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Biomedical subjects

M Francaux

Publications and source records attributed to M Francaux.

At least 19 recordsLinked to original sources

Regulation of mTOR by amino acids and resistance exercise in skeletal muscle.

Resistance exercise disturbs skeletal muscle homeostasis leading to activation of catabolic and anabolic processes within the muscle cell. A current challenge of exercise biology is to describe the molecular mechanisms of regulation by which contractile activity stimulates net protein breakdown during exercise and net protein synthesis during recovery. Muscle growth is optimized by combining exercise and appropriate nutritional strategies, such as amino acid (AA) and carbohydrate ingestion. The effects are integrated at the level of one central regulatory protein, mTOR (mammalian target of rapamycin). mTOR is a complex protein integrating signals of the energetic status of the cell and environmental stimuli to control protein synthesis, protein breakdown and therefore cell growth. mTOR is known to be activated by insulin, and the mechanisms involved are well documented. The ways by which exercise and AA lead to mTOR activation remain partially unclear. Exercise and AA use different signalling pathways upstream of mTOR. Exercise seems to recruit partially the same pathway as insulin, whereas AA could act more directly on mTOR. During resistance exercise, the activity of mTOR could be acutely blunted by AMP-activated protein kinase (AMPK), thus inhibiting protein synthesis and enhancing AA availability for energy metabolism. During recovery, the inhibition of mTOR by AMPK is suppressed, and its activation is maximized by the presence of AA. There appears to be a requirement for a minimal concentration of plasma insulin to stimulate muscle protein synthesis in response to resistance exercise and AA ingestion.

Adaptation, Physiological↗

Changes in plasma and urinary taurine and amino acids in runners immediately and 24h after a marathon.

Changes in urinary and plasma taurine and amino acids have been evaluated in trained runners competing in the Rotterdam Marathon, 1998, both immediately after completing the event and 24h after recovery. There were significant changes in the urinary amino acids excretion, the majority showing a significant decrease both immediately at the completion of the Marathon and after 24h recovery. In contrast urinary taurine excretion increased immediately post Marathon, although not significantly as the range of results was wide. Such changes in urinary taurine correlated with percentage changes in plasma creatine kinase both immediately post race, (r = 0.972, P < 0.001), and 24h later (r = 0.872, P < 0.001), possibly indicating that the source of the taurine was muscle. Significant correlations between the individual values for urinary and plasma amino acids in all of the athletes were calculated for taurine (r = 0.528), glycine (r = 0.853), threonine (r = 0.749), alanine (r = 0.747), serine (r = 0.620), glutamine (0.614), arginine (r = 0.507), histidine (r = 0.470) and valine (r = 0.486). Changes in the mean plasma concentrations of amino acids were comparable to our previously published data (Ward et al., 1999) the majority showing significant decreases immediately and 24h post Marathon, such an adaptation being due primarily to their utilisation for gluconeogenesis. However, in contrast, the mean taurine concentrations were significantly elevated both post race, P < 0.01 and after 24h, P < 0.05. The physiological response by the muscle to exhaustive exercise, particularly with regard to changes in plasma and urinary taurine concentrations remain to be elucidated, but is probably related to muscle function impairment. The increase in taurine urinary excretion could be used as an indicator of muscle damage occurring during exhaustive exercise. Whether taurine supplementation would minimise such changes is an interesting scientific question and merits investigation.

Amino Acids↗

Cutaneous vascular response and thermoregulation in individuals with paraplegia during sustained arm-cranking exercise.

This study investigated whether a 60-minute arm-cranking exercise at 50% of the individual maximal power output would increase lower limb skin blood flow (laser Doppler flowmetry) in individuals with high-level (T5-T9; n = 6) and low-level paraplegia (T10-T12; n = 6), compared to 6 able-bodied controls. Significant (P < 0.05) group by time interactions (two-way repeated measures ANOVA) were found for leg cutaneous vascular conductance, leg skin temperature and esophageal temperature. Cutaneous vascular conductance increased to a peak of approximately 180% of pre-exercise rest in both paraplegic groups and to -436% in the control group, with differences after 15, 30, 45 and 60 minutes of exercise. Leg skin temperature increased by approximately 0.3 C in individuals with paraplegia and decreased by approximately 2.0 C in able-bodied. Esophageal temperature increases at the end of exercise were higher in individuals with paraplegia (approximately 0.9 C) than in able-bodied subjects (approximately 0.5 C). Heart rate was higher in the paraplegic groups than in able-bodied, whilst stroke volume and cardiac output were not different (impedance cardiography). The data suggest that lesion level had no influence on the results. These findings indicate that there is no excessive shunting of blood to the skin of the lower limbs of individuals with paraplegia during sustained exercise.

