Biomedical subjects

X Leverve

Publications and source records attributed to X Leverve.

At least 19 recordsLinked to original sources

PubMed2006

High dietary sucrose triggers hyperinsulinemia, increases myocardial beta-oxidation, reduces glycolytic flux and delays post-ischemic contractile recovery.

Although the causal relationship between insulin resistance (IR) and hypertension is not fully resolved, the importance of IR in cardiovascular dysfunction is recognized. As IR may follow excess sucrose or fructose diet, the aim of this study was to test whether dietary starch substitution with sucrose results in myocardial dysfunction in energy substrate utilization and contractility during normoxic and post-ischemic conditions. Forty-eight male Wistar rats were randomly allocated to three diets, differing only in their starch to sucrose (S) ratio (13, 2 and 0 for the Low S, Middle S and High S groups, respectively), for 3 weeks. Developed pressure and rate x pressure product (RPP) were determined in Langendorff mode-perfused hearts. After 30 min stabilization, hearts were subjected to 25 min of total normothermic global ischemia, followed by 45-min reperfusion. Oxygen consumption, beta-oxidation rate (using 1-13C hexanoate and Isotopic Ratio Mass Spectrometry of CO2 produced in the coronary effluent) and flux of non-oxidative glycolysis were also evaluated. Although fasting plasma glucose levels were not affected by increased dietary sucrose, high sucrose intake resulted in increased plasma insulin levels, without significant rise in plasma triglyceride and free fatty acid concentrations. Sucrose-rich diet reduced pre-ischemic baseline measures of heart rate, RPP and non-oxidative glycolysis. During reperfusion, post-ischemic recovery of RPP was impaired in the Middle S and High S groups, as compared to Low S, mainly due to delayed recovery of developed pressure, which by 45 min of reperfusion eventually resumed levels matching Low S. At the start of reperfusion, delayed post-ischemic recovery of contractile function was accompanied by: (i) reduced lactate production; (ii) decreased lactate to pyruvate ratio; (iii) increased beta-oxidation; and (iv) depressed metabolic efficiency. In conclusion, sucrose rich-diet increased plasma insulin levels, in intact rat, and increased cardiac beta-oxidation and coronary flow-rate, but reduced glycolytic flux and contractility during normoxic baseline function of isolated perfused hearts. Sucrose rich-diet impaired early post-ischemic recovery of isolated heart cardiac mechanical function and further augmented cardiac beta-oxidation but reduced glycolytic and lactate flux.

Animals↗

PubMed2006

Effects of permeability transition inhibition and decrease in cytochrome c content on doxorubicin toxicity in K562 cells.

As mitochondria play a key role in the commitment to cell death, we have investigated the mitochondrial consequences of resistance to doxorubicin (DOX) in K562 cells. We found that the permeability transition pore (PTP) inhibitor cyclosporine A (CsA) failed to inhibit PTP opening in the resistant clone. Moreover, the Ca2+ loading capacity in the resistant clone was identical to that observed in the parent cells in the presence of CsA, suggesting that the PTP was already inhibited in a CsA-like manner in the resistant cells. In agreement with this proposal, the mitochondrial target of CsA cyclophilin D (CyD) decreased by half in the resistant cells. The levels of adenine nucleotide translocator, voltage anion-dependent channel, Bax, Bcl-2, Bcl-xL, AIF and Smac/Diablo, were similar in both cell lines, whereas cytochrome c content was divided by three in the resistant cells. Since P-glycoprotein inhibition did not restore DOX toxicity in the resistant cells, while DOX-induced cell death in the parent cells was prevented by either PTP inhibition or siRNA-induced decrease in cytochrome c content, we conclude that the inhibition of PTP opening and the decrease in cytochrome c content participate in the mechanism that makes K562 cells resistant to DOX.

Antibiotics, Antineoplastic↗

PubMed2003

Low rate of glucose 6-phosphate hydrolysis in liver cells is a physiological feature of non-diabetic wild sand rats (Psammomys obesus).

