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X Leverve

Publications and source records attributed to X Leverve.

At least 37 records · Page 2Linked to original sources
PubMed1999

Nutritional status of haemodialysis patients: a French national cooperative study. French Study Group for Nutrition in Dialysis.

BACKGROUND: Despite the severity and the prognosis value of undernutrition in haemodialysed patients, no large study is available as yet in Europe. Hence, this French National Cooperative Study aimed to determine the prevalence of undernutrition and its relationship to dialysis efficacy. METHODS: Nutritional status was determined in 7123 patients (i.e. one-third of the French haemodialysis population) using body mass index (BMI), predialysis haemoglobin, albumin, pre-albumin, cholesterol, and also normalized protein catabolic rate (nPCR) and lean body mass (LBM) calculated from pre- and postdialysis urea and creatinine. Dialysis treatment was estimated from weekly dialysis time and KtV determination. RESULTS: Dialysis time was 12.4+/-2.7 h/week and KtV 1.36+/-0.36. BMI was below 20 kg/m2 in 24% and the observed/expected LBM ratio below 90% in 62%. Albumin, pre-albumin and nPCR were below the high-risk thresholds of 35 g/l, 300 mg/l and 1g/kg/day in 20%, 36% and 35% of patients, respectively. Pre-albumin was the most representative nutritional parameter. Albumin, pre-albumin and LBM correlated with nPCR. A dialysis time above 12 h/week was associated with higher BMI, albumin, pre-albumin and LBM. LBM was higher in patients with a KtV value >1.1. CONCLUSION: This study showed life-threatening undernutrition in 20-36% of the studied population, according to nutritional parameters. Protein intake (estimated by nPCR) and dialysis efficacy (estimated by dialysis time and KtV) appeared to be major determinants of nutritional status in this population.

Adult↗
PubMed1999

Effect of major hepatectomy on glucose and lactate metabolism.

BACKGROUND: The liver plays an important role in glucose and lactate metabolism. Major hepatectomy may therefore be suspected to cause alterations of glucose and lactate homeostasis. METHODS: Thirteen subjects were studied: six patients after major hepatectomy and seven healthy subjects who had fasted overnight. Glucose turnover was measured with 6,6(2)H glucose. Lactate metabolism was assessed using two complementary approaches: 13C-glucose synthesis and 13CO2 production from an exogenous 13C-labeled lactate load infused over 15 minutes were measured, then the plasma lactate concentrations observed over 185 minutes after lactate load were fitted using a biexponential model to calculate lactate clearance, endogenous production, and half-lives. RESULTS: Three to five liver segments were excised. Compared to healthy controls, the following results were observed in the patients: 1) normal endogenous glucose production; 2) unchanged 13C-lactate oxidation and transformation into glucose; 3) similar basal plasma lactate concentration, lactate clearance, and lactate endogenous production; 4) decreased plasma lactate half-life 1 and increased half-life 2. CONCLUSIONS: Glucose and lactate metabolism are well maintained in patients after major hepatectomy, demonstrating a large liver functional reserve. Reduction in the size of normal liver parenchyma does not lead to hyperlactatemia. The use of a pharmacokinetic model, however, allows the detection of subtle alterations of lactate metabolism.

Adult↗
PubMed1999

[Cellular energy metabolism: physiologic and pathologic aspects].

Cellular homeostasis requires permanent energy production and consumption. Adenosine triphosphate (ATP) is the major energy component for the cell. Its synthesis occurs mainly in mitochondria where the oxidative phosphorylations realise the coupling between oxygen consumption and phosphorylation of adenosine diphosphate. The anaerobic production of ATP plays an important role in the intermediary metabolism. The enzymatic complexes of the mitochondrial respiratory chain are energy transducers acting as proton pumps. In cardiomyocytes, the phosphocreatine circuit allows a substrate channelling between mitochondria and myofibrils. This metabolic compartmentation explains the difficulties of studying energetic metabolism in the beating heart and the lack of correlation between cardiac function and the usual energy parameters. Mitochondria are a potential site of action of anaesthetic agents. Lipophilic local anaesthetics impair cellular energy metabolism and mitochondrial ATP production. Such effects could be associated with toxic effects of these molecules. NMR or near-infrared spectroscopy are non invasive techniques for monitoring energetic metabolism in vivo. Clinical applications are developed for analysing brain, muscle or cardiac function in physiological and pathological conditions.

Adenosine Triphosphate↗
PubMed1998

Flux-force relationships in intact cells: a helpful tool for understanding the mechanism of oxidative phosphorylation alterations?

