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L Cynober

Publications and source records attributed to L Cynober.

At least 37 records · Page 2Linked to original sources

Cytokine-mediated inhibition of ketogenesis is unrelated to nitric oxide or protein synthesis.

Cytokines play an important role in the lipid disturbances commonly associated with sepsis. Ketogenesis is inhibited during sepsis, and tumor necrosis factor alpha (TNF alpha) and interleukin-6 (IL-6) have been suggested to mediate this impairment, irrespective of the ketogenic substrate (fatty acid or branched chain ketoacid). However, the underlying mechanism of cytokine action is still unknown. First we investigated the possible role of the induction of nitric oxide (NO) synthesis, using rat hepatocyte monolayers. Hepatocytes were incubated for 6 h, with either alpha -ketoisocaproate (KIC) (1 mM) or oleic acid (0.5 mM) in the presence or absence of TNF alpha (25 microg/L) and IL-6 (15 microg/L). In some experiments, cells were incubated with NO synthase (NOS) inhibitors. The ketone body (beta -hydroxybutyrate and acetoacetate) production and nitrite production were measured in the incubation medium. Our results indicated no involvement of nitric oxide in the inhibitory action of cytokines on ketogenesis. Secondly, we showed that cycloheximide (10(-4)M) did not counteract the cytokine-mediated ketogenesis decrease; hence, the effects of cytokines on ketogenesis are not protein synthesis-dependent. The cytokine-mediated inhibition of ketogenesis is therefore unrelated to either NO production or protein synthesis.

Animals↗

Amino acid metabolism during total parenteral nutrition in healthy volunteers: evaluation of a new amino acid solution.

The aim of this study was to determine the metabolism and the tolerance of a new amino acid (AA) solution administered under conditions mimicking cyclical parenteral nutrition (PN) in humans. Eight healthy volunteers received peripheral PN for 10 h providing 10.5 mg N x kg(-1) x h(-1) and 2.0 kcal x kg(-1) x h(-1) (glucose-to-lipids ratio: 70/30%). For adaptation, a non-protein energy intake was increased progressively for 90 min; thereafter, AA infusion was started and maintained at a constant rate for 10 h. Plasma and urine concentrations of all the AAs were measured before, during and after the PN. For each given AA, the relation between plasma variations at the steady-state and infusion rate, plasma clearance (Cl), renal clearance (Clr), re-absorption rate (Reab) and, retention rate (Reten) were determined. The nitrogen balance (DeltaN) was calculated during the PN period. The results are presented as means+/-sem. All plasma AA concentrations decreased during the starting period of non-protein energy intake. The plasma AA concentrations reached a steady-state within 3 h upon AA infusion, except for glycine and lysine (6 h). At the steady state, the plasma concentrations of the infused AAs were closely correlated to their infusion rate (y= -18.3+1.5x, r(2)=0.92). The plasma glutamine concentration was maintained during the PN, which indicates that the solution might stimulate the de novo synthesis of this AA. When the PN was stopped, plasma levels of the AAs decreased, most of them returning to their basal levels, or significantly below for lysine (P<0.05), alanine (P<0.05), proline (P<0.01) and glutamine (P<0.05). No volunteer showed any adverse effect during the infusion period. DeltaN was: 0.8+/-0.5 gN/10 h. Metabolic characteristics for essential AAs were: Cl<0.5 l min(-1), Clr <1.5 ml x min(-1) Reab >or= 99%, Reten >or=99% and for non-essential AAs: Cl <0.6 l x min(-1) except aspartate (2.8+/-0.3 l x min(-1)), Clr < 3 ml x min(-1) except glycine (6.8+/-0.7), aspartate (8.2+/-3.5) and histidine (8.8+/-1.3); Reab >or= 98% except glycine (95+/-1), aspartate (94+/-2) and histidine (94+/-1), Reten >or=97% except histidine (94+/-1), glycine (95+/-3). These results indicate that in healthy subjects, the amounts of AAs provided by the new solution were well balanced for an intravenous administration, and so were well utilized without excessive urinary excretion. The present study provides useful metabolic parameters for a further evaluation in disease.