Adult↗

Central and peripheral haemodynamics in individuals with paraplegia during light and heavy exercise.

The purpose of this study was to analyse lower leg skin blood flow (laser Doppler flowmetry) in five individuals with high-level paraplegia (T5-T9), six participants with low-level paraplegia (T10-T12) and six able-bodied controls during 3-minute light and heavy arm-cranking exercises (approximately 15% and 80% peak power output, respectively). Throughout light exercise, cutaneous vasoconstriction was shown for the control group (-20%), but not the low-level (+62%) or the high-level paraplegic group (+33%). During heavy exercise, vasoconstriction was initially found for controls followed by an increase in skin blood flow during the last 2 minutes, whereas the participants with paraplegia demonstrated skin blood flow increases. Skin blood flow responses were not related to lesion level. Metabolic parameters were not different among the three groups, but heart rates for participants with paraplegia were higher during heavy exercise than in controls. These results suggest impaired sympathetic vasoconstriction in individuals with paraplegia during exercise.

Adult↗

Effects of guandinoethane sulfonate on contraction of skeletal muscle.

Guanidinoethane sulfonic acid (GES), a chemical and biological analog of taurine, decreases rat muscle taurine content when added to drinking water. Over the same period, GES appears in muscle. GES supplementation is often used to study the effect of taurine depletion on physiological mechanisms, without taking into account the possible actions of GES. The purpose of the present study was to investigate the specific actions of GES on contraction of skeletal muscle. In mice EDL muscle, the time delay needed to observe a 20% force decrease after the end of a tetanic stimulation was higher in GES-supplemented than in control muscle. This observation in GES-supplemented muscle could be explained by the action of taurine or GES on several targets, beside others the rate of Ca2+ uptake by sarcoplasmic reticulum (SR) and the Ca2+ sensitivity of myofilaments. SR of rat EDL was isolated by successive centrifugations. The effect of 20 mM taurine or GES on the rate of Ca2+ uptake by SR was measured with the fluorescent Ca2+ indicator fura-2. The results show that the rate of Ca2+ uptake by SR is not modified in the presence of taurine or GES. The Ca2+ sensitivity of myofilaments was studied in chemically skinned fibers in the presence of 20 mM taurine or GES. Both taurine and GES increased the myofilament sensitivity to Ca2+. Thus, the prolonged relaxation time of GES-supplemented muscle can be attributed to an increase in myofilament sensitivity to Ca2+. This higher sensitivity is not due to a decrease in muscle taurine content but rather to an increased GES concentration.

Actin Cytoskeleton↗

Cutaneous vasomotor adjustments during arm-cranking in individuals with paraplegia.

difference, P<0.05). The paraplegics developed a higher esophageal and leg skin temperature, which was attributed to the lack of active vasodilation and evaporative cooling over the legs. The results indicate that individuals with paraplegia suffer from impaired cutaneous vasoconstriction at the onset of arm exercise, and possess only a limited vasodilatory capability in the paralyzed regions. During intense exercise, thermoregulation depends critically on active cutaneous vasodilation and skin cooling.

Adult↗

Blood distribution adaptations in paraplegics during posture changes: peripheral and central reflex responses.