On isolated mitochondria, numerous studies of the relationships between fluxes and their associated forces have led to the description of some properties of the oxidative phosphorylation pathway. However whether such an approach can be applied to understanding the actual situation in intact living cells needs further consideration. In this study on isolated hepatocytes, we describe the dependence of the respiratory rate on the three thermodynamic forces linked to oxidative phosphorylation (i.e. the redox span over the respiratory chain, the electrical potential difference across the inner mitochondrial membrane and the free energy of ATP synthesis reaction). Even if this description is phenomenological and some objections may be raised regarding the relevance of such a bulk-phase force estimation, we present some results showing that the study of flux-force relationships in intact cells may be a helpful approach for understanding the mechanisms by which oxidative phosphorylation activity is changed.

Adenosine Triphosphate↗
PubMed1998

2,4 Dinitrophenol-uncoupling effect on delta psi in living hepatocytes depends on reducing-equivalent supply.

Mitochondrial uncouplers, such as 2,4 dinitrophenol (DNP), increase the cellular respiration by decreasing mitochondrial membrane potential (delta psi). We show that this respiratory effect can be transient or even prevented in isolated liver cells depending on the exogenous substrate used (dihydroxyacetone vs. octanoate or proline). Moreover the decrease in ATP/ADP ratio induced by DNP is partially restored by addition of octanoate or proline. By using rhodamine 123 (Rh123) monitored by flow cytometry in living hepatocytes, we were able to follow in time delta psi in such DNP-uncoupled cells incubated with various substrates. The ability of this method to evaluate delta psi changes was assessed by using myxothiazol (3.6 microM), an inhibitor of the b-c1 complex of the respiratory chain which decreased delta psi (65%), or oligomycin (6 microg/ml), an inhibitor of the F0F1-ATPase which increased it (50%). Although DNP induced a dose-dependent decrease of delta psi, we found that octanoate or proline addition prevented such effect. We propose that octanoate or proline may counteract the uncoupling effect of DNP by providing a high supply of reducing equivalents to the respiratory chain.

2,4-Dinitrophenol↗
PubMed1998

Enteral nutrition in intensive care patients: a practical approach. Working Group on Nutrition and Metabolism, ESICM. European Society of Intensive Care Medicine.

Severe protein-calorie malnutrition is a major problem in many intensive care (ICU) patients, due to the increased catabolic state often associated with acute severe illness and the frequent presence of prior chronic wasting conditions. Nutritional support is thus an important part of the management of these patients. Over the years, enteral nutrition (EN) has gained considerable popularity, due to its favorable effects on the digestive tract and its lower cost and rate of complications compared to parenteral nutrition. However, clinicians caring for ICU patients are often faced with contradictory data and difficult decisions when having to determine the optimal timing and modalities of EN administration, estimation of patient requirements, and choice of formulas. The purpose of this paper is to provide practical guidelines on these various aspects of enteral nutritional support, based on presently available evidence.

Cost-Benefit Analysis↗
PubMed1998

Hypocapnia does not alter hepatic blood flow or oxygen consumption in patients with head injury.

OBJECTIVE: To evaluate the effects of hypocapnia on the systemic and hepatic circulations and oxygenation values in patients with head injury. DESIGN: Open-label, prospective study. SETTING: University hospital, department of anesthesiology and intensive care unit. PATIENTS: Eleven mechanically ventilated patients with isolated head trauma and stable hemodynamic status. INTERVENTIONS: At the beginning of the study, each patient presented with normocapnic ventilation. Mechanical hyperventilation was then adjusted to obtain stable hypocapnia over an interval of 24 hrs. Cardiac output and other systemic hemodynamic parameters were measured, using a pulmonary artery catheter. Hepatic parameters were measured via a catheter inserted into the hepatic vein. Total hepatic blood flow was determined by the Fick principle using a continuous infusion of indocyanine green. Arterial and hepatic venous blood gases were sampled to determine systemic and hepatic-splanchnic oxygenation. Measurements were done at the end of the four phases: a) 30 mins of normocapnia (N); b) 30 mins of hypocapnia (H0); c) 3 hrs of hypocapnia (H3); and d) 24 hrs of hypocapnia (H24). Intracranial pressure and cerebral perfusion pressure were hourly monitored throughout the study. MEASUREMENTS AND MAIN RESULTS: There were no significant changes in systemic hemodynamic parameters. The hepatic blood flow index did not differ from normocapnia (N 1.8 +/- 0.4 L/min/m2) to hypocapnia (H0 1.6 +/- 0.3 L/min/m2; H3 1.7 +/- 0.4 L/min/m2; H24 1.7 +/- 0.4 L/min/m2). The ratio of hepatic blood flow index to cardiac index remained stable throughout the study. Hypocapnia did not affect hepatic-splanchnic oxygen delivery and consumption. CONCLUSIONS: Hypocapnic hyperventilation does not alter hepatic hemodynamic parameters in patients with head injury. This result may be related to the lack of changes in cardiac output or in the hepatic vasoreactivity. Moreover, hypocapnia does not modify hepatic-splanchnic oxygenation. Thus, in case of intracranial hypertension, hypocapnia might be used without undesirable effect on the hepatic-splanchnic perfusion.

