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Biomedical subjects

L Cynober

Publications and source records attributed to L Cynober.

At least 55 records · Page 3Linked to original sources
PubMed1999

Abnormalities in branched-chain amino acid metabolism in cirrhosis: influence of hormonal and nutritional factors and directions for future research.

Plasma branched-chain amino acid (BCAA) levels are decreased in patients with liver cirrhosis, owing to an increase in BCAA tissue uptake and/or catabolism and a decrease in BCAA production from proteins. Non-specific factors such as malnutrition worsen this picture. Studies of BCAA fluxes and protein turnover in cirrhotic patients have given conflicting results due to patient heterogeneity, differences in method and bias in the expression of results. In well compensated cirrhosis, muscle wasting is moderate and probably due more to decreased protein synthesis than to increased protein catabolism. Hyperinsulinemia has been suggested as the main cause of decreased BCAA levels, by increasing BCAA uptake in muscle and additionally in adipose tissue. However, as depletion of fat stores is frequent in cirrhosis, this effect is certainly quantitatively weak. Also, there is no correlation between state of hyperinsulinemia and decrease in BCAA levels. An effect of cytokines (IL1 and TNF) on muscle BCAA catabolism is a possibility. Until recently, the contribution of the liver to abnormal BCAA metabolism has been underestimated. In cirrhotic liver an increase in liver transamination of branched-chain keto acids (BCKAs) has been suggested and may result from inhibition of liver BCKA dehydrogenase. A modification of protein turnover in cirrhotic liver must be also considered. Lastly, the contribution of non-hepatocyte liver cells, which are activated in cirrhosis, remains to be assessed.

Amino Acids, Branched-Chain↗
PubMed1999

Ornithine alpha-ketoglutarate counteracts the decrease of liver cytochrome P-450 content in burned rats.

The effect of ornithine alpha-ketoglutarate (OKG) on cytochrome P-450 enzyme activities was studied in a well-defined model of injury (burn followed by fasting then subsequent hypocaloric diet) administered to young rats for 3 d. Hepatic microsomes were prepared by ultracentrifugation and levels of cytochromes P-450 were determined spectrophotometrically. The activities of ethoxy-resorufin-O-deethylase (EROD), benzyloxy-resorufin-O-dealkylase (BROD), and erythromycin demethylase were measured as markers of P-450 1A, 2A, and 3A isotypes respectively. The level of total hepatic microsomal proteins (8 mg/mL) remained constant. The level of cytochrome P-450 (1.14+/-0.08 nmol/mg microsomal proteins) was decreased by a hypocaloric diet (23%, P = 0.003) and burn further enhanced this phenomenon (15%, P = 0.03). Both healthy and burned rats receiving OKG showed the same level of cytochrome P-450 as the rats fed ad libitum. OKG supplementation counteracted the enhancement (40%) of EROD activity induced by hypocaloric diet but did not influence BROD and erythromycin demethylase activities. OKG sustained cytochrome P-450 levels in rats fed a hypocaloric diet, even after burning. These findings indicate that OKG may favor drug metabolism in this injured population.

Animals↗
PubMed1999

Modulation of immune response with ornithine A-ketoglutarate in burn injury: an arginine or glutamine dependency?

