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L Cynober

Publications and source records attributed to L Cynober.

At least 109 records · Page 6Linked to original sources

[Lysine and human nutrition].

Lysine is one of the 8 essential amino acids, i.e. it is not synthetized by the body. As such, lysine has been the object of controversy for numerous years with regard to recommended daily intake. Initially defined in terms of nitrogen balances, these values have been increased following studies based on stable isotopes. In parenteral nutrition, the supply of lysine is generally between 0.39 and 0.55 g/g of nitrogen, with the exception of products for babies (Primene, Vaminolac) in which values are higher. In the light of the metabolic pattern in pathologic situations and the speed of metabolization of perfused lysine, it would appear that lysine supplies are excessive. In certain states of malnutrition such as in patients with renal failure, large supplies of lysine are not only unnecessary but contra-indicated since this amino acid shows a certain degree of nephrotoxicity. Finally, in spontaneous nutrition, excessive lysine intake would appear to be atherogenic.

Humans↗

Rheumatoid arthritis modifies basal and insulin-mediated glucose uptake by human synoviocytes.

Basal and insulin-mediated glucose uptake were studied in human synovial cells. Cell cultures were established from samples of synovium obtained at synovectomy from patients with osteoarthritis (non-rheumatoid synovial cells, NRSC) or rheumatoid arthritis (rheumatoid synovial cells, RSC). Basal glucose uptake was significantly higher in RSC than in NRSC. NRSC were sensitive to insulin at near-physiological concentrations (10(-8)M), with maximal transport occurring after a 30-min. association time (27.2 +/- 2.0%, mean +/- SEM). Insulin did not stimulate significantly 2-déoxy-D-glucose uptake in RSC, regardless of the association time (up to 120 min.) or the insulin concentration (10(-10) to 10(-6) M). Treatment of NRSC with human recombinant interleukin-1 beta (IL-1 beta) enhanced glucose uptake to a level similar to basal uptake by RSC. These results suggest that autocrine production of IL-1 beta by RSC could be responsible for the higher basal glucose uptake by these cells.

Arthritis, Rheumatoid↗

Serum transthyretin levels in patients with burn injury.

We examined serum transthyretin levels after thermal injury in a longitudinal study of 61 patients with burn injury from day 2 to day 28 after trauma. All the patients had a maximal decrease in transthyretin levels between days 6 and 8. Transthyretin values remained lower during the recovery phase in patients who died than in patients who survived. In addition, persistently low transthyretin values were associated with sepsis in the survivors. Finally, transthyretin levels were only slightly dependent on the extent of the burn injury. These results emphasize the interest of transthyretin monitoring in patients with burn injuries.

Adolescent↗

Action of ornithine alpha ketoglutarate on DNA synthesis by human fibroblasts.

Ornithine alpha ketoglutarate (OKG) is largely used in clinical nutrition for its anabolic effects. However, the mechanism of its action remains questionable. We investigated the effect of OKG on the rate of DNA synthesis in human fibroblasts. The in vitro experimental procedure required to demonstrate in cell culture the anabolic effects of OKG observed in vivo was found to be glutamine-free and serum-poor medium with sparse cells. In these conditions, OKG induced a significant increase in [3H]thymidine incorporation compared to untreated control cells. This effect was dose-dependent and was observed in all the cultures tested. Taken individually, the two constituents of OKG, i.e. alpha KG and Orn, also showed a stimulatory effect, but did not demonstrate a dose-dependent response. Concomitant analysis of extracellular aminoacids showed in alpha KG-treated cultures an increase in glutamate and a decrease in aspartate, suggesting a cellular transamination of alpha KG. Glutamine, which is the preferential energetic substrate of fibroblasts, can be produced from glutamate and might play a role in the action of OKG. Moreover, OKG induced a rise in the cellular polyamine content. This, in association with the inhibitory effect on OKG action of difluoromethylornithine, a specific inhibitor of ornithine decarboxylase, suggests a link between the polyamine biosynthesis pathway and the anabolic effect of OKG.

Cells, Cultured↗

Amino acid metabolism in isolated perfused rat liver.

