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X Leverve

Publications and source records attributed to X Leverve.

53 records · Page 3Linked to original sources

Splanchnic acid-base status and urea metabolism in uremic rats.

Acidosis may alter hepato-splanchnic amino acid metabolism during uremia.26 uremic rats and 30 controls were studied for portal and arterial acid-base balance and urea synthesis during enteral nutrition. Uremic rats exhibited increased (p < 0.05) portal H(+) (47.20 +/- 0.018 vs 43.05 +/- 0.49 nmol/I) and decreased HCO(3)(-) (19.45 +/- 0.69 vs 23.01 +/- 0.57 mmol/l) without significant change in arterial H(+) (45.29 +/- 1.13 vs 43.15 +/- 0.49) and HCO(3)(-) (18.41 +/- 0.64 vs 19.59 +/- 0.49). Porto-arterial difference showed an intestinal HCO(3)(-) release in controls only (3.53 +/- 0.64 mmol/l). Urea synthesis rate was significantly enhanced by enteral nutrition in controls only: 54.33 +/- 17.3 vs -11.8 +/- 20 micromol/min 100g body mass. Thus, during uremia, portal acidosis was associated with a decrease in enteral nutrition-induced urea synthesis.

Journal Article↗

Zinc changes in blood and urine during cyclic parenteral nutrition: relationships with amino acid metabolism.

Serum Zn, ultrafiltrable Zn and amino acids in serum and urine samples of twenty-seven patients receiving cyclic (12 h/24 h) parenteral nutrition were measured. These samples were collected in patients after a 12 h period of parenteral nutrition, and in the evening after 12 h without parenteral nutrition. The same determinations were performed in ten control subjects who followed the same sampling scheme. Total serum ultrafiltrable Zn showed no significant variations in the patients during parenteral nutrition, and was not significantly different in the two groups although the proportion of the Zn present in the ultrafiltrable fraction was elevated. Serum cystine levels were significantly higher (P = 0.05) in the patients than the control subjects, and cystine excretion was also higher in patients (P < 0.05) and increased after parenteral nutrition (56.0 (SE 6.5) v. 147.1 (SE 20.6) mumol/12 h; P < 0.001). Histidine levels did not vary significantly in serum after parenteral nutrition and were not different in the patients in comparison with the control subjects. Histidine excretion was not different in the two groups but increased significantly during parenteral nutrition (P < 0.05). Serum albumin was significantly depressed in the patients compared with the control subjects (45.3 (SE 1.5) v. 33.9 (SE 1.5) g/l; P < 0.001). These results suggest that cystine infusion and excretion relate to the changes occurring in serum Zn and in urinary Zn excretion.

Adolescent↗

Relationships between age-dependent changes in the effect of almitrine on H(+)-ATPase/ATPsynthase and the pattern of membrane fatty acid composition.

The effects of almitrine on ATPase/ATPsynthase previously described in beef heart mitochondria (Rigoulet et al. (1990) Biochim. Biophys. Acta 1018, 91-97) are also observed in liver mitochondria isolated from rats older than 7 weeks. In contrast, in rats younger than 5 weeks, almitrine at the same concentration has no effect on the ATPase/ATPsynthase complex. This age-dependent action of almitrine is well correlated with age-dependent modifications of two fatty acids: linoleic and docosahexaenoic acids. The possibility of a change in H+/ATP stoichiometry of the ATPase/ATPsynthase induced by almitrine seems related to more general modifications of membrane properties during growth of the rat.

Aging↗

[Should metabolic acidosis be alkalinized?].

At present, the administration of bicarbonate for metabolic acidosis has become controversial with regard to the indications and the modalities of treatment. Scientific evidence of the therapeutic value of bicarbonate is still lacking. In the opposite, there is a strong evidence of its adverse effects, such a paradoxical acidosis, sodium load and over all a worsening of haemodynamic status. Other therapeutic measures are limited. They include the administration of Carbicarb which does not increase the CO2 content, haemodialysis with bicarbonate and/or hyperventilation. As for every therapeutic action, the treatment must rely on an interpretation of the pathophysiological mechanism, resulting in the definition of therapeutic goals. The amendment of acidosis is not always a therapeutic priority. In ketoacidosis for instance, the depth of acidosis is mainly related to the degree of dehydration, the treatment of which results in a normalization of pH.