Adult↗

Should a single centre for the assay of biochemical markers of nutritional status be mandatory in multicentric trials?

Clinical trials to identify patients at risk and to assess new therapeutic agents in the nutritional field are often single-site. The principal advantage of mounting a multicentric trial is that patient accrual is much quicker. Albumin, transthyretin, and C-reactive protein are frequently used biochemical markers of nutritional and inflammation status. However, the different techniques, reagents, and calibrators used to measure these markers introduce wide variations in values among laboratories. This study was carried out as part of a prospective multicentric study in chronic respiratory disease patients to evaluate variability and comparability of results among laboratories for these biochemical markers, and to determine whether centralization is necessary. Thirty enrolled laboratories provided their own range of reference values for those proteins a nd were then requested to process two control samples C1 and C2 blind. The results showed a broad dispersion of values for albumin and transthyretin. In 7% of laboratories, results of albumin for C2 (mean, all techniques: 39.1+/-3 g/l) were <35 g/l, the threshold value indicating a potential risk of malnutrition. When only laboratories using immunonephelemetry were considered, the results were satisfactory (CV<10% for all proteins). Given the possible incorrect classification of patients at risk, measurement should be made per site only if all participants use an immunonephelometric method. Otherwise, a centralizing assay of these biological markers should be considered.

Biomarkers↗

Specific and nonspecific immune responses to fasting and refeeding differ in healthy young adult and elderly persons.

BACKGROUND: Undernutrition is a main cause of immunodeficiency. Many confounding factors limit the interpretation of immune function in hospitalized elderly patients. OBJECTIVE: We compared the effects of short-term fasting and refeeding on lymphocyte subset distribution and neutrophil function in healthy subjects. DESIGN: Seven young adult (x +/- SE age: 24 +/- 2 y) and 8 elderly (71 +/- 3 y) subjects were fed standardized diets (1.6 x predicted resting energy expenditure; 16% protein) for 7 d. They then fasted for 36 h and were refed for 4 h (42 kJ/kg). Lymphocyte subsets were quantified by using fluorochrome-conjugated monoclonal antibodies. Neutrophil chemotactic migration was evaluated by using a 2-compartment chamber. Neutrophil reactive oxygen species production was measured by using a luminol-amplified chemiluminescence assay and oxidation of 2'7'-dichlorofluorescein diacetate. RESULTS: Baseline total and cytotoxic T lymphocyte subpopulations were lower in elderly than in adult subjects (P < 0.01). Nutritional state had a significant effect (P < 0.05) on total, helper, and cytotoxic T and B lymphocyte counts in all subjects, and the response of lymphocyte subpopulations to nutritional fluctuations was significantly affected by age. The chemotactic index was lowered by fasting in both groups (P < 0.05 compared with basal values). After refeeding, neutrophil migration was restored in adult but not elderly subjects. The superoxide anion production rate increased with fasting and reverted to prefasting values with refeeding in both groups (P < 0.05). Fasting induced a significant decrease in hydrogen peroxide production in stimulated neutrophils that was reversed by refeeding in adult but not elderly subjects. CONCLUSION: The lack of response of lymphocyte subpopulation counts and neutrophil function to nutritional changes may help to explain the proneness of elderly persons to infection.

Adult↗

A pancreatic extract-enriched diet improves the nutritional status of aged rats.