Conflicting evidence concerning hepatic amino acid (AA) metabolism in the isolated perfused rat liver (IPRL) led us to investigate the response of IPRL using perfusates with various AA contents. Perfusion (n = 4) with whole rat blood diluted in Krebs buffer (1:3, v/v) led to acute proteolysis on account of AA deprivation, as shown by the large release of AA (approximately 1400 mumoles in 120 min), especially branched-chain AA (BCAA) (e.g., Leu, 35.4 +/- 10.4 nmole.min-1.g-1 the first hour, 34.3 +/- 5.5 nmole.min-1.g-1 the second hour). In a first attempt to prevent proteolysis, livers (n = 4) were perfused with the previous medium supplemented with AA known for their antiproteolytic activity, at twice their physiological concentrations. Results during the first hour showed uptake of several AA (mainly alanine, glutamine, and proline), reduced release of BCAA (leucine, 12.5 +/- 6.3 nmole.min-1.g-1), and an increase in glucose and urea production. However, during the second hour, because of the use of a recirculating system, progressive AA depletion induced a reappearance of proteolysis. A two-step AA loading technique, i.e., the addition of antiproteolytic AA at the beginning of the perfusion and the addition of a balanced AA mixture at 60 min caused a further decrease in proteolysis during the 2 hr of perfusion (n = 6). Under these conditions, most AA were taken up by the liver with uptake values comparable to those observed in vivo.

Amino Acids↗

Action of ornithine alpha-ketoglutarate, ornithine hydrochloride, and calcium alpha-ketoglutarate on plasma amino acid and hormonal patterns in healthy subjects.

Ornithine alpha-ketoglutarate (OKG) has been useful as an adjuvant of enteral and parenteral nutrition. However, its metabolism and mechanism of action remain unclear although it is known that alpha-ketoglutarate (alpha KG) and ornithine (ORN) follow, in part, common metabolic pathways. Six fasting healthy male subjects underwent three separate oral load tests: (i) they received 10 g of OKG (i.e., 3.6 g of alpha KG and 6.4 g of ORN); (ii) 6.4 g of ORN as ornithine hydrochloride, and (iii) 3.6 g of alpha KG as calcium alpha-ketoglutarate. Blood was drawn 15 times over a five-hour period for measurements of plasma amino acids, alpha KG, insulin, and glucagon. After OKG and ORN administration, plasma ORN peaked at 60-75 min (494 +/- 91 and 541 +/- 85 mumol/L). The increase in plasma alpha KG was very small. OKG, alpha KG, and ORN all increased glutamate concentrations at 60 min (mean: +43%, +68%, +68%, respectively, p less than 0.05 compared to basal values). However, only OKG increased proline and arginine levels at 60 min (mean: +35%, p less than 0.01 and mean: +41%, p less than 0.05). Furthermore, glutamate, proline, and arginine concentrations correlated linearly with ornithine levels at 60 min. Finally, OKG increased insulinemia and glucagonemia (mean: +24% at 15 min, p less than 0.05 and +30% at 60 min, p less than 0.01, respectively). These data provide evidence that the combination of ORN and alpha KG modifies amino acid metabolism in a way which is not observed when they are administered separately. In addition, the OKG-mediated increase in insulin levels probably does not appear to result from a direct action of ORN on pancreatic secretion.

Administration, Oral↗

Perdialytic parenteral nutrition with lipids and amino acids in malnourished hemodialysis patients.

A 3-mo perdialytic parenteral nutrition (PDPN) regimen was tested in 26 malnourished adults receiving hemodialysis (HD). Subjects were randomly assigned to receive PDPN (n = 12) or not to receive it (n = 14). PDPN was intravenously infused three times a week during HD; each infusion was made up of 1.6 g fat/kg body wt, 0.08 g N/kg body wt, essential and nonessential amino acids, and glycyl-tyrosine. PDPN, together with a PDPN-induced increase in spontaneous eating, increased intakes from 30 +/- 8.4 kcal.kg body wt-1.d-1 (mean +/- SD) and 1 +/- 0.27 g protein.kg body wt-1.d-1 to 39 +/- 8.5 kcal.kg body wt-1.d-1 and 1.25 +/- 0.30 g protein.kg body wt-1.d-1. Compared with control subjects, PDPN patients were characterized by increases in body weight (P less than 0.01), arm-muscle circumference (P less than 0.02), serum transthyretin and albumin concentrations (P less than 0.05), interdialytic creatinine appearance (P less than 0.01), skin-test reactivity (P less than 0.02), plasma leucine (P less than 0.05) without modifications of other amino acids, and plasma apolipoprotein A-I (P less than 0.01) without significant changes in apolipoprotein B, cholesterol, triglyceride, and phospholipid concentrations. Thus, PDPN appeared to be effective and safe with respect to plasma lipids.