Acidosis↗

Flux-dependent increase in the stoichiometry of charge translocation by mitochondrial ATPase/ATP synthase induced by almitrine.

After studying the effects of almitrine, a new kind of ATPase/ATP synthase inhibitor, on two kinds of isolated mammalian mitochondrion, we have observed that: (1) Almitrine inhibits oligomycin-sensitive ATPase; it decreases the ATP/O value of oxidative phosphorylations without any change in the magnitude of delta mu H+. (2) Almitrine increases the mechanistic H+/ATP stoichiometry of ATPase as shown by measuring either (i) the extent of potassium acetate and of potassium phosphate accumulation sustained by ATP utilisation, or (ii) the electrical charge/ATP (K+/ATP) ratio at steady-state of ATPase activity. (3) Rat liver mitochondria are at least 10-times more sensitive to almitrine than beef heart mitochondria. (4) The change in H+/ATP stoichiometry induced by almitrine depends on the magnitude of the flux through ATPase. The inhibitory effect of almitrine on ATPase/ATP synthase complex, as a consequence of such an H+/ATP stoichiometry change, is discussed.

Acetates↗

Influence of the presence of a methyl group on the myocardial metabolism of 15-(paraiodophenyl)-3 methyl pentadecanoic acid (IMPPA).

The objective of the present study was to determine the mechanism of accumulation of myocardial activity following i.v. injection of 15-(paraiodophenyl)-3 methyl pentadecanoic acid (IMPPA). IMPPA and 15 phenyl-3 methyl pentadecanoic acid (MPPA) were labeled with 14C at position 1 and used to perfuse isolated rat hearts in a closed system. After 5 min of perfusion, IMPPA reached 2/3 of its value at 45 min. 14CO2 production was low. Most of the myocardial activity was in the form of free IMPPA. Analysis of IMPPA activation by CoA SH revealed that it was very strongly inhibited. The retention of myocardial activity is thus due to intracellular accumulation of free IMPPA following inhibition of activation. Comparison of results obtained with IMPPA and MPPA showed that the presence of iodine in the molecule accentuates the inhibition of activation.

Animals↗

Almitrine, a new kind of energy-transduction inhibitor acting on mitochondrial ATP synthase.

At low concentrations, almitrine inhibits yeast cell multiplication by acting on oxidative metabolism. Studies on isolated mitochondria display the following features: (i) almitrine inhibits ATPase activity and decreases ATP/O ratio during oxidative phosphorylation; (ii) no direct effect on respiration can be evidenced; (iii) ATP/O value decreases without any change in the magnitude of delta p; (iv) the higher the ATP synthesis and respiratory fluxes, the larger is the decrease in ATP/O ratio induced by almitrine. These results indicate that almitrine does not act as a classical protonophoric uncoupler nor as previously studied non protonophoric uncouplers (e.g., general anesthetics). Our data show a direct inhibitory effect of almitrine on ATPase-ATP synthase complex. But, in contrast to the classical inhibitors of this complex, almitrine decreases the ATP/O ratio in a flux-dependent manner. Thus, almitrine could induce either an intrinsic uncoupling of H+/-ATPase (i.e., slip in this proton pump) or a change in the mechanistic H+/ATP stoichiometry at the ATPase level.

Adenosine Triphosphate↗

Peripheral venous complications of a hyperosmolar (960 mOsm) nutritive mixture: The effect of heparin and hydrocortisone. A multicenter double-blinded random study in 98 patients.