Correction of the malnourished state, particularly common and severe in elderly people, is often unsuccessful. To improve the efficiency of realimentation, we evaluated the nutritional effect of a pancreatic extract (PE)-enriched diet in malnourished aged rats. Sprague-Dawley male rats were randomly assigned to 6 groups as follows: 1 group of control rats had free access to the diet for 12 wk (C group) and 5 groups were 50% food restricted for the same period. One food-restricted group was then killed (R group) and the 4 remaining groups were refed for 1 wk using a standard diet enriched either with two different doses of a pancreatic extract (2.4 or 4.8 g/d in PE1 and PE2 groups, respectively) or with an isonitrogenous casein hydrolysate (CH1 and CH2 groups, respectively). Profound alterations induced by food restriction (FR) were moderately corrected by refeeding, except nitrogen balance, which was reestablished in rats refed all diets (P: < 0.01 vs. R). Supplementation of the food ration with a pancreatic extract clearly improved recovery. Indeed, body weight gain, both jejunal and ileal trophicity [jejunum: total height, PE2: 849 +/- 45 microm vs. CH2: 768 +/- 17 microm (P: < 0.05); protein content, PE2: 69.9 +/- 5.7 mg vs. CH2: 56.4 +/- 4.8 mg (P: < 0.01)] and nonspecific immune response in terms of H2O2 production by polymorphonuclear neutrophils and tumor necrosis factor alpha (TNF-alpha) by macrophages (PE2, 20.7 +/- 4.7 vs. CH2, 8.7 +/- 2.3, P: < 0.05) were improved in rats fed PE2. A pancreatic extract could improve the efficiency of realimentation in malnourished aged rats.

Aging↗

Involvement of glutamine, arginine, and polyamines in the action of ornithine alpha-ketoglutarate on macrophage functions in stressed rats.

The ability of ornithine alpha-ketoglutarate (OKG) to enhance macrophage cytotoxicity in stress situations has been described, but the mechanisms involved remain unclear. It is known that OKG administration generates glutamine (GLN), arginine (ARG), and polyamines. This study will (1) evaluate the effect of OKG on tumor necrosis factor alpha (TNF-alpha) secretion and nitric oxide (NO*) production in macrophages from glucocorticoid (DEX)-treated rats, and determine whether these effects can be reproduced by GLN or ARG supplementations, and (2) use in vivo metabolic inhibitors methionine sulfoximine (inhibitor of GLN synthetase), S-methylthiourea (inhibitor of inducible nitric oxide synthase), and difluoromethylornithine (inhibitor of ornithine decarboxylase) to assess the roles of GLN, ARG, and polyamines in OKG action. Controls received a mixture of nonessential amino acids (NEAA). GLN, ARG, and OKG all restored TNF-alpha secretion by macrophages of glucocorticoid-treated rats. The same results were obtained with GLN and ARG supplementation. However, the use of inhibitors clearly showed that OKG does not modulate TNF-alpha secretion by GLN, ARG, or polyamine pathways. We also observed that OKG enhanced NO* release by stimulated macrophages (DEX-OKG, 1.77 +/- 0.64 vs. DEX-NEAA, 0.29 +/- 0.29 nmol/ 10(6) cells, P < 0.05). Using inhibitors, it appears that this action of OKG is probably mediated via polyamine synthesis and GLN. However, an oral administration of an equimolar amount of GLN failed to reproduce the OKG-mediated effect, possibly because OKG generates more GLN in the systemic circulation than GLN itself when these substances are given orally. Our results underline the complexity of the mechanism of action of OKG, which can differ according to the functions of even a single cell type.

Animals↗

Prevention of proteolysis in cold-stored rat liver by addition of amino acids to the preservation solution.

BACKGROUND: One process identified as detrimental in liver preservation is proteolysis. METHODS: We tested the effects of adding antiproteolytic amino acids (L-alanine, L-glutamine, L-histidine, L-leucine, L-methionine, L-phenylalanine, L-proline, L-tryptophan) to the preservation medium, in a model of reperfusion of 24 h cold-stored rat livers. RESULTS: During the preservation period, antiproteolytic amino acids inhibited the proteolysis observed in stored livers as shown by branched-chain amino acid fluxes, which switched from release to uptake. During reperfusion, cold storage of lives without the addition of antiproteolytic amino acids resulted in a decrease in the total amino acid and branched-chain amino acid uptake and a lower perfusion flow rate. The addition of antiproteolytic amino acids during liver storage resulted in the maintenance of total amino acid and branched-chain amino acid uptake and a significant improvement in the perfusion flow rate during reperfusion. CONCLUSIONS: The presence of antiproteolytic amino acids in the preservation medium might be of interest in improving hepatic graft viability in transplantation.

