of cerebral vasodilatory reserve. This finding may explain the lack of improvement of exercise capacity in hypoxia with augmented CO2. Our data further indicate that, during exercise below RC, chemoreception is responsive, while above RC the ventilatory response to CO2 is blunted.

Cardiorespiratory and Cardiac Autonomic Responses to 30-15 Intermittent Fitness Test in Team Sport Players

Buchheit, M, Al Haddad, H, Millet GP, Lepretre, PM, Newton, M, and Ahmaidi, S. Cardiorespiratory and cardiac autonomic responses to 30-15 Intermittent Fitness Test in team sport players. J Strength Cond Res 23(1): xxx-xxx, 2009-The 30-15 Intermittent Fitness Test (30-15IFT) is an attractive alternative to classic continuous incremental field tests for defining a reference velocity for interval training prescription in team sport athletes. The aim of the present study was to compare cardiorespiratory and autonomic responses to 30-15IFT with those observed during a standard continuous test (CT). In 20 team sport players (20.9 +/- 2.2 years), cardiopulmonary parameters were measured during exercise and for 10 minutes after both tests. Final running velocity, peak lactate ([La]peak), and rating of perceived exertion (RPE) were also measured. Parasympathetic function was assessed during the postexercise recovery phase via heart rate (HR) recovery time constant (HRRtau) and HR variability (HRV) vagal-related indices. At exhaustion, no difference was observed in peak oxygen uptake (&OV0312;o2peak), respiratory exchange ratio, HR, or RPE between 30-15IFT and CT. In contrast, 30-15IFT led to significantly higher minute ventilation, [La]peak, and final velocity than CT (p < 0.05 for all parameters). All maximal cardiorespiratory variables observed during both tests were moderately to well correlated (e.g., r = 0.76, p = 0.001 for &OV0312;o2peak). Regarding ventilatory thresholds (VThs), all cardiorespiratory measurements were similar and well correlated between the 2 tests. Parasympathetic function was lower after 30-15IFT than after CT, as indicated by significantly longer HHRtau (81.9 +/- 18.2 vs. 60.5 +/- 19.5 for 30-15IFT and CT, respectively, p < 0.001) and lower HRV vagal-related indices (i.e., the root mean square of successive R-R intervals differences [rMSSD]: 4.1 +/- 2.4 and 7.0 +/- 4.9 milliseconds, p < 0.05). In conclusion, the 30-15IFT is accurate for assessing VThs and &OV0312;o2peak, but it alters postexercise parasympathetic function more than a continuous incremental protocol.

Prospective pathways between heroin use and nonmedical use of prescription opioids: Trajectories among young Swiss men

BACKGROUND. So far few studies have focused on the last steps of drug-use trajectories. Heroin has been described as a final stage, but the non-medical use of prescription opioids (NMUPOs) is often associated with heroin use. There is, however, no consensus yet about which one precedes the other. AIMS. The objective of this study was to test which of these two substances was likely to be induced by the other using a prospective design. MATERIAL AND METHODS. We used data from the Swiss Longitudinal Cohort Study on Substance Use Risk Factors (C-SURF) to assess exposure to heroin and NMUPO at two times points (N = 5,041). Cross-lagged panel models provided evidence regarding prospective pathways between heroin and NMUPOs. Power analyses provided evidence about significance and clinical relevance. RESULTS. Results showed that heroin use predicted later NMUPO use (? = 1.217, p < 0.001) and that the reverse pathway was non-significant (? = 0.240, p = .233). Heroin use seems to be an important determinant, causing a 150% risk increase for NMUPO use at follow-up, whereas NMUPO use at baseline increases the risk of heroin use at follow-up by a mere non-significant 20%. CONCLUSIONS. Thus, heroin users were more likely to move to NMUPOs than non-heroin users, whereas NMUPO users were not likely to move to heroin use. The pathway of substance use seemed to include first heroin use, then NMUPO use.