Peripheral intravenous nutrition with hyperosmolar solutions usually results in a high rate of venous complications. The aim of this multicenter double blind randomised study in 98 patients has been to measure: (a) tolerance by the peripheral veins being perfused with a protein-glucose-lipid nutritive mixture of 960 mOsm/l (group A, n = 33), (b) the protective effect of the additive to the nutritive mixture of either heparin: 1000 IU/1 (group B, n = 32) or heparin with hydrocortisone (5 mg/l) group C, n = 33). Tolerance by the veins was evaluated on a single vein site during a 48 h perfusion with 21 per day. The following complications: oedema, erythema, induration, thrombophlebitis led to the interruption of the perfusion. The rate of interruptions of perfusions for total venous complications and for thrombophlebitis has been respectively: at 24 h, in group A: 39 and 15%, in group B: 6 and 3%, in group C: 12 and 0%; at 48 h: in group A: 82 and 42%, in group B: 53 and 18%, in group C: 36 and 6%. Venous complication rates for 24 and 48 h were significantly lower in groups B and C (p<0.05) than in group A and there was no inter group difference between groups B and C. These results suggest that peripheral venous nutrition infusing 14.1 g of nitrogen and 8.5 MJ per day can be performed with a hyperosmolar solution of 960 mOsm/1, if that heparin be added to the nutritive mixture and the perfusion site be changed daily. Under these conditions the observed venous complications rate is equal to or less than 6% of cases.

Journal Article↗

Effect of parenteral nutrition on muscle amino acid output and 3-methylhistidine excretion in septic patients.

The effects of adequate total parenteral nutrition (TPN) on nitrogen excretion, urea N percentage, 3-methylhistidine excretion, and leg amino acid output, were studied during the ten-day period following abdominal surgery for generalized peritonitis in nine patients. The first two postoperative days were without nutritional intake, TPN was started on the third postoperative day (57 cal/KgBW--40% as Intralipid--0.30 g of N/KgBW). Leg amino acid outputs were done before TPN (DO), then two days (D2) and eight days (D8) after TPN. Total nitrogen and urea N percentage did not significantly differ before and after TPN. Between DO and D2 there was a significant reduction of urinary 3-methylhistidine (467 +/- 37 to 280 +/- 29 mumol/24 h-P less than 0.001) and leg amino acid release (604 +/- 103 to 254 +/- 87 nmol/mn/100 g of calf muscle--P less than 0.01) reflecting reduction in muscle hypercatabolism despite the persistence of the septic state. Between D2 and D8, 3-methylhistidine remained stable while leg amino acid release continued to decrease (254 +/- 87 to 68 +/- 40 nmol/mn/100 g--P less than 0.05). This association suggests an increased muscle protein synthesis. A closer examination of the clinical evolution of these patients, especially concerning their septic evolution, shows that only improved patients with recovery from sepsis increased their muscle protein synthesis. Thus, in septic hypercatabolic patients TPN seems to be able to reduce muscle catabolism while the increase in protein synthesis is mainly the consequence of recovery from the septic state. In such patients TPN should be used as a preventive therapeutic measure.

Adult↗

On the regulation of cellular energetics in health and disease.