Amino Acids↗

Postabsorptive plasma citrulline concentration is a marker of absorptive enterocyte mass and intestinal failure in humans.

BACKGROUND & AIMS: No blood marker assessing the functional absorptive bowel length has been identified. Plasma citrulline, a nonprotein amino acid produced by intestinal mucosa, is one candidate. We tested this hypothesis in adult patients with the short-bowel syndrome, whose condition can lead to intestinal failure. METHODS: In 57 patients, after a minimal follow-up of 2 years subsequent to final digestive circuit modification, postabsorptive citrulline concentration was measured and parenteral nutrition dependence was used to define permanent (n = 37) and transient (n = 20) intestinal failure. Absorptive function, studied over a 3-day period, was evaluated by net digestive absorption for protein and fat (n = 51). Relations between quantitative values were assessed by linear regression analysis and cutoff citrulline threshold, for a diagnosis of intestinal failure by linear discriminant analysis. Cox model was used to compare citrulline threshold and anatomic variables of the short bowel as indicators of transient as opposed to permanent intestinal failure. RESULTS: In patients with short-bowel syndrome, citrulline levels were lower than in controls (n = 51): 20 +/- 13 vs. 40 +/- 10 micromol/L (mean +/- SD), respectively (P < 0.001). After multivariate analysis, citrullinemia was correlated to small bowel length (P < 0.0001, r = 0.86) and to net digestive absorption of fat, but to neither body mass index nor creatinine clearance. A 20-micromol/L threshold citrullinemia, (1) classified short bowel patients with permanent intestinal failure with high sensitivity (92%), specificity (90%), positive predictive value (95%), and negative value (86%); and (2) was a more reliable indicator (odds ratio, 20.0; 95% confidence interval, 1.9-206.1) than anatomic variables (odds ratio, 2.9; 95% confidence interval, 0. 5-15.8) to separate transient as opposed to permanent intestinal failure. CONCLUSIONS: In patients with short-bowel syndrome, postabsorptive plasma citrulline concentration is a marker of functional absorptive bowel length and, past the 2-year adaptive period, a powerful independent indicator allowing distinction of transient from permanent intestinal failure.

Absorption↗

Aging: a barrier to renutrition? Nutritional and immunologic evidence in rats.

BACKGROUND: Previous reports suggest that correcting the malnourished state is more difficult in elderly people than in younger ones and that protein requirements may be higher in elderly than in younger adults. OBJECTIVE: The aim of this study was to establish whether malnourished old rats respond to protein-supplemented nutritional repletion as do young adult rats. DESIGN: Adult (3 mo old) and old (22 mo old) rats were submitted to dietary restriction programs that induced similar metabolic and nutritional alterations. Malnourished adult and old rats were then killed (R groups) or refed for 1 wk with a high-protein diet (HPD; 23% protein) or a very-high-protein diet (VHPD; 27% protein). Control groups at both ages were fed ad libitum throughout the experiment. Effects of food repletion were evaluated in terms of protein metabolism, intestinal histomorphometry, and nonspecific immune status. RESULTS: In adult rats, HPD sufficed to increase body weight and restore basal values of liver weight and protein content (P: < 0.01 compared with the R adult group), nitrogen balance (P: < 0.01 compared with the R adult group), and hydrogen peroxide production by polymorphonuclear neutrophils and monocytes (P: < 0.01 compared with the R group); VHPD had no supplementary effect except on nitrogen balance. In old rats, HPD was less effective and greater benefit was observed with VHPD in terms of body weight gain (10%; P: < 0.01 compared with the old group fed HPD), albuminemia, muscle weight and protein content, plasma arginine concentration, and hydrogen peroxide production by stimulated polymorphonuclear neutrophils and monocytes compared with the old R group (P: < 0.01). CONCLUSION: Aging is a significant variable affecting the response to nutritional support.

