148 resultados para 6-Phosphofructo-1-kinase
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This research aims toward a better understanding of the organizational culture(s) of the judiciary in Switzerland by analysing what 'good justice' means nowadays in this country. It seeks to clarify whether, and to what extent, expectations of 'good justice' of judicial actors (judges without managerial experience) and of managerial actors (court managers) are similar and to describe possible managerial implications that may result from this. As judges are at the heart of the judicial organization and exert a strong influence on other groups of actors (Sullivan, Warren et al. 1994), the congruence of their expectations with those of court managers will be at the centre of the analysis. Additionally, referring to the conceptual worlds of Boltanski and Thévenaut (1991), we analyze how closely these expectations are to management-oriented values. We found that almost half of expectations are common to the two groups examined and the main quoted ones are compatible to new public management (NPM) concepts. On the other hand, those expectations shared exclusively by judges relate to the human side of justice, whereas those specific to court managers focus on the way justice functions.
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To determine whether a 4-a-side handball (HB) game is an appropriate aerobic stimulus to reach and potentially enhance maximal oxygen uptake (V O(2)max), and whether heart rate (HR) is a valid index of V O(2) during a handball game. Nine skilled players (21.0+/-2.9 yr) underwent a graded maximal aerobic test (GT) where V O(2)max and HR-V O(2) relationship were determined. V O(2), HR and blood lactate ([La](b)) were recorded during a 2 x 225 s (interspersed with 30s rest) 4-a-side handball game and were compared to those measured during an 480-s running intermittent exercise (IE). Mean V O(2) tended to be higher in handball compared to IE (93.9+/-8.5 vs. 87.6+/-7.4% O(2)max, p=0.06), whereas HR was similar (92.3+/-4.9 vs. 93.9+/-3.9% of the peak of HR, p=0.10). [La](b) was lower for handball than for IE (8.9+/-3.5 vs. 11.6+/-2.1 mmol l(-1), p=0.04). Time spent over 90% of V O(2)max was higher for handball than for IE (336.1+/-139.6s vs. 216.1+/-124.7s; p=0.03). The HR-V O(2) relationship during GT was high (r(2)=0.96, p<0.001) but estimated V O(2) from HR was lower to that measured (p=0.03) in handball, whereas there was no difference in IE. 4-a-side handball game can be used as a specific alternative to IE for enhancing aerobic fitness in handball players. Nevertheless, the accuracy of HR measures for estimating V O(2) during handball is poor.
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The aim of the present study was to measure the changes in resting energy expenditure (REE) induced by malaria and to assess to what extent they are related to fever and nutritional status. The REE of 19 Gambian children (mean age +/- SEM, 9 +/- 1 y; weight, 24 +/- 2 kg; expected weight for height 86 +/- 1%) were measured with a hood system at repeated intervals at the onset of malaria crisis (test A), 3 to 4 d after therapy (test B), and 14 to 21 d later (test C). Axillary temperature averaged 39.2 +/- 0.1, 36.6 +/- 0.1, and 36.7 +/- 0.1 degrees C in the tests A, B, and C, respectively. REE in test A was significantly higher than REE in test B (223 +/- 10 versus 174 +/- 8 kJ/kg.d, p less than 0.0001), but in test C (169 +/- 8 kJ/kg.d), it did not differ from that observed in test B. The percentage of increase in REE was significantly correlated with the difference in axillary temperature (r = 0.46, p less than 0.05); the slope of the regression line indicated an increase of 6.9% in REE/degree C of fever. Furthermore, the individual increase in REE/degree C was correlated to the percentage of weight for height of the children (r = 0.54, p less than 0.05), indicating that the child's nutritional status influences the magnitude of the hypermetabolism due to fever. We concluded that Gambian children suffering from an acute episode of malaria have an increase in REE averaging 30%; however, REE promptly returns to baseline value a few days after the beginning of therapy.