The veno-arteriolar reflex (VAR) in spinal-cord-injured subjects (SCI) has been attributed little interest, although it might contribute substantially to their blood redistribution. This peripheral reflex response, which is based on an axon reflex, consists of a reduction in limb blood flow following an increase in venal transmural pressure. The purpose of the present investigation was to assess the peripheral and central cardiovascular adaptations of paraplegics with high (HP) and low (LP) spinal lesions to subsequent, passive posture changes involving leg dependency and upright sitting, and to compare them to able-bodied (AB) subjects. Lower-limb cutaneous vascular conductance (CVC) was evaluated from skin blood flow measurements (laser Doppler flowmetry) taken from the dorsal foot, and from ankle blood pressure. Cardiac stroke volume, heart rate and myocardial performance were assessed using impedance cardiography and brachial blood pressure. During leg dependency, a significant vasoconstriction was noted in all three groups. The initial decrease in CVC was higher in HP (-76.82%) than in AB (-45.82%), the values for LP (-67.08%) lying in between these two (significant group x time interaction: F = 2.832; P = 0.042). There were no differences for parameters of central hemodynamics. No between-group differences were noted in any parameter tested during upright sitting. CVC remained at a similar low level as compared to leg dependency, stroke volume decreased, heart rate and blood pressure increased, and myocardial performance remained constant. The present results suggest that paraplegics have a peripheral VAR in their paralyzed lower limbs, and that this contributes to their cardiovascular stability.

Adaptation, Physiological↗

Effect of exogenous creatine supplementation on muscle PCr metabolism.

31P NMR was used to assess the influence of two weeks creatine supplementation (21g x d(-1)) on resting muscle PCr concentration, on the rate of PCr repletion (R(depl)), and on the half-time of PCr repletion (t 1/2). Body mass (BM) and volume of body water compartments were also estimated by impedance spectroscopy. Fourteen healthy male subjects (20.8+/-1.9 y) participated in this double-blind study. PCr was measured using a surface coil placed under the calf muscle, at rest and during two exercise bout the duration of which was 1 min. They were interspaced by a recovery of 10 min. The exercises comprised of 50 plantar flexions-extensions against weights corresponding to 40% and 70% of maximal voluntary contraction (MVC), respectively. Creatine supplementation increased resting muscle PCr content by approximately 20% (P= 0.002). R(depl) was also increased by approximately 15% (P< 0.001) and approximately 10% (P = 0.026) during 40% and 70% MVC exercises, respectively. No change was observed in R(repl) and t1/2. BM and body water compartments were not influenced. These results indicate that during a standardized exercise more ATP is synthesized by the CK reaction when the pre-exercise level in PCr is higher, giving some support to the positive effects recorded on muscle performance.

Adenosine Triphosphate↗

Adverse effects of creatine supplementation: fact or fiction?

The consumption of oral creatine monohydrate has become increasingly common among professional and amateur athletes. Despite numerous publications on the ergogenic effects of this naturally occurring substance, there is little information on the possible adverse effects of this supplement. The objectives of this review are to identify the scientific facts and contrast them with reports in the news media, which have repeatedly emphasised the health risks of creatine supplementation and do not hesitate to draw broad conclusions from individual case reports. Exogenous creatine supplements are often consumed by athletes in amounts of up to 20 g/day for a few days, followed by 1 to 10 g/day for weeks, months and even years. Usually, consumers do not report any adverse effects, but body mass increases. There are few reports that creatine supplementation has protective effects in heart, muscle and neurological diseases. Gastrointestinal disturbances and muscle cramps have been reported occasionally in healthy individuals, but the effects are anecdotal. Liver and kidney dysfunction have also been suggested on the basis of small changes in markers of organ function and of occasional case reports, but well controlled studies on the adverse effects of exogenous creatine supplementation are almost nonexistent. We have investigated liver changes during medium term (4 weeks) creatine supplementation in young athletes. None showed any evidence of dysfunction on the basis of serum enzymes and urea production. Short term (5 days), medium term (9 weeks) and long term (up to 5 years) oral creatine supplementation has been studied in small cohorts of athletes whose kidney function was monitored by clearance methods and urine protein excretion rate. We did not find any adverse effects on renal function. The present review is not intended to reach conclusions on the effect of creatine supplementation on sport performance, but we believe that there is no evidence for deleterious effects in healthy individuals. Nevertheless, idiosyncratic effects may occur when large amounts of an exogenous substance containing an amino group are consumed, with the consequent increased load on the liver and kidneys. Regular monitoring is compulsory to avoid any abnormal reactions during oral creatine supplementation.

Administration, Oral↗

Changes in plasma taurine levels after different endurance events.