Aging↗

Bacterial dissemination and metabolic changes in rats induced by endotoxemia following intestinal E. coli overgrowth are reduced by ornithine alpha-ketoglutarate administration.

The efficacy of ornithine alpha-ketoglutarate (OKG) in preventing bacterial translocation and dissemination, metabolic disorders and changes in mucosal enzyme activities was assessed in a model of bacterial translocation in rats. Antibiotic decontamination was performed 4 d before intragastric inoculation with an Escherichia coli strain (10(10) bacteria/kg body). Two days later, the rats were given either a lipopolysaccharide (LPS) 0127:B8 or a saline injection and were deprived of food for 24 h. Enteral nutrition, [Osmolite, 880 kJ/(kg. d)] supplemented with either OKG (LPS + OKG) or glycine (Saline + Gly or LPS + Gly), was then given for 2 d. Urinary total nitrogen losses and 3-methylhistidine excretion were determined daily. On killing at d 3, bacterial translocation to the mesenteric lymph nodes (MLN) and dissemination to the spleen and liver were evaluated, jejunal mucosa enzyme activities were assayed and tissue free amino acids in muscles were measured. Endotoxin induced translocation from the gut lumen to the MLN in all groups, whereas dissemination occurred only in LPS-treated rats. OKG significantly reduced dissemination of the bacteria in the spleen. 3-Methylhistidine excretion was greater in the LPS + Gly group (+25%, P: < 0.05) than in either the LPS + OKG or Saline + Gly group. The group fed the OKG-enriched diet had higher muscular glutamine, ornithine and arginine concentrations than did the Gly-supplemented groups (P: < 0.05). Intestinal sucrase and aminopeptidase activities were higher in the LPS + OKG group than in the LPS + Gly group (-30%, P: < 0.05). OKG supplementation limits bacterial dissemination and metabolic changes after injury in rats and thus may be useful in the prevention of gut-derived sepsis in critically ill patients.

Animals↗

Ornithine alpha-ketoglutarate improves wound healing in severe burn patients: a prospective randomized double-blind trial versus isonitrogenous controls.

OBJECTIVE: To compare the effectiveness on wound healing time in severe burn patients of ornithine alpha-ketoglutarate supplementation of enteral feeding vs. an isonitrogenous control. Previous clinical and experimental studies suggest a beneficial effect of enterally administered ornithine alpha-ketoglutarate supplementation on protein metabolism in burn patients, but few data deal with clinical outcome. DESIGN: Prospective double-blind randomized trial. SETTING: Burn treatment center of an army hospital. PATIENTS: Forty-seven severe burn patients with total burned body surface areas of 25% to 95% and presence of full thickness burn who were prescribed early exclusive enteral nutrition. Either ornithine alpha-ketoglutarate or isonitrogenous control (soy protein mixture, Protil-1) were administered twice a day as a bolus (2 x 10 g) at 9 am and 9 pm for 3 wks. The patients were evaluated for wound healing time (primary end point), antibiotic use, tolerance, duration of enteral nutrition, and nutritional status. INTERVENTIONS: Serial blood samples were collected in each patient for determination of serum transthyretin and plasma phenylalanine, and urine sampling was performed for determination of 3-methylhistidine excretion at day 4 and day 21 after burn injury. MEASUREMENTS AND MAIN RESULTS: Wound healing times in patients receiving ornithine alpha-ketoglutarate or Protil-1 were 60 +/- 7 and 90 +/- 12 days, respectively (p < .05) for similar grafted surfaces. Based on increased serum transthyretin concentrations, both groups showed an improvement of nutritional status at day 21 after burn. Taking a cut-off value of 110 unit burn standard for severity of injury, plasma phenylalanine concentrations, and urinary 3-methylhistidine/creatinine ratio were significantly reduced (p < .05) in the less severe burn patients (<110 unit burn standard) supplemented with ornithine alpha-ketoglutarate. CONCLUSIONS: Ornithine alpha-ketoglutarate supplementation of enteral feeding significantly shortens wound healing time in severe burn patients. In addition, ornithine alpha-ketoglutarate administration was safe and well tolerated and decreased protein hypercatabolism in the less severe burn patients.