Enterally administered ornithine alpha-ketoglutarate (OKG) is an efficient complement of nutritional support in trauma situations, especially after burn injury. A typical feature observed in this intense catabolic state is insufficient production of glutamine (Gln) and arginine (Arg), two amino acids (AAs) involved in the immune response. As OKG in vivo metabolism generates these two AAs, we investigated, in burned rats, the action of OKG with regard to modulation of immunity. Male Wistar rats were randomly allocated to four groups. On day 0, 12 rats were burned with boiling water (20% body surface area). After a 24-h fast, they were enterally refed for 48 h using Osmolite, as a low-calorie low-nitrogen regimen, supplemented with either 5 g OKG x kg(-1) x d(-1) (n = 6) or an equivalent amount of nitrogen in the form of glycine (n = 6). Non-burned pair-fed controls treated with glycine (n = 6) and healthy rats fed ad libitum (n = 6) were also studied. Nitrogen balance was assessed from daily measurement of total nitrogen excretion. On day 3, thymus, Anterior tibialis muscle and proximal jejunum weights were recorded. Muscle and intestinal AA concentrations were also quantified. OKG counteracted (P<0.01) the thymic involution that occurs with burn injury, and increased the concentrations of Gln and Arg in both the muscle (P<0.01 and P<0.05, respectively) and the jejunum (P<0.01 for Gln). When all groups were taken together, a positive correlation was found between thymus weight, and Gln and Arg muscle concentrations (r = 0.71, P<0.001 and r = 0.58, P<0.01, respectively). Furthermore, as expected, OKG improved nitrogen balance. As it is known that total number of thymocytes parallels thymic weight, and as Gln and Arg are essential nutrients for activated immune cells, our results suggest that Gln and Arg derived from OKG are responsible for the immunomodulating properties of this molecule in burn injury.

Animals↗
PubMed1999

Can a glutamate-enriched diet counteract glutamine depletion in endotoxemic rats?

The study evaluated whether a glutamate-enriched diet would restore glutamine tissue pools and maintain tissue trophicity in endotoxemic rats. For this purpose, young male Sprague-Dawley rats received an intraperitoneal injection of lipopolysaccharide (LPS) from Escherichia coli at 3 mg/kg body weight. After 24 hours of food deprivation, the rats were enterally refed for 48 hours using Osmolite enriched with glutamate at 4 g/kg/d (LPS-Glu group, n = 7) or glycine isonitrogenous to glutamate (LPS-Gly group, n = 7). A control group (healthy group, n = 7) had free access to a standard rodent diet. Tissue weights and protein contents were significantly lower in both LPS-treated groups than in the healthy group. No plasma or tissue accumulation of glutamate was observed except in the liver. Glutamine concentrations were increased in the jejunum, liver, and plasma in the LPS-Glu group versus the other two groups (P < 0.05). Conversely, they were depleted in muscles of the endotoxemic groups versus the healthy group (P < 0.05). Villus height was significantly greater in the LPS-Glu group than in the LPS-Gly group in the jejunum (P < 0.05), but not in the ileum. In conclusion, a glutamate-enriched diet administered enterally to endotoxemic rats can counteract glutamine depletion in the splanchnic area but not in muscles. In addition, glutamate displayed a trophic effect restricted to the jejunum.

Journal Article↗
PubMed1999

Severe dietary restriction initiated in aged rats: evidence for poor adaptation in terms of protein metabolism and intestinal functions.

BACKGROUND: Protein energy malnutrition is a common finding in elderly people, increasing morbidity and mortality in aged inpatients. Investigations need to be developed to counteract malnutrition-induced alterations early and to avoid potential irreversible lesions. The aim of this experimental study was to evaluate time-response to severe dietary restriction (DR) initiated in aged rats in terms of protein metabolism and digestive trophicity. MATERIALS AND METHODS: After the acclimatization period, 22-month-old male rats were randomized into six groups: three control groups, fed ad libitum for 3, 6 or 12 weeks with a standard diet and three corresponding dietary-restricted groups fed for the same periods with only 50% of the spontaneous intake. Intestinal mucosa, liver and skeletal muscles (soleus, extensor digitorum longus and tibialis anterior muscle) were removed when the rats were killed. RESULTS: DR induced dramatic body weight loss (up to 50% of initial body weight after 12 weeks DR). Protein metabolism was affected in terms of nitrogen balance (P < 0.01) and protein content, in particular at the splanchnic level. Morphometrically, the intestine structure was altered after 12 weeks of DR (P < 0.01), and this atrophy was correlated with malabsorption of mannitol (P < 0. 01). Ileal hydrolase activities were decreased throughout the 12 weeks of DR. CONCLUSIONS: Aged rats clearly exhibit a defect of adaptation to long-term DR initiated at an advanced age. Severe DR leads to malnutrition, which becomes of major importance after 12 weeks, in particular at the intestine level. Hence, application of these experimental results to elderly, malnourished people may contribute to a better knowledge of denutrition-induced disorders.

