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Biomedical subjects

G Dupont

Publications and source records attributed to G Dupont.

At least 19 recordsLinked to original sources

Performance and muscle oxygenation during isometric exercise and recovery in children with congenital heart diseases.

This study investigated performance, muscle oxygen saturation (StO2), and blood volume (BV) in patients with congenital heart diseases (CHD) and healthy children during and following sustained exercise. Maximal volunteered contraction (MVC) and endurance at 50 % of MVC (time to exhaustion, Tlim) of the knee extensor were measured in nine patients with CHD and 14 healthy control children. Near infrared spectroscopy was used to evaluated StO2 and BV in vastus lateralis. The drop in muscle oxygen saturation (D(mO2)), half time of recovery (T(SR)), and recovery speed to maximal oxygen saturation (Rs) were analyzed. Patients with CHD showed lower MVC (101.0 +/- 6.2 vs. 125.5 +/- 7.4 N x m, p < 0.01) and Tlim (67.0 +/- 7.5 vs. 127.5 +/- 11.1 s, p < 0.001) than control children. StO2 and BV values in both groups were similar at rest and decreased at the onset of contraction. D(mO2) was larger in patients, which reflected pronounced deoxygenation. During recovery, the patients exhibited a longer TSR (25.2 +/- 2.1 vs. 18.4 +/- 2.0 s, p < 0.05) and R(S) (64.6 +/- 5.5 vs. 42.7 +/- 4.6 s, p < 0.01) than control children. We concluded that reduced strength and endurance in patients with CHD were associated with an impairment of StO2 and BV, and a slower reoxygenation during recovery.

Adolescent↗

Respiratory muscle deoxygenation and ventilatory threshold assessments using near infrared spectroscopy in children.

The aim of this study was to assess respiratory muscles deoxygenation and to determine ventilatory threshold using near infrared spectroscopy (NIRS) in children during incremental cardiopulmonary exercise. Fourteen healthy children with a mean +/- SD age of 12.8 +/- 1.4 yrs performed an incremental exercise test on a cycle ergometer. NIRS was used to assess deoxygenation of the respiratory muscles. Ventilatory parameters (oxygen uptake, carbon dioxide production, and ventilation minute), power output, and tissue saturation (StO2) were measured. Ventilatory threshold was determined by the two following methods: the V-slope method which corresponds to the breakpoint in VCO2 as a function VO2 relationship (VT(V-slope)) and the NIRS method which corresponds to the point of rapid fall in StO2 (VT(nirs)). During exercise, the respiratory muscles deoxygenated as the exercise intensity increased. StO2 decrease progressively until an abrupt decrease was observed. No significant differences were observed between cardiorespiratory variables corresponding either to VT(V-slope) or to VT(nirs). The two methods showed a good agreement (data were inside the 95 % confidence interval). Likewise, a significant relationship was found between VT(V-slope) and VT(nirs) for each parameter measured (r = 0.87 to 0.94, p < 0.001). We concluded that respiratory muscles deoxygenate during incremental exercise in children and that ventilatory threshold could be determined by NIRS.

Anaerobic Threshold↗

Development of 400 microm pellets by extrusion-spheronization: application with Gelucire 50/02 to produce a "sprinkle" form.

The aim of this study was to develop monodimensional, spherical particles of 400 microm by extrusion-spheronization. An Alexanderwerk GA65 cylinder extruder with two counter-rotating rollers associated with a Caleva model 15 spheronizer were used. The study was made with an auxiliary substance of fatty consistency and with amphiphilic properties: Gelucire 50/02. The plasticity of the mass can be deduced using a piston extruder. Pellet quality can be determined by particle-size analysis and shape estimation by microscopy. Modifications to the cylinders and the extruder itself are required for feasibility studies of extruded materials of 400 microm. The horizontal plate of the spheronizer had to be adapted to take into account the small size of the extruded materials. For the chosen auxiliary substance, Gelucire 50/02, the formulation of the wet mass to be extruded and the conditions required to obtain this mass were defined. The results show the feasibility of 400 microm pellets with Gelucire 50/02. At least 90% of the pellets have a particle size of between 250 microm and 500 microm and particle shape is acceptable. In this form the dose can be adapted to individual patients. After proving the feasibility of 400 microm spheroids of Gelucire 50/02, the association of a drug with it was considered.

Drug Compounding↗

Ca2+ oscillations in hepatocytes do not require the modulation of InsP3 3-kinase activity by Ca2+.