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PURPOSE: Hypoxia is known to reduce maximal oxygen uptake (VO(2max)) more in trained than in untrained subjects in several lowland sports. Ski mountaineering is practiced mainly at altitude, so elite ski mountaineers spend significantly longer training duration at altitude than their lower-level counterparts. Since acclimatization in hypobaric hypoxia is effective, the authors hypothesized that elite ski mountaineers would exhibit a VO2max decrement in hypoxia similar to that of recreational ski mountaineers. METHODS: Eleven elite (E, Swiss national team) and 12 recreational (R) ski mountaineers completed an incremental treadmill test to exhaustion in normobaric hypoxia (H, 3000 m, F(1)O(2) 14.6% ± 0.1%) and in normoxia (N, 485 m, F(1)O(2) 20.9% ± 0.0%). Pulse oxygen saturation in blood (SpO(2)), VO(2max), minute ventilation, and heart rate were recorded. RESULTS: At rest, hypoxic ventilatory response was higher (P < .05) in E than in R (1.4 ± 1.9 vs 0.3 ± 0.6 L · min⁻¹ · kg⁻¹). At maximal intensity, SpO(2) was significantly lower (P < .01) in E than in R, both in N (91.1% ± 3.3% vs 94.3% ± 2.3%) and in H (76.4% ± 5.4% vs 82.3% ± 3.5%). In both groups, SpO(2) was lower (P < .01) in H. Between N and H, VO(2max) decreased to a greater extent (P < .05) in E than in R (-18% and -12%, P < .01). In E only, the VO(2max) decrement was significantly correlated with the SpO(2) decrement (r = .74, P < .01) but also with VO(2max) measured in N (r = .64, P < .05). CONCLUSION: Despite a probable better acclimatization to altitude, VO(2max) was more reduced in E than in R ski mountaineers, confirming previous results observed in lowlander E athletes.
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Chronic growth hormone (GH) hypersecretion in rats leads to increased isometric force without affecting the unloaded shortening velocity of isolated cardiac papillary muscles, despite a marked isomyosin shift toward V3. To determine if alterations occurred at the level of the contractile proteins in rats bearing a GH-secreting tumor (GH rats), we examined the mechanical properties of skinned fibers to eliminate the early steps of the excitation-contraction coupling mechanism. We found that maximal active tension and stiffness at saturating calcium concentrations (pCa 4.5) were markedly higher in GH rats than in control rats (tension, 52.9 +/- 5.2 versus 38.1 +/- 4.6 mN.mm-2, p < 0.05; stiffness, 1,105 +/- 120 versus 685 +/- 88 mN.mm-2.microns-1, p < 0.01), whereas values at low calcium concentrations (pCa 9) were unchanged. In addition, the calcium sensitivity of the contractile proteins was slightly but significantly higher in GH rats than in control rats (delta pCa 0.04, p < 0.001). The crossbridge cycling rate, reflected by the response to quick length changes, was lower in GH rats than in control rats (62.0 +/- 2.6 versus 77.4 +/- 6.6 sec-1, p < 0.05), in good agreement with a decrease in the proportion of alpha-myosin heavy chains in the corresponding papillary muscles (45.5 +/- 2.0% versus 94.6 +/- 2.4%, p < 0.001). The changes in myosin heavy chain protein phenotype were paralleled by similar changes of the corresponding mRNAs, indicating that the latter occurred mainly at a pretranslational level. These results demonstrate that during chronic GH hypersecretion in rats, alterations at the myofibrillar level contribute to the increase in myocardial contractility observed in intact muscle.
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Eusocial societies are traditionally characterized by a reproductive division of labor, an overlap of generations, and cooperative care of the breeders' young. Eusociality was once thought to occur only in termites, ants, and some bee and wasp species, but striking evolutionary convergences have recently become apparent between the societies of these insects and those of cooperatively breeding birds and mammals. These parallels have blurred distinctions between cooperative breeding and eusociality, leading to calls for either drastically restricting or expanding wage of these terms. We favor the latter approach. Cooperative breeding and eusociality are not discrete phenomena, but rather form a continuum of fundamentally similar social systems whose main differences lie in the distribution of lifetime reproductive success among group members. Therefore we propose to array vertebrate and invertebrate cooperative breeders along a common axis, representing a standardized measure of reproductive variance, and to drop such (loaded) terms as ''primitive'' and ''advanced'' eusociality. The terminology we propose unites all occurrences of alloparental helping of kin under a single theoretical umbrella (e.g., Hamilton's rule). Thus, cooperatively breeding vertebrates can be regarded as eusocial, just as eusocial inverbrates are cooperative breeders. We believe this integrated approach will foster potentially revealing cross-taxon comparisons, which are essential to understanding social evolution in birds, mammals, and in sects.
