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L Cynober

Publications and source records attributed to L Cynober.

At least 19 recordsLinked to original sources

The equivocal metabolic response to endotoxaemia in type 2 diabetic and obese ZDF rats.

AIMS/HYPOTHESIS: The metabolic and endocrine disturbances associated with obesity and type 2 diabetes may impair the normal metabolic response to injury. Our objective was to investigate amino acid metabolism in endotoxaemic type 2 diabetic obese rats. MATERIALS AND METHODS: A metabolic study was performed over 4 days using male Zucker diabetic fatty (ZDF) rats (fa/fa) and lean littermates (fa/+) divided into three groups: ad libitum-fed groups which underwent no treatment, lipopolysaccharide (LPS)-treated groups receiving E. coli LPS by i.p. injection, and pair-fed groups to the respective LPS groups. We evaluated the effect of endotoxaemia on body weight, food intake and tissue weights. Nitrogen loss and muscular proteolysis were measured daily by determination of urinary 3-methylhistidine (3-MH) excretion. Plasma, intestine and muscle amino acid levels were measured. RESULTS: The data showed that ad libitum-fed ZDF rats had lower plasma arginine and glutamine levels than ad libitum-fed control rats. Compared with control rats, the LPS-treated ZDF rats presented lower thymic involution, a lower 3-MH:creatinine ratio and higher cumulative nitrogen balance. CONCLUSIONS/INTERPRETATION: Against our working hypothesis, ZDF rats did not show an impaired metabolic response, and even appeared to be less sensitive to the stress.

Amino Acids↗

Citrulline modulates muscle protein metabolism in old malnourished rats.

Protein energy malnutrition is common in the elderly, especially in hospitalized patients. The development of strategies designed to correct such malnutrition is essential. Our working hypothesis was that poor response to nutrition with advancing age might be related to splanchnic sequestration of amino acids, which implies that fewer amino acids reach the systemic circulation. Administration of citrulline, which is not taken up by the liver, can offer a means of increasing whole body nitrogen availability and, hence, improve nutritional status. Thirty old (19 mo) rats were submitted to dietary restriction (50% of food intake) for 12 wk. They were randomized into three groups: 10 rats (R group) were killed and 20 others refed (90% of food intake) for 1 wk with a standard diet (NEAA group) or a citrulline-supplemented diet (Cit group). Before being killed, the rats were injected with [(13)C]valine, and the absolute protein synthesis rate (ASR) was measured in the tibialis using the flooding-dose method. When the rats were killed, the tibialis was removed for protein content analysis. Blood was sampled for amino acid and insulin analysis. The standard diet did not have any effect on protein synthesis or on the protein content in the muscle. Citrulline supplementation led to higher protein synthesis and protein content in muscle (117 +/- 9, 120 +/- 14, and 163 +/- 4 mg/organ for protein content in R, NEAA, and Cit groups, P < 0.05). The ASR were 0.30 +/- 0.04, 0.31 +/- 0.04, and 0.56 +/- 0.10 mg/h in the three groups, respectively (R and NEAA vs. Cit, P < 0.05). Insulinemia was significantly higher in the Cit group. For the first time, a realistic therapeutic approach is proposed to improve muscle protein content in muscle in frail state related to malnutrition in aging.

Age Factors↗

Glucose-lipid ratio is a determinant of nitrogen balance during total parenteral nutrition in critically ill patients: a prospective, randomized, multicenter blind trial with an intention-to-treat analysis.

OBJECTIVE: Protein sparing, the major goal of nutritional support, may be affected by the glucose/lipid ratio. This study in critically ill patients compared the efficacy and tolerance of two isocaloric isonitrogenous total parenteral nutritions (TPN) having different glucose/lipid ratios. DESIGN: Multicentric prospective randomized study. PATIENTS: 47 patients with SAPS I score higher than 8 and requiring exclusive TPN. INTERVENTIONS: Patients received glucose/lipid ratios of 50/50 or 80/20. For 7 days all patients received 32 glucidolipidic kcal/kg and 0.27 g/kg nitrogen daily. All-in-one bags were prepared using industrial mixtures and a fat emulsion. MEASUREMENTS AND RESULTS: We determined TPN efficacy by nitrogen balance, urinary 3-methylhistidine/creatinine ratio, transthyretin and tolerance by glycemia, and liver enzymes. After controlling for five variables with significant effects, patients receiving the 50/50 ratio during TPN had significantly higher nitrogen balance than those receiving the 80/20 ratio. The daily difference in mean nitrogen sparing effect in favor of the latter group was 1.367 g (95% CI 0.0686-2.048). Glycemia on day 4 and gamma-glutamyltranspeptidase on day 8 were higher in group receiving the the 80/20 ratio. CONCLUSIONS: In critically ill patients TPN at a glucose/lipid ratio of 80/20 ratio induces a small nitrogen sparing effect compared to the ratio of 50/50, at the expense of poorer glycemic control. The clinical significance is unclear.