Very recent experimental data, obtained by using the permeabilized cell technique or tissue homogenates for investigation of the mechanisms of regulation of respiration in the cells in vivo, are shortly summarized. In these studies, surprisingly high values of apparent Km for ADP, exceeding that for isolated mitochondria in vitro by more than order of magnitude, were recorded for heart, slow twitch skeletal muscle, hepatocytes, brain tissue homogenates but not for fast twitch skeletal muscle. Mitochondrial swelling in the hypo-osmotic medium resulted in the sharp decrease of the value of Km for ADP in correlation with the degree of rupture of mitochondrial outer membrane, as determined by the cytochrome c test. Very similar effect was observed when trypsin was used for treatment of skinned fibers, permeabilized cells or homogenates. It is concluded that, in many but not all types of cells, the permeability of the mitochondria outer membrane for ADP is controlled by some cytoplasmic protein factor(s). Since colchicine and taxol were not found to change high values of the apparent Km for ADP, the participation of microtubular system seems to be excluded in this kind of control or respiration but studies of the roles of other cytoskeletal structures seem to be of high interest. In acute ischemia we observed rapid increase of the permeability of the mitochondrial outer membrane for ADP due to mitochondrial swelling and concomitant loss of creatine control of respiration as a result of dissociation of creatine kinase from the inner mitochondrial membrane. The extent of these damages was decreased by use of proper procedures of myocardial protection showing that outer mitochondrial membrane permeability and creatine control of respiration are valuable indices of myocardial preservation. In contrast to acute ischemia, chronic hypoxia seems to improve the cardiac cell energetics as seen from better postischemic recovery of phosphocreatine, and phosphocreatine overshoot after inotropic stimulation. In general, adaptational possibilities and pathophysiological changes in the mitochondrial outer membrane system point to the central role such a system may play in regulation of cellular energetics in vivo.

Adenosine Diphosphate↗

Acidosis and nutritional status in hemodialyzed patients. French Study Group for Nutrition in Dialysis.

In a cross-sectional study of more than 30% of French dialysis patients (N = 7,123), we evaluated the relationships between predialysis plasma bicarbonate concentration and nutritional markers. Data including age, gender, cause of end-stage renal disease (ESRD), time on dialysis, body mass index (BMI), blood levels of midweek predialysis albumin, prealbumin, and bicarbonate were collected. Normalized protein catabolic rate (nPCR), dialysis adequacy parameters, and estimation of lean body mass (LBM) were computed from pre- and postbicarbonate-dialysis urea and creatinine levels according to the classical formulas of Garred. Average values (+/- 1 SD) were age 61 +/- 16 years, BMI 23.3 +/- 4.6 kg/m2, dialysis time 12.4 +/- 2.7 h/week, HCO3 22.8 +/- 3.5 mmol/L, albumin 38.7 +/- 5.3 g/L, prealbumin 340 +/- 90 mg/L, Kt/V 1.36 +/- 0.36, nPCR 1.13 +/- 0.32 g/kg BW/day, and LBM 0.86 +/- 0.21% of ideal LBM. A highly significant negative correlation was observed between predialysis bicarbonate levels (within a range of 16-30 mmol/L, 95% of this population) and nPCR confirmed by analysis of variance using bicarbonate classes (p < 0.0001). Bicarbonate was also negatively correlated with albumin, prealbumin, BMI, and LBM. No relationship was noted between bicarbonate and Kt/V despite a positive correlation between Kt/V and nPCR. It is likely that a persistent acidosis observed despite standard bicarbonate dialysis was caused by a high dietary protein intake which results in an increased acid load, but also overcomes the usual catabolic effects of acidosis.

Acidosis↗

Muscle protein degradation in severely malnourished patients with chronic obstructive pulmonary disease subject to short-term total parenteral nutrition.

Patients with chronic obstructive pulmonary disease (COPD) often lose weight and muscle mass with progression of the disease. Muscle protein degradation in patients with COPD has never been examined before and during hypercaloric feeding. Eight severely malnourished patients with COPD were examined at home consuming their usual intake, in the hospital after 3 days of a meat-free regular oral diet (period B), and during a hypercaloric (55 kcal/kg) high-lipid (55%) parenteral formula (total parenteral nutrition [TPN]). During period B, 8 well-nourished patients and 10 malnourished cancer patients were used as control groups. Measurements included plasma assays, leg blood flow, leg exchange (of 3-methylhistidine [3MeH], glucose, lactate, and oxygen) and urinary measures of 3MeH, creatinine, and nitrogen. During period B, net release of 3MeH across the leg in patients with COPD was similar to that in well-nourished control subjects and cachectic cancer patients. In COPD patients, there was only a transient decrease in leg exchange values of 3MeH with administration of TPN. COPD patients demonstrated a reduction (p less than .01) in urinary 3MeH excretion and an increase in nitrogen balance (p less than .01) with TPN compared with period B. The decrease in muscle protein degradation with administration of TPN accounts for about 50% of the increase in nitrogen retention in patients with COPD. These data suggest that in severely malnourished patients with COPD the weight loss is not dependent on increased rates of skeletal muscle protein degradation; nevertheless, degradation rates attenuate with a positive nitrogen balance during nutrition repletion.