Exercise efficiency relates with mitochondrial content and function in older adults.

Chronic aerobic exercise has been shown to increase exercise efficiency, thus allowing less energy expenditure for a similar amount of work. The extent to which skeletal muscle mitochondria play a role in this is not fully understood, particularly in an elderly population. The purpose of this study was to determine the relationship of exercise efficiency with mitochondrial content and function. We hypothesized that the greater the mitochondrial content and/or function, the greater would be the efficiencies. Thirty-eight sedentary (S, n = 23, 10F/13M) or athletic (A, n = 15, 6F/9M) older adults (66.8 ± 0.8 years) participated in this cross sectional study. V˙O2peak was measured with a cycle ergometer graded exercise protocol (GXT). Gross efficiency (GE, %) and net efficiency (NE, %) were estimated during a 1-h submaximal test (55% V˙O2peak). Delta efficiency (DE, %) was calculated from the GXT. Mitochondrial function was measured as ATPmax (mmol/L/s) during a PCr recovery protocol with (31)P-MR spectroscopy. Muscle biopsies were acquired for determination of mitochondrial volume density (MitoVd, %). Efficiencies were 17% (GE), 14% (NE), and 16% (DE) higher in A than S. MitoVD was 29% higher in A and ATPmax was 24% higher in A than in S. All efficiencies positively correlated with both ATPmax and MitoVd. Chronically trained older individuals had greater mitochondrial content and function, as well as greater exercise efficiencies. GE, NE, and DE were related to both mitochondrial content and function. This suggests a possible role of mitochondria in improving exercise efficiency in elderly athletic populations and allowing conservation of energy at moderate workloads.

Coronary vasomotor responses to isometric handgrip exercise are primarily mediated by nitric oxide: a noninvasive MRI test of coronary endothelial function.

Endothelial cell release of nitric oxide (NO) is a defining characteristic of nondiseased arteries, and abnormal endothelial NO release is both a marker of early atherosclerosis and a predictor of its progression and future events. Healthy coronaries respond to endothelial-dependent stressors with vasodilatation and increased coronary blood flow (CBF), but those with endothelial dysfunction respond with paradoxical vasoconstriction and reduced CBF. Recently, coronary MRI and isometric handgrip exercise (IHE) were reported to noninvasively quantify coronary endothelial function (CEF). However, it is not known whether the coronary response to IHE is actually mediated by NO and/or whether it is reproducible over weeks. To determine the contribution of NO, we studied the coronary response to IHE before and during infusion of N(G)-monomethyl-l-arginine (l-NMMA, 0.3 mg·kg(-1)·min(-1)), a NO-synthase inhibitor, in healthy volunteers. For reproducibility, we performed two MRI-IHE studies ∼8 wk apart in healthy subjects and patients with coronary artery disease (CAD). Changes from rest to IHE in coronary cross-sectional area (%CSA) and diastolic CBF (%CBF) were quantified. l-NMMA completely blocked normal coronary vasodilation during IHE [%CSA, 12.9 ± 2.5 (mean ± SE, placebo) vs. -0.3 ± 1.6% (l-NMMA); P < 0.001] and significantly blunted the increase in flow [%CBF, 47.7 ± 6.4 (placebo) vs. 10.6 ± 4.6% (l-NMMA); P < 0.001]. MRI-IHE measures obtained weeks apart strongly correlated for CSA (P < 0.0001) and CBF (P < 0.01). In conclusion, the normal human coronary vasoactive response to IHE is primarily mediated by NO. This noninvasive, reproducible MRI-IHE exam of NO-mediated CEF promises to be useful for studying CAD pathogenesis in low-risk populations and for evaluating translational strategies designed to alter CAD in patients.