Adult↗
PubMed1998

A generic model for Internet-accessed databases in epidemiology: a nutritional application.

The Web technology has made the exchange of information among heterogeneous platforms possible with no added cost to end-users. Adding to this, it made it possible to access databases residing on servers in different geographic locations giving thus conceptors and programmers the possibility of making distributed applications with a fraction of the time needed before. This technology is therefore very well suited to medical applications which are normally multi-user, multiplatform, and data-intensive. In this paper, we present an application for epidemiological studies based on the Web technology and the reuse of common concepts in epidemiology to produce a generic model that can be parameterisable by the end-user to suit the needs of his study. This model is then applied to develop an application to optimise the collection and processing of nutritional data for a nation-wide epidemiological study concerning renal failure patients.

Databases, Factual↗
PubMed1998

Quantitative analysis of some mechanisms affecting the yield of oxidative phosphorylation: dependence upon both fluxes and forces.

The purpose of this work was to show how the quantitative definition of the different parameters involved in mitochondrial oxidative phosphorylation makes it possible to characterize the mechanisms by which the yield of ATP synthesis is affected. Three different factors have to be considered: (i) the size of the different forces involved (free energy of redox reactions and ATP synthesis, proton electrochemical difference); (ii) the physical properties of the inner mitochondrial membrane in terms of leaks (H+ and cations); and finally (iii) the properties of the different proton pumps involved in this system (kinetic properties, regulation, modification of intrinsic stoichiometry). The data presented different situations where one or more of these parameters are affected, leading to a different yield of oxidative phosphorylation. (1) By manipulating the actual flux through each of the respiratory chain units at constant protonmotive force in yeast mitochondria, we show that the ATP/O ratio decreases when the flux increases. Moreover, the highest efficiency was obtained when the respiratory rate was low and almost entirely controlled by the electron supply. (2) By using almitrine in different kinds of mitochondria, we show that this drug leads to a decrease in ATP synthesis efficiency by increasing the H+/ATP stoichiometry ofATP synthase (Rigoulet M et al. Biochim Biophys Acta 1018: 91-97, 1990). Since this enzyme is reversible, it was possible to test the effect of this drug on the reverse reaction of the enzyme i.e. extrusion of protons catalyzed by ATP hydrolysis. Hence, we are able to prove that, in this case, the decrease in efficiency of oxidative phosphorylation is due to a change in the mechanistic stoichiometry of this proton pump. To our knowledge, this is the first example of a modification in oxidative phosphorylation yield by a change in mechanistic stoichiometry of one of the proton pumps involved. (3) In a model of polyunsaturated fatty acid deficiency in rat, it was found that non-ohmic proton leak was increased, while ohmic leak was unchanged. Moreover, an increase in redox slipping was also involved, leading to a complex picture. However, the respective role of these two mechanisms may be deduced from their intrinsic properties. For each steady state condition, the quantitative effect of these two mechanisms in the decrease of oxidative phosphorylation efficiency depends on the values of different fluxes or forces involved. (4) Finally the comparison of the thermokinetic data in view of the three dimensional-structure of some pumps (X-ray diffraction) also gives some information concerning the putative mechanism of coupling (i.e. redox loop or proton pump) and their kinetic control versus regulation of mitochondrial oxidative phosphorylation.

ATP Synthetase Complexes↗
PubMed1998

Oxidative phosphorylation in intact hepatocytes: quantitative characterization of the mechanisms of change in efficiency and cellular consequences.