Aging↗
PubMed1999

Oral administration of a glutamine-enriched diet before or after endotoxin challenge in aged rats has limited effects.

Numerous studies indicate beneficial effects of glutamine (Gln) in many models of catabolic adult rats. No data were available for aged rats. The effects of oral L-Gln-enriched diet were tested in endotoxemic 24-mo old rats. First, rats received for 7 d (from d0 to d7) an oral diet supplemented with either L-Gln [1g/(kg. d)] or casein (Cas: isonitrogenous supply) prior to lipopolysaccharide (LPS) challenge. The rats were then killed after 24 h food deprivation (from d7 to d8). Endotoxemia induced a catabolic response as shown by muscle glutamine depletion, hyperphenylalaninemia, small bowel atrophy and impaired functionality and bacterial translocation. The Gln-enriched diet did not prevent muscle Gln depletion but significantly (P </= 0.05) enhanced plantaris protein content by 18% compared to the Cas-LPS rats and reduced the plasma phenylalanine-to-tyrosine ratio (1.32 +/- 0.05 vs. 1.54 +/- 0.10, respectively, P </= 0.01). Gut translocation and histomorphology were unaffected by diet. However, Gln pretreatment reduced the fall in sucrase and glucoamylase activities in the ileum, respectively, by 55 and 63% vs. Cas supplementation (P </= 0.05). In a second study, after endotoxin challenge, healthy 24-mo-old rats were then food-deprived for 2 d (from d0 to d2), received a nonpurified diet for 4 d (from d2 to d6), and then Cas or L-Gln-supplemented diet for 7 d (from d6 to d13). No beneficial effects of Gln supplementation were observed except an increase of 50 and 56% in sucrase and glucoamylase activities in the ileum of Gln-treated rats, (P </= 0.01 vs. healthy rats). In conclusion, the effects of L-Gln supplementation in aged endotoxemic rats were limited.

Aging↗
PubMed1999

Bacterial dissemination, rather than translocation, mediates hypermetabolic response in endotoxemic rats.

OBJECTIVE: To study the pathogenesis of the host response during bacterial translocation, a rat model was designed for prolonged follow-up after injury. DESIGN: A prospective, controlled animal study. SETTING: Animal laboratory. SUBJECTS: Young male Wistar rats. INTERVENTIONS: Antibiotic decontamination of rats was performed 4 days before intragastric inoculation with a selected Escherichia coli strain (10(10) bacteria/kg of body weight). Two days later, the rats received a lipopolysaccharide injection or not (control group) and were observed for 3 days. They were then killed. A reference group (pair-fed healthy animals) was studied in parallel. MEASUREMENTS AND MAIN RESULTS: During observations, urinary total nitrogen loss and 3-methylhistidine excretion were determined daily. When the rats were killed, mesenteric lymph nodes (MLNs), spleen, and liver were aseptically removed and cultured. Colonies identified as translocated E. coli were counted in each organ. Intracellular amino acid free pools were measured in extensor digitorum longus and anterior tibialis. Endotoxin induces bacterial translocation of bacteria from gut lumen to MLNs (100% vs. 59% in the lipopolysaccharide-untreated control group; p < .05) and dissemination to spleen and liver (65% and 45% of positive cultures after endotoxemia, respectively, vs. 6% and 12% in the control groups). No translocation occurred in the reference group. Evidence for the hypermetabolic response was seen in lipopolysaccharide-treated and infected rats, but protein catabolism was more closely related to the occurrence of bacterial dissemination to spleen and liver than to translocation alone (e.g., the cumulative 3-methylhistidine excretion during the observation period was 4.07+/-0.18 micromol in uninfected rats, 4.48+/-0.29 in rats with positive MLN cultures alone and 6.17+/-0.30 in MLN, spleen, or liver infected rats; 1 vs. 2, NS; 3 vs. 1, and 3 vs. 2, p < .05). CONCLUSIONS: Gut barrier failure is associated with a deep excessive catabolic response in the host. The mechanism by which the metabolic state affects the resistance to infection apparently involves amino acid metabolism.