OBJECTIVE: In this study we have compared glucose metabolism and liver gluconeogenesis in wild adult desert gerbil Psammomys obesus fed with their natural halophilic plants and Wistar rats fed on a laboratory chow. Psammomys obesus is a natural model of insulin resistance when fed a rodent laboratory chow. METHODS: Basal glucose and insulin were determined in plasma of fasting animals. Hepatocyte gluconeogenesis from lactate-plus-pyruvate was investigated in perifused hepatocytes by assessing simultaneously glucose synthesis rate and intracellular oxaloacetate, phosphoenolpyruvate, 3-phosphoglycerate, fructose 6-phosphate and glucose 6-phosphate (G6P) under true steady state conditions. RESULTS: Fasting blood glucose (2.8 +/- 0.1 vs 4.8 +/- 0.4 mmol.L(- 1)) and plasma insulin concentration (129 +/- 14 vs 150 +/- 21 pmol.L(-1)) were significantly lower in Psammomys as compared to albino rats. Maximal gluconeogenic rate was also lower in Psammomys (2.3 +/- 0.3 vs 5.1 +/- 0.3 micromol x min(-1) x g dry cells(-1)). This effect was related to a slower hydrolysis of G6P. CONCLUSION: A lower G6P hydrolysis in Psammomys as compared to wistar was the main difference between the two groups of liver cells. Such feature may represent the major metabolic adaptation permitting Psammomys to survive despite its severe restrictive natural conditions. Indeed, a low G6P hydrolysis allows an insulin resistance state, with a high lipogenic activity, but associated with low blood glucose. The rise in blood glucose occurring when Psammomys are fed with exogenous carbohydrates perturbs such delicate metabolic equilibrium, resulting thus in a diabetic state because of the deleterious effect of hyperglycemia.

Animals↗

PubMed2002

Protective effects of recombinant growth hormone on intestinal mucosa in rats receiving abdominal radiotherapy.

BACKGROUND AND AIMS: Radiation injury to the gut induces nutrient losses that compromise the body ability to adequately fight infection, heal wounds and recover from illness. Recombinant growth hormone (rhGH), is known to enhance anabolism, therefore, we tested the hypothesis that rhGH preserves whole body growth and trophism of the jejunum and ileum of irradiated rats. METHODS: After acclimatization period, the rats were divided in three groups: (1). control rats (C), (2). rats irradiated with a single dose of 10 Gy (group A); (3). rats irradiated with a single dose of 5 Gy (Group B); after irradiation, rats were given subcutaneously (sc) saline or 0.25 or 0.50 mg rhGH/kg BW/d for the following 6 days. Body weight changes were recorded during this time. On day 6 post-radiation, rats were killed and small intestine mucosa dry and wet weights were measured, as well as mucosa protein content. RESULTS: Group A rats lost body weight during the 6-day post-radiation period, regardless of rhGH treatment and dosage. rhGH was effective in preventing weight loss and normalizing growth in group B rats (saline 23.1+/-11.1, vs. controls P<0.05; rhGH: 35.0+/-10.0 g BW/d, vs. controls P = ns). Trophic effect of rhGH was observed on mucosa weight and mucosa protein content in rats irradiated with 5 Gy, but not in those receiving 10 Gy. CONCLUSION: rhGH seems to normalize growth and mucosa protein content in irradiated rats. However, rhGH beneficial effects were observed only in rats receiving the lower dose of radiation.

Animals↗

PubMed2001

Rotenone inhibits the mitochondrial permeability transition-induced cell death in U937 and KB cells.