Adult↗

Total parenteral nutrition enriched with arginine and glutamate generates glutamine and limits protein catabolism in surgical patients hospitalized in intensive care units.

OBJECTIVES: To study the effect of a parenteral nutrition solution enriched with potential precursors of glutamine, i.e., arginine and glutamate, on plasma glutamine concentrations and protein metabolism. DESIGN: Prospective, randomized, single-blind, comparative study. SETTING: Two intensive care units in two different hospitals. PATIENTS: Fifteen surgical patients. INTERVENTIONS: Patients were randomized to receive total parenteral nutrition for 5 days with the enriched glutamine precursor solution (GlnP+ group) or a conventional solution (control group), both total parenteral nutrition providing 0.25 gN/kg per day and 35 kcal/kg per day (glucose/lipids, 70%:30%). MEASUREMENTS AND MAIN RESULTS: Plasma amino acid concentrations before (T0) and after 3 hrs (T3) of perfusion, nitrogen balance (daily and cumulated), and urinary excretion of 3-methylhistidine were measured daily from day 1 to day 5. The two groups were identical for age, weight, severity score, and nitrogen and energy intakes. After a 3-hr perfusion, plasma concentrations of arginine, ornithine, and glutamine increased, and the differences (T3 - T0) were significantly higher in the GlnP+ group: arginine, 107.6+/-7.0 vs. 51.9+/-3.3 (mean over 5 days; p < .001); ornithine, 78.9+/-7.1 vs. 43.6+/-3.1 (p < .001); and glutamine, 32.4+/-8.6 vs. 6.7+/-5.0 micromol/L (p < .05), respectively. A positive correlation was found between arginine and glutamine plasma increases only in the GlnP+ group: r = .45; p < .01 (Spearman's rank-correlation test). Daily and cumulated nitrogen balances were not significantly different between the two groups but were positive (difference from 0) only in the GlnP+ group. The urinary 3-methylhistidine/creatinine ratio decreased significantly from day 1 to day 5 only in the GlnP+ group: 24.5+/-2.7 vs. 18.8+/-2.7 micromol/mmol (p < .05). CONCLUSIONS: Total parenteral nutrition enriched with arginine and glutamate promotes a better nitrogen balance, limits protein myofibrillar catabolism, and generates glutamine, with arginine (not glutamate) probably being the main contributor to the glutamine-generating effect of the solution through the formation of ornithine.

Adolescent↗

Evaluation of a newly available biochemical analyzer: the Olympus AU 600.

The performance of the Olympus AU 600, a newly available open multiparametric analyzer, available for routine biochemical analysis of biological samples, was evaluated. The analytical and technical performance of the apparatus and the quality of the Olympus reagents were both examined in a single site study. Electrolyte concentrations were determined with patented ion-selective electrodes; substrate concentrations and enzyme activities were determined by spectrophotometric measurement after coloured reaction or UV detection-based-reactions. The protocol of the evaluation and the acceptability criteria were those recommended by the French Society for Clinical Biology. For the parameters studied, the upper limits of linearity were equal to or higher than those claimed by the manufacturer. The CV values for within-run and between-run precision were lower than the target values with few exceptions. The comparison study gave satisfactory results for most of the parameters. Only expected interferences occurred. In summary, the results obtained for the 25 parameters studied and the characteristics of the apparatus were satisfactory. The analyzer is rapid (800 to 1200 tests per hour) and easy to use. In addition, the analyzer complies with good analytical practice and its flexibility enables users to plan work according to local laboratory constraints.

Autoanalysis↗

Branched-chain keto-acids and pyruvate in blood: measurement by HPLC with fluorimetric detection and changes in older subjects.