Receptor-mediated production of inositol 1,4,5-trisphosphate (InsP(3)) initiates Ca(2+) release and is responsible for cytosolic Ca(2+) oscillations. InsP(3) oscillations have also been observed in some cells. One of the enzymes controlling InsP(3) catabolism, the InsP(3) 3-kinase, is stimulated by Ca(2+); this regulation is presumably part of the reason for InsP(3) oscillations that have been observed in some cells. Here, we investigate the possible role of Ca(2+)-activated InsP(3) catabolism on the characteristics of the InsP(3)-induced Ca(2+) oscillations. Numerical simulations show that if it is assumed that the Ca(2+)-independent InsP(3) catabolism is predominant, Ca(2+) oscillations remain qualitatively unchanged although the relative amplitude of the oscillations in InsP(3) concentrations becomes minimal. We tested this prediction in hepatocytes by masking the Ca(2+)-dependent InsP(3) catabolism by 3-kinase through the injection of massive amounts of InsP(3) 5-phosphatase, which is not stimulated by Ca(2+). We find that in such injected hepatocytes, Ca(2+) oscillations generated by modest agonist levels are suppressed, presumably because of the decreased dose in InsP(3), but that at higher doses of agonist, oscillations reappear, with characteristics similar to those of untreated cells at low agonist doses. Altogether, these results suggest that oscillations in InsP(3) concentration due to Ca(2+)-stimulated InsP(3) catabolism do not play a major role for the oscillations in Ca(2+) concentration.

Animals↗

Time spent at VO2max: a methodological issue.

This study was designed to propose a standardised procedure to determine the time spent at VO2max (tVO2max) based on the VO2max of the day (i. e. the VO2max value measured the day of the test). Ten male subjects first performed a graded field test, followed by a continuous running exercise to exhaustion, at the velocity of the Université de Montréal Track Test (V(UMTT)) plus 1 km x h(-1) (V(UMTT)(+1)). The second test consisted of an exhaustive run at 100 % of V(UMTT), followed by a V(UMTT)(+1) test. Different methods were used to compare time spent at VO2max, based on the VO2max of the graded field test, and time spent at VO2max, based on the VO2max of the day, during an exhaustive run at 100 % of V(UMTT). Results have shown that V(UMTT)(+1) tests were of sufficient intensity and duration to identify the VO2max of the day. Time spent at VO2max ranged from 25 +/- 53 s to 139 +/- 76 s according to the method used. However, the tVO2max method based on the sum of each value higher than 95 % of VO2max of the day appeared more robust than methods based on the time to exhaustion minus time to reach VO2 reference value, or the method based on the sum of values higher than VO2max minus 2.1 ml x kg(-1) x min(-1).

Adult↗

Plasma lactate and plasma volume recovery in adults and children following high-intensity exercises.

AIM: To compare plasma lactate concentration recovery kinetics when measured and corrected for variations in plasma volume between children and adults. METHODS: Nine boys (11.3 +/- 1.1 y) and 8 men (21.9 +/- 1.9 y) performed a maximal and a supramaximal exercise until exhaustion. Plasma lactate concentrations, haemoglobin and haematocrit were measured at rest, immediately on completion of exercise and after the 2nd, 5th, 12th and 30th minute of recovery. The plasma lactate concentrations and the rate of recovery were corrected for variations in plasma volume. RESULTS: The maximal decreases in plasma volume were significantly higher in adults than in children for maximal exercise (-18.7 +/- 2.6% vs -14.5 +/- 3.2%; p < 0.05), but similar for the supramaximal exercise (-16.9 +/- 3.4% vs -15.2 +/- 3.4%). During recovery, measured and corrected plasma lactate concentrations were significantly higher in adults. The rate of plasma lactate recovery was higher in adults for maximal exercise only. The same results were obtained when the rates of plasma lactate decrease were calculated from corrected plasma lactate concentrations. CONCLUSION: The correction of the plasma lactate concentrations for variations in plasma volume did not influence the comparison of the concentrations obtained in adults and children, or their rate of recovery.

Adult↗

Developing a study method for producing 400 microm spheroids.