The permeability transition pore (PTP) is a mitochondrial inner membrane Ca(2+)-sensitive channel that plays a key role in different models of cell death. Because functional links between the PTP and the respiratory chain complex I have been reported, we have investigated the effects of rotenone on PTP regulation in U937 and KB cells. We show that rotenone was more potent than cyclosporin A at inhibiting Ca(2+)-induced PTP opening in digitonin-permeabilized cells energized with succinate. Consistent with PTP regulation by electron flux through complex I, the effect of rotenone persisted after oxidation of pyridine nucleotides by duroquinone. tert-butyl hydroperoxide induced PTP opening in intact cells (as shown by mitochondrial permeabilization to calcein and cobalt), as well as cytochrome c release and cell death. All these events were prevented by rotenone or cyclosporin A. These data demonstrate that respiratory chain complex I plays a key role in PTP regulation in vivo and confirm the importance of PTP opening in the commitment to cell death.

Cell Death↗

PubMed2001

The mitochondrial consequences of uncoupling intact cells depend on the nature of the exogenous substrate.

In isolated mitochondria the consequences of oxidative phosphorylation uncoupling are well defined, whereas in intact cells various effects have been described. Uncoupling liver cells with 2,4-dinitrophenol (DNP) in the presence of dihydroxyacetone (DHA) and ethanol results in a marked decrease in mitochondrial transmembrane electrical potential (DeltaPsi), ATP/ADP ratios and gluconeogenesis (as an ATP-utilizing process), whereas the increased oxidation rate is limited and transient. Conversely, when DHA is associated with octanoate or proline, DNP addition results in a very large and sustained increase in oxidation rate, whereas the decreases in DeltaPsi, ATP/ADP ratios and gluconeogenesis are significantly less when compared with DHA and ethanol. Hence significant energy wastage (high oxidation rate) by uncoupling is achieved only with substrates that are directly oxidized in the mitochondrial matrix. Conversely in the presence of substrates that are first oxidized in the cytosol, uncoupling results in a profound decrease in mitochondrial DeltaPsi and ATP synthesis, whereas energy wastage is very limited.

Adenosine Diphosphate↗

PubMed2001

Acute hepatic steatosis complicating massive insulin overdose and excessive glucose administration.

OBJECTIVE: To describe a case of acute hepatic steatosis due to excessive administration of glucose in the setting of massive insulin overdose, a complication which is rapidly and completely reversible if glucose infusion is rapidly tapered. DESIGN: Case report, clinical. SETTING: Intensive care unit, university hospital. PATIENT: A single patient admitted to the ICU. INTERVENTION: Intravenous glucose after insulin overdose. MEASUREMENTS AND MAIN RESULTS: On the 3rd day, increases in transaminase (ASAT 420 IU/l, ALAT 610 IU/l), bilirubin (147 mmol/l) and lactate (6.8 mmol/l), a decrease in arterial pH (7.32) and slightly increased liver size on ultrasound examination suggested acute hepatic steatosis. Clinical and laboratory abnormalities resolved rapidly after discontinuation of excessive glucose infusions (1,400 g/day for 3 days). CONCLUSIONS: Very large amounts of glucose after massive insulin overdose are potentially dangerous. Even though the fear of hypoglycemia-induced neurologic damage should be a constant preoccupation in this situation, glucose administration should be titrated on closely monitored blood glucose levels.

Acidosis, Lactic↗

PubMed2001

Factors influencing survival in hemodialysis patients aged older than 75 years: 2.5-year outcome study.