The sulphonated amino acid taurine increased significantly in the plasma of trained athletes after three endurance exercises of different duration and intensity, a 90 min run on a treadmill at 75% of an individual's VO2 peak, a Marathon, 42.2 km and a 100 km run, by 19%, 77% and 36%, respectively. Such results indicated that the speed at which the exercise is performed, referred to as the intensity, rather than the duration of the exercise, correlated with the elevated taurine levels possibly indicating its release from muscle fibres. The plasma amino acid pool decreased significantly in relationship with the duration of the exercise, caused by their utilisation for glucogenesis. The possible sources of the increased plasma taurine are discussed.

Adult↗

Effects of training and creatine supplement on muscle strength and body mass.

The purpose of this study was to test the effect of creatine supplement on the size of the extra- and intracellular compartments and on the increase of isokinetic force during a strength training-program. Twenty-five healthy male subjects (age 22.0+/-2.9 years) participated in this experiment. Seven subjects formed the control-group. They did not complete any training and did not have any dietary supplement. The eighteen other subjects were randomly divided into a creatine- (n = 8) and a placebo-group (n = 10). They were submitted to a controlled strength-training program for 42 days followed by a detraining period of 21 days. Creatine and placebo were given over a period of 9 weeks. The size of the body water compartments was assessed by bioimpedance spectroscopy and the isokinetic force was determined during a single squat by means of an isokinetic dynamometer. These measurements were completed beforehand, at the end of the training period, and after the determining period. Both placebo- and creatine-group increased the isokinetic force by about 6% after the training period, showing that creatine ingestion does not induce a higher increase of the force measured during a single movement. No change in body mass was observed in the control- and placebo-groups during the entire experiment period while the body mass of the creatine-group was increased by 2 kg (P < 0.001). This change can be attributed partially to an increase (P = 0.039) in the body water content (+1.11), and more specifically, to an increase (P < 0.001) in the volume of the inter-cellular compartment (+0.61). Nevertheless, the relative volumes of the body water compartments remained constant and therefore the gain in body mass cannot be attributed to water retention, but probably to dry matter growth accompanied with a normal water volume.

Adult↗

Long-term oral creatine supplementation does not impair renal function in healthy athletes.

PURPOSE: Oral creatine supplementation is widely used in sportsmen and women. Side effects have been postulated, but no thorough investigations have been conducted to support these assertions. It is important to know whether long-term oral creatine supplementation has any detrimental effects on kidney function in healthy population. METHODS: Creatinine, urea, and plasma albumin clearances have been determined in oral creatine consumers (10 months to 5 yr) and in a control group. RESULTS: There were no statistical differences between the control group and the creatine consumer group for plasma contents and urine excretion rates for creatinine, urea, and albumin. Clearance of these compounds did not differ between the two groups. Thus, glomerular filtration rate, tubular reabsorption, and glomerular membrane permeability were normal in both groups. CONCLUSIONS: Neither short-term, medium-term, nor long-term oral creatine supplements induce detrimental effects on the kidney of healthy individuals.

Absorption↗

Impedance cardiography applied to maximal arm cranking exercise: a matter of sampling and processing strategy.

PURPOSE: A new ensemble-averaging (EA) approach was developed with the goal of investigating central hemodynamics by transthoracic impedance cardiography during maximal arm cranking. This EA procedure of the first time derivative of impedance changes (dZ/dt) over several cardiac cycles differs from previously reported techniques with respect to cycle selection strategy, according to fixed criteria, and processing methods. METHODS: First, the primary elements of the Kubicek stroke volume (SV) formula, as determined by EA, were compared with the values determined by the standard hand-processing (HP) method over a large range of cardiac outputs. RESULTS: Results showed a very high reliability for ventricular ejection time (r = 0.996), (dZ/dt)min (r = 0.995), SV (r = 0.977), and heart rate (r = 0.999). Second, the EA procedure was applied to six subjects performing a continuous, multistage arm cranking test to volitional fatigue. The present technique allowed for an effective filtering of movement and breathing artifacts of the original signal. Thus, interpretation of the dZ/dt wave form was convenient, even at maximal arm cranking power outputs up to 120 W. Stroke volume ranged from 63.83 to 127.18 mL.beat-1, showing no significant variations with oxygen consumption. Cardiac output increased linearly with oxygen uptake, reaching a mean maximal value of 16 L.min-1. CONCLUSION: The present procedure opens a new field of application to impedance cardiography, permitting to measure cardiac output during maximal arm cranking exercise.