Effects of exercise on mitochondrial DNA content in skeletal muscle of patients with COPD

Background Exhausting exercise reduces the mitochondrial DNA (mtDNA) content in the skeletal muscle of healthy subjects due to oxidative damage. Since patients with chronic obstructive pulmonary disease (COPD) suffer enhanced oxidative stress during exercise, it was hypothesised that the mtDNA content will be further reduced. Objective To investigate the effects of exercise above and below the lactate threshold (LT) on the mtDNA content of skeletal muscle of patients with COPD. Methods Eleven patients with COPD (676 8 years; forced expiratory volume in 1s (FEV1)456 8%ref) and 10 healthy controls (666 4 years; FEV1 906 7% ref) cycled 45 min above LT (65% peak oxygen uptake (V9O2 peak)and another 7 patients (656 6 years; FEV1 506 4%ref)and 7 controls (566 9 years;FEV1 926 6%ref) cycled 45 min below their LT (50% V9O2 peak). Biopsies from the vastus lateralis muscle were obtained before exercise, immediately after and 1 h, 1 day and 1 week later to determine by PCR the mtDNA/nuclear DNA (nDNA) ratio (a marker of mtDNA content) and the expression of the peroxisome proliferator-activated receptor- g coactivator-1 a (PGC-1a)mRNA and the amount of reactive oxygen species produced during exercise was estimated from total V9O2. Results Skeletal muscle mtDNA/nDNA fell significantly after exercise above the LT both in controls and in patients with COPD, but the changes were greater in those with COPD. These changes correlated with production of reactive oxygen species, increases in manganese superoxide dismutase and PGC-1 a mRNA and returned to baseline values 1 week later. This pattern of response wa was also observed, albeit minimised, in patients exercising below the LT. Conclusions In patients with COPD, exercise enhances the decrease in mtDNA content of skeletal muscle and the expression of PGC-1 a mRNA seen in healthy subjects probably due to oxidative stress.

Effect of aerobic exercise on skeletal muscle mitochondrial content and function in older adults

Regular aerobic exercise training, which is touted as a way to ameliorate metabolic diseases, increases aerobic capacity. Aerobic capacity usually declines with advanced age. The decline in aerobic capacity is typically associated by a decrease in the quality of skeletal muscle. At the molecular level, this decreased quality comes in part from perturbations in skeletal muscle mitochondria. Of particular is a decrease in the total amount of mitochondria that occupy the skeletal muscle volume. What is not well established is if this decrease in mitochondrial content is due to inactive lifestyle or the process of aging. Herein, the work of the thesis shows a clear connection between mitochondrial content and aerobic capacity. This indicates that active individuals with higher VChmax levels also contain higher volumes of mitochondria inside their muscle as opposed to sedentary counterparts who have lower levels of mitochondrial content. Upon taking these previously sedentary individuals and entering them into an aerobic exercise intervention, they are able to recover their mitochondrial content as well as function to similar levels of lifelong athletes of the same age. Furthermore, the results of this thesis show that mitochondrial content and function also correlate with exercise efficiency. If one is more efficient, he/she is able to expend less energy for a similar power output. Furthermore, individuals who increase in efficiency also increase in the ability to oxidize and utilize fat during pro-longed exercise. This increased reliance on fat after the intervention is associated with an increased amount of mitochondria, particularly in the intermyofibrillar region of skeletal muscle. Therefore, elderly adults who were once sedentary were able to recover mitochondrial content and function and are able to reap other health benefits from regular aerobic exercise training. Aging per se does not seem to be the culprit that will lead to metabolic diseases but rather it seems to be a lack of physical activity. -- Un entraînement sportif d'endurance, connu pour réduire le risque de développer des maladies métaboliques, augmente notre capacité aérobie. La capacité aérobie diminue généralement avec l'âge. Ce déclin est typiquement associé d'une diminution de la qualité du muscle squelettique. Au niveau moléculaire, cette diminution est due à des perturbations dans les mitochondries du muscle squelettique,, ce qui conduit à une diminution de la quantité totale des mitochondries présentes dans le muscle squelettique. Il n'a pas encore été établi si cette diminution de la teneur mitochondriale est due à un mode de vie sédentaire ou au processus du vieillissement. Ce travail de thèse montre un lien clair entre le contenu mitochondrial et la capacité aérobie. Il indique que des personnes âgées actives, avec des niveaux de V02max plus élevés, possèdent également un volume plus élevé de mitochondries dans leurs muscles en comparaison à leurs homologues sédentaires. En prenant des individus sédentaires et leur faisant pratiquer une activité physique aérobie, il est possible d'accroître leur contenu de même que leur fonction mitochondriale à des niveaux similaires à ceux d'athlètes du même âge ayant pratiqué une activité physique tout au long de leur vie. De plus, les résultats de ce travail démontrent que le contenu et la fonction mitochondriale sont en corrélation avec l'efficiscience lors d'exercice physique. En agumentant l'effiscience, les personnes sont alors capables de dépenser moins d'énergie pour une puissance d'exercice similaire. Donc, un volume mitochondrial accru dans le muscle squelettique, associé à une fonction mitochondriale améliorée, est associté à une augmentation de l'effiscience. En outre, les personnes qui augmentent leur effiscience, augmentent aussi leur capacité à oxyder les graisses durant l'exercice prolongé. Une augmentation du recours au graisses après l'intervention est associée à une quantité accrue de mitochondries, en particulier dans la région inter-myofibrillaire du muscle squelettique. Par conséquent, les personnes âgées autrefois sédentaires sont en mesure de récupérer leur contenu et leur fonction mitochondriale ainsi que d'autres avantages pour la santé grâce à un entraînement aérobie régulier. Le vieillissement en soi ne semble donc pas être le coupable conduisant aux maladies métaboliques qui semblent plutôt être lié à un manque d'activité physique.