The incidence of malnutrition is widely held to be greater in the elderly, but this specific factor has not been extensively studied in elderly dialysis patients. In a 30-month follow-up prospective study, we evaluated the role of nutrition on the outcome of 290 stable hemodialysis (HD) outpatients aged older than 75 years followed up in 20 French HD centers (167 men, 123 women; age, 79.8 +/- 4.2 years; previous time on dialysis, 41 +/- 38 months). On the same day in January 1996, predialysis and postdialysis blood samples were collected according to recommended procedures for dialysis quantification. Normalized protein catabolic rate, dialysis adequacy parameters, and estimation of lean body mass (LBM; expressed as observed/expected LBM values [obs/exp LBM]) were computed from predialysis and postdialysis urea and creatinine levels. Overall survival rates were 80% and 65% after 1 and 2 years of follow-up, respectively, and were significantly less in patients with the lower quartile of obs/exp LBM. In univariate analysis using the Cox proportional hazards model, survival was significantly influenced by age, albumin level, prealbumin level, body mass index, and diabetes, but not by sex, Kt/V, duration of dialysis, cholesterol level, hemoglobin level, or obs/exp LBM. In multivariate analysis, no variable remained significant. Cardiovascular mortality accounted for 52.1% of the patient deaths. We conclude that in elderly HD patients, malnutrition influences overall survival despite adequate dialysis treatment.

Aged↗

PubMed2001

Metabolic and nutritional disorders in cardiac cachexia.

Cardiac cachexia is divided into two types, i.e., the classic type, which occurs in patients with severe heart failure, and the nosocomial type, which develops in the postoperative state. Cardiac cachexia is due both to a decrease in nutrient intake (anorexia, malabsorption) and to specific metabolic alterations (hypercatabolism with increased energy expenditure, response to hypoxia, inflammatory status, etc). Among the various mechanisms involved in the pathogenesis of cachexia, cellular hypoxia has long been recognized. The chronic activation of the endogenous neurohormonal system is another specific feature of such patients; a striking relationship was found between cardiac cachexia and hormonal levels which correlate better than the classical parameters of cardiac failure severity. Finally, inflammatory syndrome has been known to occur frequently in patients with cardiac cachexia. Several studies have shown that tumor necrosis factor-alpha was significantly increased in cachectic patients and that chronic activation of the systemic immune response might be a common and unifying factor.

Cachexia↗

PubMed2001

Allosteric activation of pyruvate kinase via NAD+ in rat liver cells.

In isolated rat hepatocytes, it has previously been reported that a rise in the ATP content induces a proportional increase in cytosolic NAD+ concentration [Devin, A., Guérin, B. & Rigoulet, M. (1997) FEBS Lett. 410, 329-332]. This occurs under physiological conditions such as various substrates or different energetic states. To investigate the effect of a physiological rise in cytosolic [NAD+] per se on glycolysis and gluconeogenesis, an increase in [NAD+] induced by exogenous nicotinamide addition was obtained without a change in redox potential, ATP/ADP ratio and ATP concentration. Using dihydroxyacetone as substrate, we found that an increase in cytosolic [NAD+] decreases gluconeogenesis and enhances glycolysis without significant alteration of dihydroxyacetone consumption rate. These modifications are the consequence of an allosteric activation of pyruvate kinase via cytosolic NAD+ content. Thus, in addition to the well-known thermodynamic control of glycolysis by pyridine-nucleotide redox status, our study points to a new mechanism of glycolytic flux regulation by NAD+ concentration at the level of pyruvate kinase activity.

Adenosine Diphosphate↗

PubMed2001

Influence of nutritional factors and hemodialysis adequacy on the survival of 1,610 French patients.