Two mechanisms may affect the yield of the oxidative phosphorylation pathway in isolated mitochondria: (i) a decrease in the intrinsic coupling of the proton pumps (H+/2e- or H+/ATP), and (ii) an increase in the inner membrane conductance (proton or cation leak). Hence three kinds of modifications can occur and each of them have been characterized in isolated rat liver mitochondria (see preceding chapter by Rigoulet et al.). In intact isolated hepatocytes, these modifications are linked to specific patterns of bioenergetic parameters, i.e. respiratory flux, mitochondrial redox potential, DY, and phosphate potential. (1) The increase in H+/ATP stoichiometry of the mitochondrial ATP synthase, as induced by almitrine [20], leads to a decrease in mitochondrial and cytosolic ATP/ADP ratios without any change in the protonmotive force nor in the respiratory rate or redox potential. (2) In comparison to carbohydrate, octanoate metabolism by beta-oxidation increases the proportion of electrons supplied at the second coupling site of the respiratory chain. This mimics a redox slipping. Octanoate addition results in an increased respiratory rate and mitochondrial NADH/NAD ratio while protonmotive force and phosphate potential are almost unaffected. The respiratory rate increase is associated with a decrease in the overall apparent thermodynamic driving force (2deltaE'o - ndeltap) which confirms the 'redox-slipping-like' effect. (3) An increase in proton conductance as induced by the protonophoric uncoupler 2,4-dinitrophenol (DNP) leads to a decrease, as expected, in the mitochondrial NADH/NAD and ATP/ ADP ratios and in deltapsi while respiratory rate is increased. Thus, each kind of modification (proton leak, respiratory chain redox slipping or increase in H+/ATP stoichiometry of ATPase) is related to a specific set of bioenergetic parameters in intact cells. Moreover, these patterns are in good agreement with the data found in isolated mitochondria. From this work, we conclude that quantitative analysis of four bioenergetic parameters (respiration rate, mitochondrial NADH/ NAD ratio, protonmotive force and mitochondrial phosphate potential) gives adequate tools to investigate the mechanism by which some alterations may affect the yield of the oxidative phosphorylation pathway in intact cells.

2,4-Dinitrophenol↗
PubMed1998

[A 1993-1995 epidemiological survey of home parenteral nutrition in approved centers for adults in France].

OBJECTIVES: A 1993-1995 three year epidemiological survey of home parenteral nutrition was performed through in France in approved centers for adults. METHODS: Data were retrospectively collected each year on a standardized questionnaire focussing on indications and short term outcome. RESULTS: All centers (n = 14) participated in the study and 524 new adult patients were recruited. The overall incidence was unchanged at 3.75 patients/10(6) adults. Indications for AIDS rose (8 to 18%) whereas other indications were stable. Prevalence increased by 19%: 4.40 adults/10(6) patients at 01.01.1996. At six months, the probability to stay on treatment was 19.5% for AIDS and cancer indications but 52% for others, whereas death rates were 59% and 9% respectively. CONCLUSIONS: For both cancer and AIDS indications, short-term treatment was due to a poor prognosis. For other diagnosis, complicated with a short bowel in 51% of cases, prognosis was excellent but associated with treatment dependency. The latter point focuses on the need for additional treatments in irreversible intestinal failure.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Study of regulation of mitochondrial respiration in vivo. An analysis of influence of ADP diffusion and possible role of cytoskeleton.

The purpose of this work was to investigate the mechanism of regulation of mitochondrial respiration in vivo in different muscles of normal rat and mice, and in transgenic mice deficient in desmin. Skinned fiber technique was used to study the mitochondrial respiration in the cells in vivo in the heart, soleus and white gastrocnemius skeletal muscles of these animals. Also, cardiomyocytes were isolated from the normal rat heart, permeabilized by saponin and the "ghost" (phantom) cardiomyocytes were produced by extraction of myosin with 800 mM KCl. Use of confocal immunofluorescent microscopy and anti-desmin antibodies showed good preservation of mitochondria and cytoskeletal system in these phantom cells. Kinetics of respiration regulation by ADP was also studied in these cells in detail before and after binding of anti-desmine antibodies with intermediate filaments. In skinned cardiac or soleus skeletal muscle fibers but not in fibers from fast twitch skeletal muscle the kinetics of mitochondrial respiration regulation by ADP was characterized by very high apparent Km (low affinity) equal to 300-400 microM, exceeding that for isolated mitochondria by factor of 25. In skinned fibers from m. soleus, partial inhibition of respiration by NaN3 did not decrease the apparent Km for ADP significantly, this excluding the possible explanation of low apparent affinity of mitochondria to ADP in these cells by its rapid consumption due to high oxidative activity and by intracellular diffusion problems. However, short treatment of fibers with trypsin decreased this constant value to 40-70 microM, confirming the earlier proposition that mitochondrial sensitivity to ADP in vivo is controlled by some cytoplasmic protein. Phantom cardiomyocytes which contain mostly mitochondria and cytoskeleton and retain the normal shape, showed also high apparent Km values for ADP. Therefore, they are probably the most suitable system for studies of cellular factors which control mitochondrial function in the cells in vivo. In these phantom cells anti-desmin antibodies did not change the kinetics of respiration regulation by ADP. However, in skinned fibers from the heart and m. soleus of transgenic desmin-deficient mice some changes in kinetics of respiration regulation by ADP were observed: in these fibers two populations of mitochondria were observed, one with usually high apparent Km for ADP and the second one with very low apparent Km for ADP. Morphological observations by electron microscopy confirmed the existence of two distinct cellular populations in the muscle cells of desmin-deficient mice. The results conform to the conclusion that the reason for observed high apparent Km for ADP in regulation of oxidative phosphorylation in heart and slow twitch skeletal muscle cells in vivo is low permeability of mitochondrial outer membrane porins but not diffusion problems of ADP into and inside the cells. Most probably, in these cells there is a protein associated with cytoskeleton, which controls the permeability of the outer mitochondrial porin pores (VDAC) for ADP. Desmin itself does not display this type of control of mitochondrial porin pores, but its absence results in appearance of cells with disorganised structure and of altered mitochondrial population probably lacking this unknown VDAC controlling protein. Thus, there may be functional connection between mitochondria, cellular structural organisation and cytoskeleton in the cells in vivo due to the existence of still unidentified protein factor(s).