Animals↗
PubMed1999

Kinetic impairment of nitrogen and muscle glutamine metabolisms in old glucocorticoid-treated rats.

Aged rats are more sensitive to injury, possibly through an impairment of nitrogen and glutamine (Gln) metabolisms mediated by glucocorticoids. We studied the metabolic kinetic response of adult and old rats during glucocorticoid treatment. The male Sprague-Dawley rats were 24 or 3 mo old. Both adult and old rats were divided into 7 groups. Groups labeled G3, G5, and G7 received, by intraperitoneal injection, 1.50 mg/kg of dexamethasone (Dex) for 3, 5, and 7 days, respectively. Groups labeled G3PF, G5PF, and G7PF were pair fed to the G3, G5, or G7 groups and were injected with an isovolumic solution of NaCl. One control group comprised healthy rats fed ad libitum. The response to aggression induced specifically by Dex (i.e., allowing for variations in pair-fed controls) appeared later in the aged rats (decrease in nitrogen balance from day 1 in adults but only from day 4 in old rats). The adult rats rapidly adapted to Dex treatment, whereas the catabolic state worsened until the end of treatment in the old rats. Gln homeostasis was not maintained in the aged rats; despite an early increase in muscular Gln synthetase activity, the Gln pool was depleted. These results suggest a kinetic impairment of both nitrogen and muscle Gln metabolisms in response to Dex with aging.

Aging↗
PubMed1998

Free amino acid concentrations in milk: effects of microwave versus conventional heating.

Microwave effects on free amino acid concentrations in milk versus a water bath heating were investigated in view of their importance for infant growth. Concentrations of few amino acids, such as aspartate, serine or lysine, are unchanged whatever the way and the temperature of heating. In contrast, tryptophan concentrations decreased similarly whatever the way of heating (110 +/- 3 mumol/l before heating vs 84 +/- 4 mumol/l after 30 degrees C microwave heating, p < 0.05). On the contrary, concentrations of glutamate and glycine increased more after water bath heating at 90 degrees C (325 +/- 4 and 101 +/- 1 mumol/1, respectively) than after microwave heating (312 +/- 4 and 95 +/- 1 mumol/l, respectively, p < 0.05) suggesting milk proteolysis. Moreover, the accumulation of ammonia observed at 90 degrees C with the water bath together with increase Glu levels might reflect a degradation of glutamine. An ornithine enrichment, more evident with microwave heating, was shown and could be of interest as it is a polyamine precursor. Also, considering few variations of free amino acid concentrations and the time saved, microwave heating appears to be an appropriate method to heat milk.

Amino Acids↗
PubMed1998

Enteral ornithine alpha-ketoglutarate enhances intestinal adaptation to massive resection in rats.