Nutritional factors and dialysis adequacy are associated with outcome in hemodialyzed patients, but their relative contribution remains controversial, particularly when dialysis adequacy complies with current recommendations (Kt/V >1.2). Survival, clinical, and nutritional data from a cohort of prevalent 1,610 patients treated by hemodialysis in 20 centers in France have been collected over a 2.5-year period, from January 1996 to July 1998. Data including age, sex, cause of end-stage renal disease (ESRD), clinical outcome, time on dialysis, body mass index (BMI), blood levels of midweek predialysis albumin, prealbumin, and bicarbonate were analyzed. Normalized protein catabolic rate (nPCR), dialysis adequacy parameters, and estimation of lean body mass (LBM) from creatinine generation were computed from pre- and postdialysis urea and creatinine levels. The characteristics of the patients were as follows: age 59.6 +/- 16.5 years, 58.8% males, 11% of diabetics, time on dialysis 63.2 +/- 64.5 m. Weekly dialysis time was 12.18 +/- 1.78 hrs, Kt/V 1.34 +/- 0.34, nPCR 1.10 +/- 0.35 g/kg body weight/day. Albumin concentration was 39.4 +/- 5.3 g/L, prealbumin was 0.33 +/- 0.09 g/L, BMI was 23.0 +/- 4.5 kg/m(2). Overall survival was 89.7% +/- 0.8% and 78.4% +/- 1.1% after 1 and 2 years. In the Cox proportional hazard model, survival was significantly influenced by age, the presence of diabetes, and by concentrations of albumin and prealbumin, but not by other variables, including Kt/V and urea reduction ratio. These results indicate that nutritional protein concentrations were predictive of dialysis outcome, whereas variables reflecting actual body composition and dialysis dose were not. Furthermore, in this well-dialyzed population, dialysis adequacy had no influence on survival. In conclusion, when adequacy targets are met in hemodialyzed patients, survival is mainly dependent on age and nutritional status. Efforts should be focused on the most efficient ways to maintain nutritional status in these patients.

Adult↗

PubMed2001

Role of Na+-K+-ATPase in insulin-induced lactate release by skeletal muscle.

Hyperinsulinemia increases lactate release by various organs and tissues. Whereas it has been shown that aerobic glycolysis is linked to Na+-K+-ATPase activity, we hypothesized that stimulation by insulin of skeletal muscle Na+-K+-ATPase is responsible for increased muscle lactate production. To test this hypothesis, we assessed muscle lactate release in healthy volunteers from the [13C]lactate concentration in the effluent dialysates of microdialysis probes inserted into the tibialis anterior muscles on both sides and infused with solutions containing 5 mmol/l [U-13C]glucose. On one side, the microdialysis probe was intermittently infused with the same solution additioned with 2.10(-5) M ouabain. In the basal state, [13C]lactate concentration in the dialysate was not affected by ouabain. During a euglycemic-hyperinsulinemic clamp, [13C]lactate concentration increased by 135% in the dialysate without ouabain, and this stimulation was nearly entirely reversed by ouabain (56% inhibition compared with values in the dialysate collected from the contralateral probe). These data indicate that insulin stimulates muscle lactate release by activating Na+-K+-ATPase in healthy humans.

Adult↗

PubMed2000

Three classes of ubiquinone analogs regulate the mitochondrial permeability transition pore through a common site.

To identify the structural features required for regulation of the mitochondrial permeability transition pore (PTP) by ubiquinone analogs (Fontaine, E., Ichas, F., and Bernardi, P. (1998) J. Biol. Chem. 40, 25734-25740), we have carried out an analysis with quinone structural variants. We show that three functional classes can be defined: (i) PTP inhibitors (ubiquinone 0, decylubiquinone, ubiquinone 10, 2,3-dimethyl-6-decyl-1,4-benzoquinone, and 2,3,5-trimethyl-6-geranyl-1,4-benzoquinone); (ii) PTP inducers (2,3-dimethoxy-5-methyl-6-(10-hydroxydecyl)-1,4-benzoquinone and 2,5-dihydroxy-6-undecyl-1,4-benzoquinone); and (iii) PTP-inactive quinones that counteract the effects of both inhibitors and inducers (ubiquinone 5 and 2,3,5-trimethyl-6-(3-hydroxyisoamyl)-1,4-benzoquinone) . The structure-function correlation indicates that minor modifications in the isoprenoid side chain can turn an inhibitor into an activator, and that the methoxy groups are not essential for the effects of quinones on the PTP. Since the ubiquinone analogs used in this study have a similar midpoint potential and decrease mitochondrial production of reactive oxygen species to the same extent, these results support the hypothesis that quinones modulate the PTP through a common binding site rather than through oxidation-reduction reactions. Occupancy of this site can modulate the PTP open-closed transitions, possibly through secondary changes of the PTP Ca(2+) binding affinity.