BACKGROUND: Measurement of keto-acids is important in various clinical situations. The aim of the present work was to develop a rapid HPLC method for the determination of keto-acids in human serum and to assess the concentrations of these acids in young adults and institutionalized elderly adults. This method was applied to the determination of blood keto-acid concentrations of young adults and institutionalized elderly people, divided into age groups METHODS: Four keto-acids (alpha-ketoisocaproate, alpha-ketoisovalerate, alpha-keto-beta-methylvalerate, and pyruvate) were derivatized with o-phenylenediamine to give fluorescent derivatives. After the sample preparation step (75 min to prepare 20 samples), the derivatives were separated chromatographically on a reversed-phase column using a binary gradient. RESULTS: The fluorometric detection of the four keto-acids was rapid, <12 min. The method is repeatable and reproducible: the CVs were <6% and <11%, respectively, for each of the keto-acids. We found no significant difference between males and females. Concentrations of the branched-chain keto-acids decreased after age 60 years, especially alpha-ketoisocaproate, which decreased approximately 40%. CONCLUSIONS: The proposed method allows rapid and reliable measurement of keto-acids. The data demonstrate that changes in branched-chain keto-acids concentrations in serum occur with age.

Adult↗

[Role of amino acids in the host-tumor relationship. Physiopathological and therapeutic aspects].

Cancer frequently leads to malnutrition resulting from reduced food intake and hypermetabolism, both induced by cytokine-like factors. There is thus a competition between the host and the tumor for utilization of nutrients such as certain amino acids. These data lead to two possible therapeutic strategies. The first consists in depleting the organism of certain amino acids such as methionine and glutamine. The result is a reduction in tumor growth, but also a deleterious effect on the host. The second is to provide diets enriched in amino acids stimulating the host immune system (i.e. glutamine, arginine, ornithine alpha-ketoglutarate). This approach has given interesting results in experimental models as well as in cancer patients.

Amino Acids↗

A Na(+)-dependent system A and ASC-independent amino acid transport system stimulated by glucagon in rat hepatocytes.

The effects of glucagon on amino acid transport in rat hepatocytes are not fully understood. We examined the effect of this hormone on alanine, serine and cysteine preferring system (system ASC)-mediated amino acid transport in rat hepatocyte monolayers using 2-aminoisobutyric acid (AIB) and l -cysteine. Glucagon induced a time and protein synthesis-dependent stimulation of Na(+)-dependent alanine preferring system (system A)-independent AIB transport. The glucagon-induced increase in transport activity was not modified by substrate starvation and not related to changes in the intracellular pool of amino acids. Glucagon did not modify system ASC activity measured by l -cysteine. Therefore the transport activity of AIB independent of system A stimulated by glucagon cannot be attributed to system ASC. This suggests a Na(+)-dependent transport system in rat hepatocytes not identified until now.

Amino Acids↗

Is the L-arginine-nitric oxide pathway involved in endotoxemia-induced muscular hypercatabolism in rats?

We investigated the role of the nitric oxide (NO) synthase (NOS) pathway in muscular metabolism during endotoxemia in four groups of male Wistar rats. Two groups were injected with the lipopolysaccharide (LPS) of Escherichia coli (3 mg/kg), with one group treated using N(G)-nitro-L-arginine methylester ([L-NAME] 85 mg/kg/d) and the other not. The two control groups included one treated with L-NAME and the other not. After 24 hours of fasting, the rats were fed by controlled enteral nutrition and killed on day 3. The results showed that (1) NOS inhibition was detrimental during endotoxemia, increasing lethality from 20% to 80.5%, and (2) NOS inhibition did not modify the hypercatabolic state consecutive to endotoxemia, particularly at the muscular level (nitrogen balance, total-body and muscular weight loss, and muscular protein and glutamine concentrations). However, myofibrillar catabolism was delayed in the LPS-NAME group. In conclusion, NO production is of major importance for survival after an endotoxemic challenge, but contributes weakly to the metabolic response of muscle to injury.

Animals↗