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Si La notion de Bien commun paraît de prime abord trop ambitieuse, trompeuse en ses promesses excessives et inaccessibles, elle est néanmoins nécessaire au débat éthique dans l'espace public contemporain. Dans cette contribution, nous voudrions montrer comment une compréhension critique de la notion controversée de Bien commun peut s'avérer compatible avec une prise en compte réaliste et responsable des conflits d'intérêts et de la délibération éthique. L'exemple du débat français sur la laïcité permet à cet égard de comprendre la nécessité de dépasser l'opposition stérile entre un communautarisme poussé à l'extrême et un universalisme vidé de sa pertinence historique et dialectique. If, at the first look, the notion of the common Good seems too ambitious, making excessive and unaccessible promises, it is nevertheless necessary to use it in the ethical public discussion. This paper aims to show that a critical understanding of this controversial idea of the common Good may help to solve some conflicts of interests. The example of the french debate on laicity should help us to overcome the fallacious opposition between extreme communitarianism and abstract universalism.
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A sensitive and specific ultra performance liquid chromatography-tandem mass spectrometry method for the simultaneous quantification of nicotine, its metabolites cotinine and trans-3'-hydroxycotinine and varenicline in human plasma was developed and validated. Sample preparation was realized by solid phase extraction of the target compounds and of the internal standards (nicotine-d4, cotinine-d3, trans-3'-hydroxycotinine-d3 and CP-533,633, a structural analog of varenicline) from 0.5mL of plasma, using a mixed-mode cation exchange support. Chromatographic separations were performed on a hydrophilic interaction liquid chromatography column (HILIC BEH 2.1×100mm, 1.7μm). A gradient program was used, with a 10mM ammonium formate buffer pH 3/acetonitrile mobile phase at a flow of 0.4mL/min. The compounds were detected on a triple quadrupole mass spectrometer, operated with an electrospray interface in positive ionization mode and quantification was performed using multiple reaction monitoring. Matrix effects were quantitatively evaluated with success, with coefficients of variation inferior to 8%. The procedure was fully validated according to Food and Drug Administration guidelines and to Société Française des Sciences et Techniques Pharmaceutiques. The concentration range was 2-500ng/mL for nicotine, 1-1000ng/mL for cotinine, 2-1000ng/mL for trans-3'-hydroxycotinine and 1-500ng/mL for varenicline, according to levels usually measured in plasma. Trueness (86.2-113.6%), repeatability (1.9-12.3%) and intermediate precision (4.4-15.9%) were found to be satisfactory, as well as stability in plasma. The procedure was successfully used to quantify nicotine, its metabolites and varenicline in more than 400 plasma samples from participants in a clinical study on smoking cessation.
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BACKGROUND: The purpose of this work was to characterize the expression of drug and nutrient carriers along the anterior-posterior and crypt-villus axes of the intestinal epithelium and to study the validity of utilizing whole gut tissue rather than purified epithelial cells to examine regional variations in gene expression. RESULTS: We have characterized the mRNA expression profiles of 76 % of all currently known transporters along the anterior-posterior axis of the gut. This is the first study to describe the expression profiles of the majority of all known transporters in the intestine. The expression profiles of transporters, as defined according to the Gene Ontology consortium, were measured in whole tissue of the murine duodenum, jejunum, ileum and colon using high-density microarrays. For nine transporters (Abca1, Abcc1, Abcc3, Abcg8, Slc10a2, Slc28a2, Slc2a1, Slc34a2 and Slc5a8), the mRNA profiles were further measured by RT-PCR in laser micro-dissected crypt and villus epithelial cells corresponding to the aforementioned intestinal regions. With respect to differentially regulated transporters, the colon had a distinct expression profile from small intestinal segments. The majority (59 % for p cutoff < or = 0.05) of transporter mRNA levels were constant across the intestinal sections studied. For the transporter subclass "carrier activity", which contains the majority of known carriers for biologically active compounds, a significant change (p < or = 0.05) along the anterior-posterior axis was observed. CONCLUSION: All nine transporters examined in laser-dissected material demonstrated good replication of the region-specific profiles revealed by microarray. Furthermore, we suggest that the distribution characteristics of Slc5a8 along the intestinal tract render it a suitable candidate carrier for monocarboxylate drugs in the posterior portion of the intestine. Our findings also predict that there is a significant difference in the absorption of carrier-mediated compounds in the different intestinal segments. The most pronounced differences can be expected between the adjoining segments ileum and colon, but the differences between the other adjoining segments are not negligible. Finally, for the examined genes, profiles measured in whole intestinal tissue extracts are representative of epithelial cell-only gene expression.