The aim of this work was to obtain 400 microm spheroids that can be sprinkled on food to improve patient compliance particularly in the case of children and old people. A methodology to select wet masses for extrusion-spheronization through a 400 microm orifice was developed. The first step was to define the parameters that make it possible to assess the qualities required by the wet mass and the extrudates and evaluation norms: plasticity, cohesiveness, brittleness of the mass and the extrudates, and appearance of extrudates. A feasibility assay was then performed on the cylinder extruder, showing that extrusion of the lactose/Avicel PH 101/water (50/50/60) mass is not feasible through the 400 microm orifice. Precirol ato 5 and Gelucire 50/02 wetted with a sodium lauryl sulfate solution at 0.5% show plastic flow through the 400 microm diameter orifice. The presence of Avicel PH 101 does not improve plasticity for this orifice. Micropellets of 400 microm have been proved feasible as long as excipients with suitable pharmaceutical technological properties are used. After proving the feasibility of 400 microm spheroids of Gelucire 50/02, we considered the association of a drug with it.

Cellulose↗

Effects of high intensity intermittent training on peak VO(2) in prepubertal children.

This study was designed to examine peak VO(2) responses of prepubescent children following a 7-week aerobic training. Twenty-three boys and thirty girls (9.7 +/- 0.8 years) were divided into a high intensity experimental group (HIEG: 20 girls and 13 boys) and a control group (CG: 10 girls and 10 boys). A graded 20-m shuttle run with measurement of gas exchange values was performed prior to and after the 7-week training program. The test consisted of a 3-min run at 7 km x h(-1) to determine energy cost of running, immediately followed by a 20-meter shuttle run test. HIEG had two 30 min-sessions of short intermittent aerobic training per week at velocities ranging from 100 up to 130 % of the maximal aerobic speed. For HIEG, absolute peak VO(2)(9.1 %) and relative to body mass peak VO(2)(8.2 %) increased significantly (p < 0.001); it was unchanged in the CG. Similarly, maximal shuttle run improved significantly in HIEG (5.1 %, p < 0.001). In contrast, there was no significant change for CG. For both groups energy cost of running remained unchanged. These findings show that prepubescent children could significantly increase their peak VO(2) and maximal shuttle velocity with high intensity short intermittent aerobic exercises.

Age Factors↗

Effects of two low-dose oral contraceptives containing ethinylestradiol and either desogestrel or levonorgestrel on serum lipids and lipoproteins with particular regard to LDL size.

This study was designed to determine the effects of two low-dose oral contraceptives, most frequently given in our area, monophasic desogestrel/ethinylestradiol (DG/EE) and triphasic levonorgestrel/ethinylestradiol (LNG/EE), on lipoprotein parameters, especially LDL particle size and HDL subclass distribution (determined by lipid-stained 2%-20% polyacrylamide gradient gel electrophoresis) in 37 healthy normolipidemic women aged 19 to 27 years. Lipid and lipoprotein parameters were measured before the start of treatment and in the third month of oral contraceptive use. Results reflected the estrogen-progestin balance. As compared with baseline values, with both formulations, plasma total cholesterol, phospholipids, and HDL3 cholesterol increased, and LDL-predominant peak size decreased, with a translation of LDL pattern A towards pattern I. With DG/EE, plasma triglycerides, apolipoproteins AI and B increased. With LNG/EE, LDL cholesterol increased, and HDL2 cholesterol decreased. All these modifications were moderate, within threshold limits. Estrogen-dominant monophasic DG/EE appears to be more favorable than progestin-dominant triphasic LNG/EE, since the reduction in LDL-predominant peak size is not associated with an increase in LDL cholesterol or with a decrease in HDL2 cholesterol.

Adult↗

Investigation of the roles of Ca(2+) and InsP(3) diffusion in the coordination of Ca(2+) signals between connected hepatocytes.

Glycogenolytic agonists induce coordinated Ca(2+) oscillations in multicellular rat hepatocyte systems as well as in the intact liver. The coordination of intercellular Ca(2+) signals requires functional gap-junction coupling. The mechanisms ensuring this coordination are not precisely known. We investigated possible roles of Ca(2+) or inositol 1,4,5-trisphosphate (InsP(3)) as a coordinating messengers for Ca(2+) spiking among connected hepatocytes. Application of ionomycin or of supra-maximal concentrations of agonists show that Ca(2+) does not significantly diffuse between connected hepatocytes, although gap junctions ensure the passage of small signaling molecules, as demonstrated by FRAP experiments. By contrast, coordination of Ca(2+) spiking among connected hepatocytes can be favored by a rise in the level of InsP(3), via the increase of agonist concentrations, or by a shift in the affinity of InsP(3) receptor for InsP(3). In the same line, coordination cannot be achieved if the InsP(3) is rapidly metabolized by InsP(3)-phosphatase in one cell of the multiplet. These results demonstrate that even if small amounts of Ca(2+) diffuse across gap junctions, they most probably do not play a significant role in inducing a coordinated Ca(2+) signal among connected hepatocytes. By contrast, coordination of Ca(2+) oscillations is fully dependent on the diffusion of InsP(3) between neighboring cells.