Effects of Three Types of Exercise Interventions on Healthy Old Adults' Gait Speed : A Systematic Review and Meta-Analysis.

BACKGROUND: Habitual walking speed predicts many clinical conditions later in life, but it declines with age. However, which particular exercise intervention can minimize the age-related gait speed loss is unclear. PURPOSE: Our objective was to determine the effects of strength, power, coordination, and multimodal exercise training on healthy old adults' habitual and fast gait speed. METHODS: We performed a computerized systematic literature search in PubMed and Web of Knowledge from January 1984 up to December 2014. Search terms included 'Resistance training', 'power training', 'coordination training', 'multimodal training', and 'gait speed (outcome term). Inclusion criteria were articles available in full text, publication period over past 30 years, human species, journal articles, clinical trials, randomized controlled trials, English as publication language, and subject age ≥65 years. The methodological quality of all eligible intervention studies was assessed using the Physiotherapy Evidence Database (PEDro) scale. We computed weighted average standardized mean differences of the intervention-induced adaptations in gait speed using a random-effects model and tested for overall and individual intervention effects relative to no-exercise controls. RESULTS: A total of 42 studies (mean PEDro score of 5.0 ± 1.2) were included in the analyses (2495 healthy old adults; age 74.2 years [64.4-82.7]; body mass 69.9 ± 4.9 kg, height 1.64 ± 0.05 m, body mass index 26.4 ± 1.9 kg/m(2), and gait speed 1.22 ± 0.18 m/s). The search identified only one power training study, therefore the subsequent analyses focused only on the effects of resistance, coordination, and multimodal training on gait speed. The three types of intervention improved gait speed in the three experimental groups combined (n = 1297) by 0.10 m/s (±0.12) or 8.4 % (±9.7), with a large effect size (ES) of 0.84. Resistance (24 studies; n = 613; 0.11 m/s; 9.3 %; ES: 0.84), coordination (eight studies, n = 198; 0.09 m/s; 7.6 %; ES: 0.76), and multimodal training (19 studies; n = 486; 0.09 m/s; 8.4 %, ES: 0.86) increased gait speed statistically and similarly. CONCLUSIONS: Commonly used exercise interventions can functionally and clinically increase habitual and fast gait speed and help slow the loss of gait speed or delay its onset.