Critical Care↗

Almost all about citrulline in mammals.

Citrulline (Cit, C6H13N3O3), which is a ubiquitous amino acid in mammals, is strongly related to arginine. Citrulline metabolism in mammals is divided into two fields: free citrulline and citrullinated proteins. Free citrulline metabolism involves three key enzymes: NO synthase (NOS) and ornithine carbamoyltransferase (OCT) which produce citrulline, and argininosuccinate synthetase (ASS) that converts it into argininosuccinate. The tissue distribution of these enzymes distinguishes three "orthogonal" metabolic pathways for citrulline. Firstly, in the liver, citrulline is locally synthesized by OCT and metabolized by ASS for urea production. Secondly, in most of the tissues producing NO, citrulline is recycled into arginine via ASS to increase arginine availability for NO production. Thirdly, citrulline is synthesized in the gut from glutamine (with OCT), released into the blood and converted back into arginine in the kidneys (by ASS); in this pathway, circulating citrulline is in fact a masked form of arginine to avoid liver captation. Each of these pathways has related pathologies and, even more interestingly, citrulline could potentially be used to monitor or treat some of these pathologies. Citrulline has long been administered in the treatment of inherited urea cycle disorders, and recent studies suggest that citrulline may be used to control the production of NO. Recently, citrulline was demonstrated as a potentially useful marker of short bowel function in a wide range of pathologies. One of the most promising research directions deals with the administration of citrulline as a more efficient alternative to arginine, especially against underlying splanchnic sequestration of amino acids. Protein citrullination results from post-translational modification of arginine; that occurs mainly in keratinization-related proteins and myelins, and insufficiencies in this citrullination occur in some auto-immune diseases such as rheumatoid arthritis, psoriasis or multiple sclerosis.

Animals↗

Effects of an immune-enhancing diet in endotoxemic rats.

OBJECTIVE: This work compared the nutritional efficiency of a recently available enteral formula enriched with arginine, omega-3 fatty acids, and antioxidants and supplied nitrogen as peptides (Crucial, Nestle Clinical Nutrition) with that of a standard polymeric formula (Sondalis HP, Nestle Clinical Nutrition) in endotoxemic rats. METHODS: Male Wistar rats (209 +/- 2 g) underwent catheter gastrostomy and received Sondalis HP until they recovered their preoperative weight. At that time (day 0), an endotoxemic shock was induced by an intraperitoneal injection of lipopolysaccharide (Escherichia coli, 8 mg/kg) and rats then received 290 kcal x kg(-1) x d(-1) and 3.29 g of nitrogen x kg(-1) x d(-1) in the form of Crucial (IED group, n = 7) or Sondalis HP (S group, n = 6) for 3 d. Another group underwent no treatment and was fed ad libitum (AL group). Rats were killed on day 3. Results are presented as mean +/- standard error of the mean (analysis of variance and Newman-Keuls test). RESULTS: The endotoxemic shock induced a weight loss in group S on days 1 and 2 and a weight gain in group IED (-3.5 +/- 1.3 g in group S versus +6.0 +/- 2.2 g in group IED, P < 0.05). In the same way, atrophy of extensor digitorum longus muscle was observed in group S, whereas wasting was limited in group IED (102 +/- 4 mg in group IED versus 90 +/- 3 mg in group S versus 119 +/- 3 mg in group AL, P < 0.05). Muscular atrophy was associated with muscular glutamine depletion and correlated with hyperphenylalaninemia (R = 0.60), with the latter being blunted in group IED (57 +/- 1 microM/L in group AL versus 77 +/- 4 microM/L in group S versus 66 +/- 2 microM/L in group IED, P < 0.05). No difference was observed between the experimental groups of endotoxemic rats with respect to nitrogen balance, urinary excretion of 3-methyl histidine, or total tissue protein content. CONCLUSION: Crucial counteracts injury-mediated weight loss, extensor digitorum longus muscle atrophy, and hyperphenylalaninemia in endotoxemic rats.

Analysis of Variance↗

Use of oral supplements in malnourished elderly patients living in the community: a pharmaco-economic study.