Ornithine alpha-ketoglutarate (OKG) has been advocated in the treatment of critically ill patients for its anabolic effect on protein metabolism. Since OKG is a precursor of glutamine, arginine, and polyamines, key substrates of intestinal metabolism and function, we investigated the influence of OKG on intestinal adaptation and trophicity and on glutamine status after small bowel resection. After massive (80%) small bowel resection, rats were enterally fed for 7 days with a standard diet supplemented with either OKG (2 g/kg/d) or an isonitrogenous amount of glycine. OKG induced an adaptative hyperplasia of the villi, demonstrated in the jejunum by an increase in the villus height to crypt depth ratio (OKG v control, 4.3+/-0.4 v 3.3+/-0.5, P < .01) along with an increase (P < .05) in ornithine decarboxylase (ODC) activity (+80%) and ornithine content (+102%). Plasma glutamine (+25%) and muscle glutamine (anterior tibialis [AT], +43%; extensor digitorum longus [EDL], +54%) and protein (AT, +32%) were significantly higher (P < .05) after OKG administration, supporting its role in the restoration of glutamine pools. In summary, enterally administered OKG, which enhances intestinal adaptation after massive resection and improves muscle glutamine and protein content, could contribute significantly to nutritional management after small bowel resection.

Adaptation, Physiological↗
PubMed1998

A pancreatic extract-enriched diet corrects ileal mucosa atrophy in endotoxemic aged rats.

An altered adaptive response of the pancreas and small intestine to nutritional stress has an adverse impact upon nutritional status in elderly humans or senescent rats. We evaluated the effects of a pancreatic extract nutritional supplement on intestinal mucosa adaptation in LPS-treated aged rats. Endotoxemic rats were starved for 48 hr and then refed ad libitum for four days with a standard diet. Afterwards they received, over one week, the standard diet enriched with either pancreatic extract (PE) (2.4 g/day) or casein (isonitrogenous to PE supplement). Healthy aged rats fed ad libitum with a standard diet were studied in parallel. Whereas no changes occurred in the jejunal segment, an adaptive villus hyperplasia was observed in the proximal ileum of rats receiving PE without an increase in the brush border hydrolase activities. Our results indicate that oral PE supplementation exerts a trophic effect on the ileal mucosa of aged rats in response to nutritional stress.

Aging↗
PubMed1998

Pharmacokinetic assessment of an oligopeptide-based enteral formula in abdominal surgery patients.

The specific effect of the molecular form of the nitrogen supply (oligopeptides and whole proteins) on amino acid kinetics during enteral feeding after surgery has not been assessed previously. In a prospective, randomized study, patients having undergone esophagectomy or gastrectomy for cancer received jejunal infusions of oligopeptide-based or whole-protein-based complete formulas (OPD and WPD, respectively) during two 9-h periods on 2 consecutive days in a crossover design. The OPD and WPD had identical energy compositions and amino acid profiles. Amino acid peripheral bioavailability (measurements of area under the curve of arterial blood concentrations), amino acid arteriovenous differences, and insulin and glucagon responses were measured. Amino acid peripheral bioavailability was higher (leucine: 54%, P < 0.01; essential amino acids: 48%, P < 0.01; total amino acids: 53%, P < 0.02) and peripheral appearance of amino acids was more homogeneous (variation around the calculated plateau of plasma leucine was 39% for OPD and 78% for WPD, P < 0.001) with the OPD than with the WPD. With the OPD, insulin stimulation was faster and plasma concentrations of leucine and insulin were correlated (r = 0.77, P < 0.01). The OPD led to a higher amino acid peripheral bioavailability than the corresponding WPD. These results could be useful for a better definition of clinical indications of semi-elemental diets.

Abdomen↗
PubMed1998

A randomized controlled trial of the influence of the mode of enteral ornithine alpha-ketoglutarate administration in burn patients.