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BACKGROUND: Isolated congenital atrioventricular block (CAVB) diagnosed in utero is associated with a high morbidity and mortality. Prognosis is especially poor when heart rate drops below 55 beats per minute (bpm) and when fetal hydrops develops. We describe the natural history and outcome of 24 infants with isolated CAVB diagnosed in utero, review the literature, and assess the risk factors that could predict outcome. METHODS: This was a retrospective multicenter study of 24 patients with isolated CAVB diagnosed in utero. RESULTS: CAVB was detected at a mean gestational age (GA) of 24.7 +/- 5.1 weeks. Ten fetuses initially presented with complete heart block. Low heart rate or incomplete heart block was the first documentation of bradyarrhythmia in the other 14 fetuses. In 11 of them, CAVB developed during pregnancy after a median time of 3 (range 1-16) weeks. Fetal hydrops developed in 10 of 24 (42%) fetuses at a mean GA of 27.6 +/- 5.1 weeks. Hydropic fetuses showed lower heart rates during pregnancy (47 +/- 10 bpm) than non-hydropic fetuses (57 +/- 10 bpm). There were three intrauterine deaths; all were hydropic and female. Nine viable females and 12 males were born at a mean GA of 37.1 +/- 6.1 weeks with an average birth weight of 3097 +/- 852 g. Fifteen CAVB patients required pacemaker (PM) intervention, 10 of them immediately after birth. Dilated cardiomyopathy (DCM) developed in three infants of whom two died of congestive heart failure, shortly after the diagnosis was made; one is still alive. Mortality before or after birth was 21%, and was associated with heart rates below 50 bpm and development of fetal hydrops. Poor outcome, defined as death, PM implantation, or development of DCM, occurred in 83% of cases and was associated with heart rates below 60 bpm during pregnancy. CONCLUSIONS: Isolated CAVB diagnosed in utero is associated with high morbidity and mortality. Patients who develop fetal hydrops show lower heart rates during pregnancy than patients who do not. A fetal heart rate below 50 bpm and development of fetal hydrops is associated with increased mortality. Rates below 60 bpm are associated with PM requirement and/or DCM.
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Contexte: L'ensemble des phénomènes aigus suivant un arrêt cardio-respiratoire (ACR) est décrit sous le nom de maladie de post-réanimation (MPR) (post-resuscitation disease). Celle- ci est la conséquence du syndrome de reperfusion et est caractérisée par une réponse inflammatoire systémique intense, d'allure septique. La procalcitonine (PCT) est un marqueur aigu de la réponse inflammatoire systémique, qui a été beaucoup étudiée aux soins intensifs (SI) dans le contexte du sepsis, et constitue un outil diagnostic et pronostique important. Toutefois la PCT n'est pas un marqueur spécifique pour le sepsis mais peut également augmenter lors de réponse inflammatoire systémique d'origine non infectieuse. Objectifs: 1) Evaluer s'il existe une corrélation entre la valeur plasmatique de PCT et la MPR ; 2) examiner la relation entre le taux au pic de PCT et le pronostic des patients avec coma post-ACR ; 3) comparer la valeur pronostique de la PCT à celle d'un marqueur pronostic connu du coma post-anoxique tel que la neuron specific enolase (NSE). Méthodologie: Analyse d'une base de données prospective comprenant des patients admis aux SI du centre hospitalier universitaire vaudoise (CHUV) entre décembre 2009 et juillet 2011 en raison d'un ACR et traités par hypothermie thérapeutique (33 - 34 °C pendant 24h), selon notre protocole standard de prise en charge. La concentration plasmatique de PCT est mesurée à 24-72h après ACR, la valeur maximale (PCTmax) étant