BACKGROUND & AIMS: Inadequate nutritional support in elderly patients is likely to be responsible for increased morbidity and increased associated costs. Conversely prescribing oral supplements to ensure sufficient protein and energy intake should be beneficial. Even though this claim makes sense there is a lack of objective data to support the evidence. The objective of the present study was to assess the cost of malnutrition and related comorbidities among elderly patients living in the community and to determine the impact of nutritional support practice on these outcomes. METHODS: Observational, prospective, longitudinal, cohort study with a 12 months follow-up conducted with 90 general practitioners in France. Two groups of physicians were selected based on historical prescribing practice: group 1 with rare and group 2 with frequent prescription of oral nutrition supplements. The resulting study population was 378 elderly malnourished patients aged over 70, living in the community, either at home or in institutions. Nutritional status at baseline was determined using the Mini Nutritional Assessment (MNA) scale. Main outcome measures were nutritional status, malnutrition-related comorbidities and medical care consumption. RESULTS: Populations in the two groups of patients were balanced for age, gender, weight and body mass index but differed significantly in terms of housing status (P < 0.005) and nutritional status (P < 0.001). After adjustment for baseline characteristics, MNA improved within both groups over time but improvement was significantly higher in group 2 than in group 1 (P < 0.01). The adjusted cost per patient of hospital care (EUR -551), nursing care (EUR -145) and other medical care was significantly reduced in group 2 as compared to group 1, with cost savings of EUR -723 per patient (90% CI: EUR -1.444 to EUR -43). Including the costs related to nutritional products, the total cost savings per patient attributable to nutrition support were EUR -195 (90% CI: EUR -929 to EUR +478). CONCLUSION: Appropriate nutrition support can address the problem of malnutrition among elderly individuals living in the community and may contribute to reduce the costs of health care.

Aged↗

Citrulline increases arginine pools and restores nitrogen balance after massive intestinal resection.

OBJECTIVE: Arginine supplementation seems logical in situations where this amino acid becomes essential, for example after massive intestinal resection. Arginine is taken up and metabolised by the liver to a large extent and its supplementation is potentially unsafe. Citrulline is not captured by the liver and passes freely to the kidneys where it is metabolised to arginine, and so is a good candidate to generate arginine and thereby improve nutritional status. METHODS: Twenty four rats were assigned to four groups: citrulline, arginine, control, and sham. The sham group underwent transection and the three other groups resection of 80% of the small intestine. All rats were fed by enteral nutrition and its composition was as follows: supplementation with citrulline in the citrulline group, supplementation with arginine in the arginine group, and standard polymeric enteral nutrition in the control and sham groups. All groups received isonitrogenous nutrition and citrulline and arginine intakes were equimolar in their respective groups. After 10 days, the rats were sacrificed. RESULTS: Arginine concentration was higher (p<0.05) in plasma and muscle in the citrulline group than in the three other groups. Plasma levels of arginine were 110 (12), 79 (7), 167 (22), and 228 (13) mumol/l in the sham, control, arginine, and citrulline groups respectively. Arginine concentrations in the gastrocnemius were: 0.15 (0.02), 0.16 (0.02), 0.40 (0.05), and 0.94 (0.20) mumol/g, respectively. Citrulline preserved nitrogen balance in resected rats but not in arginine supplemented rats (mean J10: 2.27 (0.29), 1.67 (0.15), 1.98 (0.29), and 2.43 (0.41) g/24 hours in the sham, control, arginine, and citrulline groups, respectively). CONCLUSION: Supplementing the diet with citrulline is a very efficient means of increasing arginine levels and improving nitrogen balance after massive intestinal resection. The results of this study form a strong rationale for citrulline supplementation in these patients.

Amino Acids↗

Metabolic pathways implicated in the kinetic impairment of muscle glutamine homeostasis in adult and old glucocorticoid-treated rats.

An impairment of muscle glutamine metabolism in response to dexamethasone (DEX) occurs with aging. To better characterize this alteration, we have investigated muscle glutamine release with regard to muscle glutamine production (net protein breakdown, de novo glutamine synthesis) in adult and old glucocorticoid-treated rats. Male Sprague-Dawley rats (3 or 24 mo old) were divided into seven groups: three groups received 1.5 mg/kg of DEX once a day by intraperitoneal injection for 3, 5, or 7 days; three groups were pair fed to the three treated groups, respectively; and one control group of healthy rats was fed ad libitum. Muscle glutamine synthetase activity increased earlier in old rats (day 3) than in adult rats (day 7), whereas an increase in muscle glutamine release occurred later in old rats (day 5) than in adult DEX-treated rats (day 3). Consequently, muscle glutamine concentration decreased later in old rats (day 5) than in adults (day 3). Finally, net muscle protein breakdown increased only in old DEX-treated rats (day 7). In conclusion, the impairment of muscle glutamine metabolism is due to a combination of an increase in glutamine production and a delayed increase in glutamine release.