Adenosine Diphosphate↗
PubMed1997

Comparison of subcutaneous and intravenous administration of a solution of amino acids in older patients.

OBJECTIVE: To compare the plasma amino acid (AA) concentrations obtained by the infusion of an AA solution (660 mOsm/L, pH 7) using the subcutaneous (SC) with that using the intravenous (i.v.) route in older patients. DESIGN: A prospective, randomized, cross-over study. SETTING: A hospital geriatric ward. PARTICIPANTS: Six patients with a mean age of 84 years. MEASUREMENTS: The infusion of the AA solution (IV or SC) lasted 6 hours. Blood was sampled at 0, 2, 4, 6, 8, 10, 14, 18, and 24 hours from the start of the infusion to determine plasma AA level by the phenyl-isothiocyanate method. RESULTS: Compared with baseline values, plasma AA concentrations increased to a significantly higher level from the second to the tenth hour and from the second to the fourteenth hour during i.v. and SC infusions, respectively. Plasma AA levels did not differ between the two routes. SC infusion was well tolerated. CONCLUSION: Assuming that nutritional sufficiency is the desired result of plasma AA infusion, we conclude the SC route is well tolerated and offers the possibility of nitrogen supplementation for older patients over short periods of time, when oral protein intake is transiently insufficient or impossible, as a way to limit, but not to treat, protein-energy malnutrition.

Aged↗
PubMed1996

Action potentials in right and left ventricles from chronic hypoxic rats: effect of almitrine.

Rats were exposed to a 3-wk regimen of chronic normobaric hypoxia, with or without almitrine treatment. Chronic hypoxia led to a significant rise in the right ventricular mass and lengthened the action potential duration (APD) in right ventricle and in nonhypertrophied left ventricle. Hypertrophy and APD lengthening were significantly enhanced by almitrine. The classical acute hypoxia-induced shortening in APD was much larger in hypoxia-adapted hearts. In these hearts, almitrine treatment almost completely prevented such shortening, while the acute hypoxia-induced decrease in cardiac contraction was similar with or without almitrine. It is concluded that APD lengthening during chronic hypoxia can occur independently of ventricular hypertrophy. The similar directional effects of almitrine and chronic hypoxia on APD support the hypothesis of an energy-linked phenomenon. The dissociation of the almitrine effect on APD and contractility is in accordance with the view of a cellular energy compartmentation.

Action Potentials↗
PubMed1995

Correlation between degree of rupture of outer mitochondrial membrane and changes of kinetics of regulation of respiration by ADP in permeabilized heart and liver cells.

Kinetics of regulation of respiration by ADP in skinned cardiac fibers and permeabilized isolated hepatocytes was compared before and after mitochondrial swelling due to hypoosmotic treatment in 30-50 mOsM solutions. In both systems the apparent Km for ADP was high before mitochondrial swelling and equal to 297 +/- 35 microM and 275 +/- 35 microM, correspondingly. Hypoosmotic treatment resulted in the rupture of outer mitochondrial membrane and in the loss of exogenous cytochrome c, and both in skinned cardiac fibers and permeabilized hepatocytes the value of apparent Km for ADP was decreased in correlation with the extent of the rupture of the outer mitochondrial membrane. It is concluded that both in heart and liver cells in vivo, the ADP diffusion in the cells is retarded due to very low permeability of the outer mitochondrial membrane for ADP.

Adenosine Diphosphate↗