Adult↗

31P NMR saturation transfer study of the creatine kinase reaction in human skeletal muscle at rest and during exercise.

The creatine kinase reaction has been studied by 31P NMR in exercising human calf muscle. Quantitative analysis of high energy phosphates and saturation transfer study of the creatine kinase flux in the direction of ATP synthesis (Vfor) were performed at rest and during exercise. As expected, exercise induced a [PCr] decrease (from 28.5 +/- 0.9 to 21.9 +/- 1.5 mM, P < 0.01) matched by a Pi increase (from 4.5 +/- 0.2 to 8.9 +/- 1.8 mM, P = 0.06). pHi and [ATP] remained unchanged. Vfor did not change from rest (12.4 +/- 0.9 mM s(-1)) to moderate exercise and decreased at the highest exercise level (8.4 +/- 1.4 mM s(-1), P = 0.006). This observation differs from the prediction of the creatine kinase rate equation, showing an increase in the flux with exercise intensity. Computations suggest that this discrepancy arises from metabolite compartmentalization and/or from the reaction kinetics of a dead end complex stabilized by planar anions.

Adult↗

Measurement of the power output during the acceleration phase of all-out arm cranking exercise.

The purpose of this study was to develop an original friction loaded ergometer allowing measurement of the resisting torque (Mb) and the angular velocity (omega) by means of a force transducer and an optical pick-up during all-out arm cranking exercises. Taking into account the kinetic energy variations of the flywheel, the peak power developed at the crank (P(c)peak) and the peak angular velocity (omegapeak) were determined in 6 male and 6 female able-bodied subjects during 6-8 bouts of 3 s duration, performed at maximal velocity, with Mb varying from 0.07 to 0.87 Nm x kg(-1). In each subject, the Mb increase was related to a decrease of omegapeak. This relationship was expressed through a negative linear regression (0.92 < R2 < 0.99) for omegapeak between 13 and 28 rad x s(-1) for the males and 10 and 24 rad x s(-1) for the females. The relationship between P(c)peak and Mb did not fit well for all subjects (0.01 < R2 < 0.93) with a parabolic equation, indicating that for upper limb testing, the maximal power should be defined as the highest power measured during several bouts performed with appropriate resisting torque. The present study also demonstrated the importance of taking into account the inertia of the moving flywheel during the acceleration phase of an all-out arm crank exercise, when determining the peak power output.

Acceleration↗

Free magnesium concentration in isolated rabbit hearts subjected to high dose isoproterenol infusion: a 31P NMR study.

The hypothesis of magnesium deficiency in isoproterenol (ISO) induced myocardial injury has been investigated by 31P nuclear magnetic resonance spectroscopy. High energy phosphate concentrations, pHi, and intracellular free magnesium concentration ([Mg2+]i) were measured in isolated rabbit hearts perfused at constant flow and subjected to 10(-6)M isoproterenol during 30 min. Recent calibrations were used for [Mg2+]i measurements, and uncertainties on [Mg2+]i estimated values were calculated. During isoproterenol infusion, pHi, [PCr], and [ATP] decreased, while [P(i)] increased. When it was stopped, [PCr] completely repleted, whereas only a partial restoration was observed for pHi and [P(i)]. A rise of end-diastolic pressure and perfusion pressure expressed a contracture, concomitant with a lack of [ATP] recovery, which remained at 59 +/- 13% of the rest value. These results establish that 10(-6) M isoproterenol caused severe myocardial injury. [Mg2+]i increased from 0.70 mM at rest to 0.88 mM at the end of the isoproterenol period. Considering the estimated uncertainties on the [Mg2+]i values, this increase was not significant. After isoproterenol infusion, [Mg2+]i progressively decreased to reach 0.72 mM at 45 min recovery. It is concluded that isoproterenol myocardial toxicity may not be related to [Mg2+]i deficiency.

Adenosine Triphosphate↗