Aging↗

Advances in analytical techniques: from biochemical assessment of nutritional status to the identification of controlling factors.

Analytical techniques for the biochemical assessment of nutritional status have been the focus of continuing interest at ESPEN over the years. All the congress proceedings were scrutinized to prepare this review. A total of 274 abstracts were found to be relevant to the topic. Fifty-six of these were selected as especially representative of the topic and are referenced. Eighty-seven additional papers of special interest are mentioned in the text with the details necessary to find them easily in the Clin. Nutr. Supplement where they were published. Methods involving stable isotopes were not considered here because these are discussed elsewhere.

Amino Acids↗

Effects of dipeptide administration on hypoglycaemic counterregulation in type 1 diabetes.

OBJECTIVES: To investigate if a dipeptide made of glutamine and alanine is able to contribute to the recovery from insulin-induced hypoglycaemia in type 1 diabetes. RESEARCH DESIGN AND METHODS: Fifteen adult type 1 patients were randomly assigned to study group (n=7): intravenous infusion of 20 g Dipeptiven in normal saline (i.e., 8 g alanine and 13 g glutamine), or control group (n=8): same infusion, normal saline only. A 150 min gradual hypoglycaemic hyperinsulinemic clamp was administered after 2 h of infusion. Counterregularory hormones, symptoms, and cognitive function (4 choice reaction test) were regularly measured during the study. RESULTS: Blood glucose and glucose infusion rates were similar in the 2 groups. Circulating levels of alanine and glutamine peaked at 90 min and remained elevated throughout the test. This was associated with significant differences in: glucagonemia 107 +/- 20 vs 58 +/- 8 pg/ml, and neuroglycopenic symptoms scores: 7 +/- 3 vs 18 +/- 13, at t 150 min, in study and control group, p<0.05. Dysautonomic symptoms, cognitive tests as well as epinephrine, norepinephrine, cortisol and growth hormone were similar between groups. CONCLUSION: Intravenous infusion of a dipeptide made of alanine and glutamine is capable to reactivate glucagon secretion during insulin-induced hypoglycaemia and to reduce hypoglycaemic symptoms.

Adult↗

Effect of apoE/ATP-containing liposomes on hepatic energy state.

BACKGROUND/AIMS: ATP-containing liposomes partially prevent ATP depletion in the cold-stored liver. As hepatocytes can specifically bind apoE, we investigated whether the addition of apoE to large (200 nm) ATP-containing liposomes increases their uptake by the liver and further improves hepatic energy stores. METHODS: Livers from fasted male Hartley guinea-pigs (231 +/- 3 g) were perfused for 90 min under our standard conditions (Control, n = 6) or after a single bolus addition of plain liposomes (Lip, n = 6), ATP (5 micromol)-containing liposomes (ATP-Lip, n = 6) or apoE/ATP-containing liposomes (0.8 or 8mg apoE/g phospholipids; apoE1-Lip and apoE10-Lip, respectively, n = 6 in each group). Liposome uptake and its impact on energy and nitrogen metabolism were studied. RESULTS: At its highest concentration, apoE significantly increased liposome uptake (apoE10-Lip: - 9.17 +/- 0.69 vs apoE1-Lip: - 6.18 +/- 0.44 vs ATP-Lip: - 6.40 +/- 0.88 nmol min(-1) g(-1) P < 0.05). This was associated with a significant increase in intrahepatic ATP (apoE10-Lip: 1033 +/- 137 vs apoE1-Lip: 811 +/- 98 and ATP-Lip: 648 +/- 36 nmol g(-1); P < 0.05), which was restored to its level in non-perfused livers. Hepatic viability and nitrogen metabolism were not affected. CONCLUSIONS: Hepatic ATP content being a key factor in the maintenance of liver graft function, apoE/ATP-containing liposomes should be useful in liver preservation for transplantation.

Adenosine Triphosphate↗

Hepatic preservation, liposomally entrapped adenosine triphosphate and nitric oxide production: a study of energy state and protein metabolism in the cold-stored rat liver.