Animals↗

Predicting sprint kinematic parameters from anaerobic field tests in physical education students.

The relations among kinematic parameters measured during the first 10 seconds of 100-m sprint and anaerobic tests were studied in 22 male physical education students. During the first 10 seconds of the sprint, the position of the runners was "continuously" measured with a laser telemeter. Maximal acceleration (Amax), maximal velocity (Vmax), and time to reach Vmax (tVmax) were derived from position data. In addition, the subjects performed anaerobic tests: squat jump (SJ), countermovement jump (CMJ), and force-velocity test to measure maximal power, maximal theoretical cranking velocity (VO), maximal theoretical isometric force, and the Wingate anaerobic test (30 seconds). The mean 100-m run time of the subjects was 12.6 +/- 0.9 seconds. The highest correlations were calculated between Amax and V0 (r = 0.55, p < 0.01) and CMJ (r = 0.48, p < 0.05) and Vmax and SJ (r = 0.63, p < 0.01) and CMJ (r = 0.56, p < 0.05). The tVmax was uncorrelated to other tests. Because the CMJ was the anaerobic performance best correlated to the different kinematic parameters of the run, our results fail to identify one anaerobic test that specifically explains one sprint kinematic parameter.

Adult↗

Activation of the liver glycogen phosphorylase by Ca(2+)oscillations: a theoretical study.

Cytosolic calcium plays a crucial role as a second messenger in cellular signalling. Various cell types, including hepatocytes, display Ca(2+)oscillations when stimulated by an extracellular signal. However, the biological relevance of this temporal organization remains unclear. In this paper, we investigate theoretically the effect of Ca(2+)oscillations on a particular example of cell regulation: the phosphorylation-dephosphorylation cycle controlling the activation of glycogen phosphorylase in hepatocytes. By modelling periodic sinusoidal variations in the intracellular Ca(2+)concentration, we show that Ca(2+)oscillations reduce the threshold for the activation of the enzyme. Furthermore, as the activation of a given enzyme depends on the kinetics of its phosphorylation-dephosphorylation cycle, specificity can be encoded by the oscillation frequency. Finally, using a model for signal-induced Ca(2+)oscillations based on Ca(2+)-induced Ca(2+)release, we show that realistic Ca(2+)oscillations can potentiate the response to a hormonal stimulation. These results indicate that Ca(2+)oscillations in hepatocytes could contribute to increase the efficiency and specificity of cellular signalling, as shown experimentally for gene expression in lymphocytes (Dolmetsch et al., 1998).

Animals↗

Hierarchical organization of calcium signals in hepatocytes: from experiments to models.

The proper working of the liver largely depends on the fine tuning of the level of cytosolic Ca(2+) in hepatocytes. Thanks to the development of imaging techniques, our understanding of the spatio-temporal organization of intracellular Ca(2+) in this - and other - cell types has much improved. Many of these signals are mediated by a rise in the level of inositol 1,4,5-trisphosphate (InsP(3)), a second messenger which can activate the release of Ca(2+) from the endoplasmic reticulum. Besides the now well-known hepatic Ca(2+) oscillations induced by hormonal stimulation, intra- and intercellular Ca(2+) waves have also been observed. More recently, subcellular Ca(2+) increases associated with the coordinated opening of a few Ca(2+) channels have been reported. Given the complexity of the regulations involved in the generation of such processes and the variety of time and length scales necessary to describe those phenomena, theoretical models have been largely used to gain a precise and quantitative understanding of the dynamics of intracellular Ca(2+). Here, we review the various aspects of the spatio-temporal organization of cytosolic Ca(2+) in hepatocytes from the dual point of view provided by experiments and modeling. We first focus on the description and the mechanism of intracellular Ca(2+) oscillations and waves. Second, we investigate in which manner these repetitive Ca(2+) increases are coordinated among a set of hepatocytes coupled by gap junctions, a phenomenon known as 'intercellular Ca(2+) waves'. Finally, we focus on the so-called elementary Ca(2+) signals induced by low InsP(3) concentrations, leading to Ca(2+) rises having a spatial extent of a few microns. Although these small-scale events have been mainly studied in other cell types, we theoretically infer general properties of these localized intracellular Ca(2+) rises that could also apply to hepatocytes.