Aged↗

Effect of parenteral medium- and long-chain triglycerides on lymphocytes subpopulations and functions in patients with acquired immunodeficiency syndrome: a prospective study.

BACKGROUND: Total parenteral nutrition (TPN) may offer significant clinical benefit in malnourished patients with acquired immunodeficiency syndrome (AIDS). However, the immunologic effect of parenteral lipids remains unknown in these severely immunodepressed patients. METHODS: We undertook a prospective randomized double-blind multicenter study comparing the effects of two i.v. lipid emulsions used during TPN: long-chain triglycerides (LCT) or balanced emulsion of long-and medium-chain triglycerides (LCT/MCT). Thirty-three AIDS patients requiring TPN for wasting and reduced oral intake were allocated randomly to receive a ternary TPN mixture consisting of 1.5 g/kg/d proteins, 18 kcal/kg/d lipids, and 12 Kcal/kg/d carbohydrates for 6 days. The following tests were performed at days 0 and 7: immunoglobulins, complement fractions, lymphocyte subpopulations count, and lymphocyte proliferation with mitogens. RESULTS: Patients were all severely malnourished (weight loss: -14.0 +/- 1.3 kg). No clinical or biological differences were observed between the groups at baseline. At day 7, both groups reported a significant increase in weight. Patients in the LCT group exhibited a significant decrease in phytohemagglutinin A response (p = .04) compared with baseline. Patients in the LCT/MCT group exhibited a lower level of IgM (p = .03) and significant increase in C3 fraction (p = .03) compared with baseline. They also showed a tendency to have a higher CD4/CD8 lymphocyte ratio (p = .07), whereas other immunological parameters remained unchanged CONCLUSIONS: Parenteral ternary mixture containing LCT or LCT/MCT are clinically well tolerated in AIDS patients over 6 days. With 2 g/kg/d of lipids, LCT seems to induce significant abnormalities in lymphocyte function. Such abnormalities are not observed with LCT/MCT.

Acquired Immunodeficiency Syndrome↗

Cellular physiology and molecular events in hypoxia-induced apoptosis.

Malignant tumors contain a significant fraction of microregions that are chronically or transiently hypoxic. The experimental evidence showing that hypoxia may have a profound impact on malignant progression and on responsiveness to therapy is growing. In fact hypoxia, like other genotoxic and non-genotoxic stresses, has been shown to increase the p53 protein level, and subsequently activate target genes like p21/waf-1 which interact with cell cycle machinery or participate in apoptosis. Apoptosis is a genetically encoded program of cell death that can be activated under physiological conditions like hypoxia, and may be an important safeguard against tumour development. One of the first common manifestations of the apoptotic process, irrespective of the cell type, is the disruption of mitochondrial membrane function, including a dissipation of the delta psi m and/or a modification on the mitochondrial release of protease activators. These modifications are linked to specific patterns of bioenergetic parameters i.e. respiratory flux, mitochondrial redox potential and phosphate potential. We have studied gluconeogenesis and glycolysis pathways in intact hepatocytes isolated from fasted rats submitted to 24 h of hypoxic in vivo exposure. We have shown that hypoxia resulted in an inhibition of the gluconeogenesis pathway due to a decrease in phosphoenolpyruvate carboxykinase (PEPCK) activity and mRNA synthesis in rat hepatocytes. In conclusion, the disruption of mitochondrial membrane function in response to different oxygen content such as periarterial or perivenous PO2 led to the inhibition of gluconeogenesis and apoptosis in hypoxic cells.

Animals↗