BACKGROUND: Liposomally entrapped adenosine triphosphate (ATP) has been demonstrated to improve energy state and function of the cold-stored liver. The increased nitrite release associated with liposome administration led us to investigate the interactions between liposome supply and nitric oxide (NO) production through the use of L-NAME, a non-selective inhibitor of NO synthesis. METHODS: Twenty-four livers from fasted rats were stored for 18 h at +4 degrees C in University of Wisconsin solution directly (control group) or after infusion with ATP-containing liposomes (Lip-ATP), L-NAME (L-NAME) or both (Lip-ATP-L-NAME). Metabolic fluxes, cell volume and energy state were studied during reperfusion. RESULTS: After storage, nitrite release was increased by 61% in the Lip-ATP group, markedly decreased in the Lip-ATP-L-NAME group and almost abolished in the L-NAME group. The ATP content was increased by 20% in the Lip-ATP group (P < 0.05 versus control) and on reperfusion this was associated with an increase in cell volume (17%; P < 0.05) and a decrease in branched-chain amino acid release (21%; P < 0.01). The simultaneous addition of L-NAME did not affect these results, but induced a large (6-fold) increase in glucose production, possibly related to the metabolism of glycerol supplied by the liposomes. In the L-NAME group, global amino acid release was 50% lower and was associated with a dramatic decrease in urea production while the energy state deteriorated rapidly. CONCLUSIONS: The improvement in energy state and anabolic cell swelling induced by ATP-containing liposomes seems to be independent of NO synthesis. On the other hand, inhibition of NO synthesis appears to exert a detrimental effect on the liver, presumably through the decrease in hepatic energy content.

Adenosine Triphosphate↗

Nutritional depletion in patients on long-term oxygen therapy and/or home mechanical ventilation.

The purpose of this study was to estimate the prevalence of malnutrition in outpatients on long-term oxygen therapy or home mechanical ventilation, to determine the relationships between malnutrition and impairment/disability and smoking and also to identify relevant tools for routine nutritional assessment. In 744 patients (M:F 1.68, aged 65+/-15 yrs) with chronic obstructive pulmonary disease (COPD, 40%), restrictive disorders (27%), mixed respiratory failure (15%), neuromuscular diseases (13%) and bronchiectasis (5%), body mass index (BMI), fat-free mass (FFM), serum albumin, transthyretin, 6-min walking test, forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and blood gases were recorded. FFM was the most sensitive parameter for detecting malnutrition, being abnormal in 53.6% of patients, while BMI was <20 in 23.2%, serum albumin <35 g x L(-1) in 20.7%, and serum transthyretin <200 mg x L(-1) in 20%. FFM depletion predominated in neuromuscular, bronchiectasis and restrictive disorders. BMI and FFM were correlated with FEV1, FVC and 6-min walking test. In multivariate analysis a BMI<20 was related to FEV1 and smoking habits, and a low FFM to smoking, FEV1 and female sex. Malnutrition is highly prevalent in home-assisted respiratory patients and is related to causal disease, forced expiratory volume in one second, smoking and disability. Fat-free mass appeared to be the most sensitive and relevant nutritional parameter according to impairment and disability.

Aged↗

Dexamethasone treatment induces long-lasting hyperleptinemia and anorexia in old rats.

Aging brings poor adaptation to stress, the causes of which remain unclear. We previously reported impairment of nitrogen metabolism in glucocorticoid-treated old rats due to profound anorexia. Here we investigated whether leptin, a satiety hormone, was implicated in impaired adaptation to stress. Plasma glucose and insulin levels, which are known to modulate leptin secretion, were also studied. Adult (3 months, n = 18) and aged (24 months, n = 18) rats were treated with dexamethasone (DEX) (1.5 mg/kg/d, intraperitoneal [IP] injection) for 3, 5, and 7 days. Results were compared with ad libitum (n = 12) and pair-fed groups, receiving intraperitoneal saline injection, for each age (n = 6 per group). Transitory anorexia was observed in adult rats (day 3 to day 5), whereas anorexia persisted in aged rats until day 7. This anorexia was associated (r = -.65, P <.05) with an elevated constant hyperleptinemia. In contrast, hyperleptinemia was moderate and reverted rapidly to basal values by day 5 in adult rats. The time course of plasma insulin and glucose levels was similar in old and adult rats, except for marked hyperglycemia noted in aged animals. In old stressed rats, DEX treatment induces an anorexia, which is concomitant to an increase in serum leptin levels. Thus, leptin may be implicated in the poor adaptation to stress of aged compared with adult rats.

Aging↗