Animals↗

PubMed2000

Dimethylbiguanide inhibits cell respiration via an indirect effect targeted on the respiratory chain complex I.

We report here a new mitochondrial regulation occurring only in intact cells. We have investigated the effects of dimethylbiguanide on isolated rat hepatocytes, permeabilized hepatocytes, and isolated liver mitochondria. Addition of dimethylbiguanide decreased oxygen consumption and mitochondrial membrane potential only in intact cells but not in permeabilized hepatocytes or isolated mitochondria. Permeabilized hepatocytes after dimethylbiguanide exposure and mitochondria isolated from dimethylbiguanide pretreated livers or animals were characterized by a significant inhibition of oxygen consumption with complex I substrates (glutamate and malate) but not with complex II (succinate) or complex IV (N,N,N',N'-tetramethyl-1, 4-phenylenediamine dihydrochloride (TMPD)/ascorbate) substrates. Studies using functionally isolated complex I obtained from mitochondria isolated from dimethylbiguanide-pretreated livers or rats further confirmed that dimethylbiguanide action was located on the respiratory chain complex I. The dimethylbiguanide effect was temperature-dependent, oxygen consumption decreasing by 50, 20, and 0% at 37, 25, and 15 degrees C, respectively. This effect was not affected by insulin-signaling pathway inhibitors, nitric oxide precursor or inhibitors, oxygen radical scavengers, ceramide synthesis inhibitors, or chelation of intra- or extracellular Ca(2+). Because it is established that dimethylbiguanide is not metabolized, these results suggest the existence of a new cell-signaling pathway targeted to the respiratory chain complex I with a persistent effect after cessation of the signaling process.

Animals↗

PubMed2000

Prevalence and consequences of nutritional depletion in lung transplant candidates.

Nutritional status was studied in lung transplant (LT) candidates. The hypotheses were that nutritional depletion was highly prevalent and lean body mass depletion was a risk factor for a higher mortality both before and after LT. Of 78 consecutive patients listed for LT, 16 (21%) died while on the waiting list, eight (10%) were alive awaiting LT, and 54 (69%) received a graft. Mean age was 42.3+/-4.4 (mean+/-SD). Thirty-eight per cent had a diagnosis of bronchiectasis or cystic fibrosis (BRO/CF), 33% of emphysema, 20% of idiopathic pulmonary fibrosis (IPF) and 8% of primary pulmonary hypertension. Body mass index (BMI) was 20.4+/-4.3 kg.m2, weight was 87.9+/-16.6% of ideal body weight (IBW). Patients were classed into four nutritional groups according to IBW and creatinine height index (CHI): 1: weight <90% IBW and CHI <60% of predicted (28% of cases); II: weight <90% IBW and CHI > or =60% (27%); III: weight > or =90% IBW and CHI <60% (17%); IV: weight > or =90% IBW and CHI > or =60% (28%). Overall, 72% were depleted corresponding to groups 1, II and III. Lean body mass depletion occurred despite normal weight in 17% of the cases (group III). Subjects with BRO/CF were mostly in groups 1, II, III whereas IPF were concentrated in group II. Lean body mass depletion was associated with more severe hypoxaemia, reduced 6-minute walking distance and a higher mortality while awaiting. After LT, duration of mechanical ventilation, time spent in intensive care unit (ICU) was related to initial body composition. Survival after LT was lowest in group III. To conclude, nutritional depletion in lung transplant candidates is highly prevalent and should be more precisely assessed with a special reference to lean body mass since it has specific consequences both while awaiting and after lung transplant. Attempts should be made to increase lean body mass before lung transplant.

Adult↗

PubMed2000

Effects of cardiogenic shock on lactate and glucose metabolism after heart surgery.