incluse dans l'analyse. La durée de l'arrêt circulatoire et le score de SOFA (Sequential Organ Failure Assessment) sont utilisés pour quantifier la sévérité de la MPR. Le pronostic est composé de la mortalité hospitalière, ainsi que la mortalité et la récupération neurologique à trois mois, mesurée avec le score de « Cerebral Performance Categories » (CPC), dichotomisé en bonne récupération (CPC 1 = pas de handicap ; CPC 2 = handicap modéré) et mauvaise récupération (CPC 3 = handicap sévère ; CPC 4 = état végétatif ; CPC 5 = décès). Résultats: 68 patients consécutifs (âge médian 65 ans, durée médiane totale de l'arrêt circulatoire [time to ROSC] 20.5 min) ont été étudiés. La PCTmax corrélait avec la durée de l'arrêt circulatoire (p = 0.001) ainsi qu'avec les scores de SOFA à l'admission et aux jours 1 et 2 (p<0.001 pour les trois associations). Une association significative a été observée entre la PCTmax et la survie hospitalière (médiane 3.9 [écart interquartile (EI) 1.0 - 16.8] chez les non-survivants vs. 1.4 [EI 0.6 - 6.2] ng/ml chez les survivants, p=0.032) et à trois mois (médiane 3.8 ([EI 1.0 - 15.6] vs. 1.4 [EI 0.5 - 6.0] ng/ml, p=0.034). La PCTmax était aussi plus basse chez les patients avec bonne récupération neurologique à trois mois (p=0.064). En comparaison avec la NSEmax, la PCTmax avait une valeur prédictive supérieure pour la sévérité de la maladie de post-réanimation et inférieure pour le pronostic. Conclusions: La valeur plasmatique maximale de PCT corrèle avec la sévérité de la MPR et est associé à la mortalité et à l'état neurologique à trois mois après coma post-anoxique. Ces données suggèrent que la PCT peut être un marqueur utile dans la prise en charge des patients comateux après ACR et hypothermie thérapeutique. Des études à plus large échelle sont en cours pour confirmer ces résultats.
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Astrocytes have recently become a major center of interest in neurochemistry with the discoveries on their major role in brain energy metabolism. An interesting way to probe this glial contribution is given by in vivo (13) C NMR spectroscopy coupled with the infusion labeled glial-specific substrate, such as acetate. In this study, we infused alpha-chloralose anesthetized rats with [2-(13) C]acetate and followed the dynamics of the fractional enrichment (FE) in the positions C4 and C3 of glutamate and glutamine with high sensitivity, using (1) H-[(13) C] magnetic resonance spectroscopy (MRS) at 14.1T. Applying a two-compartment mathematical model to the measured time courses yielded a glial tricarboxylic acid (TCA) cycle rate (Vg ) of 0.27 ± 0.02 μmol/g/min and a glutamatergic neurotransmission rate (VNT ) of 0.15 ± 0.01 μmol/g/min. Glial oxidative ATP metabolism thus accounts for 38% of total oxidative metabolism measured by NMR. Pyruvate carboxylase (VPC ) was 0.09 ± 0.01 μmol/g/min, corresponding to 37% of the glial glutamine synthesis rate. The glial and neuronal transmitochondrial fluxes (Vx (g) and Vx (n) ) were of the same order of magnitude as the respective TCA cycle fluxes. In addition, we estimated a glial glutamate pool size of 0.6 ± 0.1 μmol/g. The effect of spectral data quality on the fluxes estimates was analyzed by Monte Carlo simulations. In this (13) C-acetate labeling study, we propose a refined two-compartment analysis of brain energy metabolism based on (13) C turnover curves of acetate, glutamate and glutamine measured with state of the art in vivo dynamic MRS at high magnetic field in rats, enabling a deeper understanding of the specific role of glial cells in brain oxidative metabolism. In addition, the robustness of the metabolic fluxes determination relative to MRS data quality was carefully studied.