To investigate appropriate mode and daily dose of enteral ornithine alpha-ketoglutarate (OKG) administration, 54 burn patients (total burn surface area: 20-50%) were included in a randomized controlled trial and assigned to receive either a supplement of OKG (10, 20 or 30 g/d) as bolus or continuous infusion, or a continuous infusion of an isonitrogenous amount of a soy protein mixture (Protil-1: 10, 20 or 30 g/d) in addition to their enteral diet. The influence of these treatments on clinical outcome and biological indices was evaluated. OKG administration significantly improved nitrogen balance and reduced 3-methylhistidine and hydroxyproline urinary elimination. This was associated with a gradual rise in plasma glutamine over time. Given as a bolus, OKG significantly improved wound healing, assessed both clinically [day of last graft: (mean +/- SEM) OKG bolus 23.7 +/- 2.1 d versus Protil-1, 39.9 +/- 9.9 d; P < 0.05] and by hydroxyproline excretion, and biological markers of nitrogen metabolism, and tended to reduce duration of enteral nutrition (P = 0.12). The higher catabolic status in the patients administered 20 g OKG/d at the onset of the study, despite randomization, precludes any definite conclusion (concerning the dose-effect relationship). However, based on 3-methylhistidine elimination, our data indicate a benefit of 30 g OKG/d administration over 10 g/d. This study further supports OKG supplementation in burn patients. In addition, this is the first trial based on objective data that favors bolus over continuous infusion of OKG in critically ill patients.

Adult↗
PubMed1998

Standardization of the lactulose-mannitol test in rats: application to burn injury.

Intestinal permeability can be assessed by measuring urinary mannitol and lactulose excretion after oral administration. This test may be useful as a tool in experimental studies to explore the effects of specific diets intended to promote the repair of the integrity of the gut barrier. In this study we standardized the lactulose-mannitol test in rats and applied it to a burned-rat model. The conditions were: oral administration of an isotonic mixture of 50 mg of mannitol and 66 mg of lactulose, followed by aseptic collection of urine over 4 h. The increase in the lactulose/mannitol ratio in burned rats was due to higher lactulose excretion. These results corroborate those obtained in burn patients and show that our model is suitable for further experiments on nutritional manipulation.

Animals↗
PubMed1998

[The pharmacist-nutritionist: myth or necessity?].

Nutrition has taken on great importance in the health considerations of the general population. To meet expectations many fields have been called to contribute. With his multi-disciplined training the Pharmacist can and should have an important role to play. Upstream, the agro-food industry has many opportunities to offer. Our knowledge of Genetics, Molecular Biology and Botany can be a great advantage. Nutriceuticals are at the interface of nutrition and medicine. They concerns foods which have preventative or curative properties for certain illnesses. Are we going to be able to integrate into this new concept? Administered in pharmacological doses certain nutriments are indeed drugs. The Pharmacist should have a better training in Nutrition in order to be able to do his job properly. In hospitals the Pharmacist dispenses and sometimes prepares solutions for parenteral nutrition, while the biologist participates in denutrition diagnosis.

France↗
PubMed1997

Measurement of glutamine synthetase activity in rat muscle by a colorimetric assay.

Glutamine synthetase catalyses the formation of L-Gln from L-Glu and NH4+. This enzyme also exerts a glutamyl-transferase activity that produces gamma-glutamyl-hydroxamate from Gln and hydroxylamine. This gamma-glutamyl-transfer reaction can be used to determine glutamine synthetase activity by colorimetric assay. This method has never been applied to rat muscle. The aim of this work was to study and optimize the glutamine synthetase assay conditions in rat muscle. Enzyme activity was linear with time of incubation (30 min at 37 degrees C) and linear with enzyme concentration in the incubation medium. The method was specific. In addition, this assay correlated well with a radiometric assay (y = 0.76x + 340, where x and y are the glutamine synthetase activities measured by radiometry and colorimetry respectively; r = 0.94; P = 0.05). Finally, no glutamine synthetase activity was found in muscles of rats treated with methionine sulfoximine, an inhibitor of glutamine synthetase, and activity dramatically rose in muscles from rats treated with dexamethasone, an activator of glutamine synthetase (in extensor digitorum longus: 2717 +/- 54 nmol/min/g protein in dexamethasone-treated rats versus 1228 +/- 114 nmol/min/g protein in control rats, P < 0.0001). In conclusion, the method presented here is accurate and reliable for measurement of glutamine synthetase activity in muscles.

Animals↗