BACKGROUND: Hyperlactatemia is a prominent feature of cardiogenic shock. It can be attributed to increased tissue production of lactate related to dysoxia and to impaired utilization of lactate caused by liver and tissue underperfusion. The aim of this prospective observational study was to determine the relative importance of these mechanisms during cardiogenic shock. PATIENTS: Two groups of subjects were compared: seven cardiac surgery patients with postoperative cardiogenic shock and seven healthy volunteers. METHODS: Lactate metabolism was assessed by using two independent methods: a) a pharmacokinetic approach based on lactate plasma level decay after the infusion of 2.5 mmol x kg(-1) of sodium lactate; and b) an isotope dilution technique for which the transformation of [13C]lactate into [13C]glucose and 13CO2 was measured. Glucose turnover was determined using 6,62H2-glucose. RESULTS: All patients suffered from profound shock requiring high doses of inotropes and vasopressors. Mean arterial lactate amounted to 7.8 +/- 3.4 mmol x L(-1) and mean pH to 7.25 +/- 0.07. Lactate clearance was not different in the patients and controls (7.8 +/- 3.4 vs. 10.3 +/- 2.1 mL x kg(-1) x min(-1)). By contrast, lactate production was markedly enhanced in the patients (33.6 +/- 16.4 vs. 9.6 +/- 2.2 micromol x kg(-1) x min(-1); p < .01). Exogenous [13C]lactate oxidation was not different (107 +/- 37 vs. 103 +/- 4 mmol), and transformation of [13C]lactate into [13C]glucose was not different (20.0 +/- 13.7 vs. 15.2% +/- 6.0% of exogenous lactate). Endogenous glucose production was markedly increased in the patients (1.95 +/- 0.26 vs. 5.3 +/- 3.0 mg x kg(-1) x min(-1); p < .05 [10.8 +/- 1.4 vs. 29.4 +/- 16.7 micromol x kg(-1) x min(-1)]), whereas net carbohydrate oxidation was not different (1.7 +/- 0.5 vs. 1.3 +/- 0.3 mg x kg(-1) x min(-1) [9.4 +/- 2.8 vs. 7.2 +/- 1.7 micromol x kg(-1) x min(-1)]). CONCLUSIONS: Hyperlactatemia in early postoperative cardiogenic shock was mainly related to increased tissue lactate production, whereas alterations of lactate utilization played only a minor role. Patients had hyperglycemia and increased nonoxidative glucose disposal, suggesting that glucose-induced stimulation of tissue glucose uptake and glycolysis may contribute significantly to hyperlactatemia.

Acidosis, Lactic↗

PubMed2000

Mechanisms of increased gluconeogenesis from alanine in rat isolated hepatocytes after endurance training.

This work aimed at further investigating the mechanisms by which liver gluconeogenic capacity from alanine is improved after training in rats, with an isolated hepatocyte model. Compared with controls in hepatocytes from trained rats incubated with gluconeogenic precursors (20 mM), the glucogenic flux (J(glucose)) was increased by 64% from alanine (vs. 21% for glycerol, 18% for lactate-pyruvate 10:1, and 10% for dihydroxyacetone). Maximal intracellular alanine accumulation capacity was also increased by 50%. Further experiments conducted on perifused hepatocytes showed that the putative adaptation at the level of the phosphoenolpyruvate-pyruvate cycle, which could be involved in the increased J(glucose) from lactate-pyruvate, was not involved in the increased J(glucose) from alanine after training. For alanine concentration higher than approximately 1 mM, an increased flux through alanine aminotransferase appeared responsible for the increased J(glucose). This could, in turn, depend on an increased supply of cytosolic 2-oxoglutarate because of the higher mitochondrial respiration observed in hepatocytes from trained rats and the activation of the malate-aspartate shuttle. At lower alanine concentration, the increase in J(glucose) appeared to be entirely due to the improved transport capacity.

Alanine↗

PubMed1999

Enteral nutrition in intensive care patients: a practical approach.

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 these patient's management. 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 decision-making 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.

Contraindications↗