Animals↗

[Marchiafava-Bignani disease of good prognosis. Two cases].

BACKGROUND: Marchiafava-Bignami disease or corpus callosum necrosis, is an uncommon complication of chronic alcoholism. Prognosis is severe. CASE REPORTS: Two young adults with chronic alcoholism who developed Marchiafava-Bignami disease initially improved clinically. DISCUSSION: Diagnosis has been facilitated with MRI. An MRI exploration should be performed in chronic alcoholic patients presenting chronic encephalopathy with dementia, dysarthria, hypertonia, and ataxia, or acute encephalopathy with confusion, dumbness, seizures, and hypertonia. Necrosis of the corpus callosum gives the diagnosis of Marchiafava-Bignami disease.

Adult↗

The frequency encoding of pulsatility.

Examples of pulsatile signalling abound in intercellular communication, suggesting that this phenomenon represents a major function of biological rhythms. Pulsatile signals can be encoded in terms of their frequency and prove more efficient than monotonous ones whenever constant stimulation induces desensitization of target cells. We address the main examples of frequency encoding of pulsatility, besides those of neuronal nature. Considered in turn are cAMP oscillations in the slime mould Dictyostelium discoideum, the pulsatile secretion of hormones such as gonadotropin-releasing hormone or growth hormone, intracellular Ca2+ oscillations, and circadian rhythms. Models based on receptor desensitization show the possibility of optimizing cellular responses to cAMP signals in Dictyostelium or to pulsatile hormonal stimulation. The models indicate how the optimal duration of the pulsatile signal and the optimal interval between successive pulses vary as a function of the rates or receptor desensitization and resensitization and of the maximum ligand level during stimulation. The frequency encoding of intracellular Ca2+ oscillations appears to rely on another molecular mechanism. Models based on protein phosphorylation by a Ca(2+)-calmodulin activated kinase show that the mean level of phosphorylated protein increases with the frequency of calcium spikes--which itself rises with the degree of stimulation--and that distinct levels of different phosphorylated proteins can be reached for a Ca2+ signal of given frequency.

Animals↗

Mechanism of receptor-oriented intercellular calcium wave propagation in hepatocytes.

Intercellular calcium signals are propagated in multicellular hepatocyte systems as well as in the intact liver. The stimulation of connected hepatocytes by glycogenolytic agonists induces reproducible sequences of intracellular calcium concentration increases, resulting in unidirectional intercellular calcium waves. Hepatocytes are characterized by a gradient of vasopressin binding sites from the periportal to perivenous areas of the cell plate in hepatic lobules. Also, coordination of calcium signals between neighboring cells requires the presence of the agonist at each cell surface as well as gap junction permeability. We present a model based on the junctional coupling of several hepatocytes differing in sensitivity to the agonist and thus in the intrinsic period of calcium oscillations. In this model, each hepatocyte displays repetitive calcium spikes with a slight phase shift with respect to neighboring cells, giving rise to a phase wave. The orientation of the apparent calcium wave is imposed by the direction of the gradient of hormonal sensitivity. Calcium spikes are coordinated by the diffusion across junctions of small amounts of inositol 1,4, 5-trisphosphate (InsP(3)). Theoretical predictions from this model are confirmed experimentally. Thus, major physiological insights may be gained from this model for coordination and spatial orientation of intercellular signals.-Dupont, G., Tordjmann, T., Clair, C., Swillens, S., Claret, M., Combettes, L. Mechanism of receptor-oriented intercellular calcium wave propagation in hepatocytes.

Animals↗

From calcium blips to calcium puffs: theoretical analysis of the requirements for interchannel communication.

In the cytoplasm of cells of different types, discrete clusters of inositol 1,4,5-trisphosphate-sensitive Ca(2+) channels generate Ca(2+) signals of graded size, ranging from blips, which involve the opening of only one channel, to moderately larger puffs, which result from the concerted opening of a few channels in the same cluster. These channel clusters are of unknown size or geometrical characteristics. The aim of this study was to estimate the number of channels and the interchannel distance within such a cluster. Because these characteristics are not attainable experimentally, we performed computer stochastic simulations of Ca(2+) release events. We conclude that, to ensure efficient interchannel communication, as experimentally observed, a typical cluster should contain two or three tens of inositol 1,4,5-trisphosphate-sensitive Ca(2+) channels in close contact.

Animals↗