Adult↗

Efficiency of enteral nitrogen support in surgical patients: small peptides v non-degraded proteins.

In a prospective study, 12 intensive care patients, after abdominal surgery, received three alternate six-day courses of two enteral diets with identical nitrogen (0.3 g N/kg per day) and energy (60 kcal/kg per day) supply. The protein hydrolysate (PH) diet contained enzyme-hydrolysed casein and lactoserum (60% small peptides), while the non-degraded protein (NDP) diet contained a nitrogen source of similar amino acid composition, but in the form of non-degraded proteins. The patients were randomised to receive either PH-NDP-PH or NDP-PH-NDP. Parameters reflecting protein metabolism were assessed in the plasma, urine, and stomal effluent on days 1, 6, 12, and 18, three hours after stopping the nutrition (t0), and one hour after restarting it (t1). Comparisons of t1 and t0 values showed that 13 amino acids (including the eight essential amino acids) increased significantly with the protein hydrolysate diet, but only two increased with the non-degraded protein diet. Similarly, with protein hydrolysate, insulin-aemia at t1 was significantly higher than at t0 and correlated with plasma leucine, phenylalanine, alanine, and lysine concentrations. In addition, significant improvements in plasma albumin, transferrin, and retinol binding protein concentrations were seen with protein hydrolysate, together with a significant decrease in the plasma phenylalanine/tyrosine ratio and urinary 3-methylhistidine excretion. We conclude that in patients in intensive care after abdominal surgery enteral support containing small peptides is more effective than an equivalent diet containing whole proteins in restoring plasma amino acid and protein levels.

Adult↗

[Collection and processing of blood samples for amino acid assays].

Several parameters prior to amino acid assay per se can affect the results obtained. Such factors include, on the one hand, those related to sample collection (time and place) and, on the other hand, those related to the treatment of the sample (presence of anticoagulant, method of deproteinization, preservation and storage).

Amino Acids↗

[Hepatocyte transplantation. Treatment of hepatic encephalopathy. An experimental study in the rat].

The aim of this work was to assess the effect of intrasplenic liver cell transplantation (ILCT) on hepatic insufficiency induced by a terminolateral portocaval shunt (PCS) in rats. Thirty syngenic Wistar Furth rats were divided up into three groups: (a) rats with PCS (n = 10); (b) rats with PCS then ILCT of 10(7) liver cells isolated from the livers of syngenic rats (n = 10); (c) operated control rats (n = 10). Double-blind behavior tests were carried out two weeks, two months and six months after surgery. The spontaneous motor activity and the exploring activity of each rat were studied in automated cages fitted with infrared diodes. Each interruption of the infrared beam was automatically recorded by a computer and converted into an activity score (number/hour). The spontaneous motor activity and the exploring activity were poor in the rats with PCS. The ILCT significantly increased the spontaneous motor activity and the exploring activity 2 months and 3 weeks after transplantation, respectively. Three months after transplantation, the spontaneous motor activity and the exploring activity in the PCS/ILCT group were not significantly different from those of the control rats. This study shows that ILCT can correct the neurological signs of hepatic encephalopathy in an experimental model of chronic hepatic insufficiency, and suggests that ILCT may produce therapeutic benefits in chronic hepatic insufficiency.

Animals↗

Neutral amino acid transport in human synovial cells: substrate specificity of adaptative regulation and transinhibition.

Neutral amino acid transport was characterized in human synovial cells. The amino acids tested are transported by all three major neutral amino acid transport systems, that is, A, L, and ASC. The model amino acid 2-aminoisobutyric acid (AIB) was found to be a strong specific substrate for system A in synovial cells. When cells were starved of amino acids, the activity of AIB transport increased, reaching a maximum within 1 h. The stimulation of transport activity was not blocked by cycloheximide and would thus appear to be related to a release from transinhibition. Similarly, the decrease in the activity of AIB transport observed after the addition of alpha-methyl-aminoisobutyric acid (meAIB) appeared to be related to transinhibition. However, using a different approach, that is, amino acid starvation followed by incubation with 10 mM meAIB and transfer to an amino acid-free medium with or without cycloheximide supplementation, a clear increase in AIB uptake, due both to derepression and a release from transinhibition, was observed. Unlike human fibroblasts, the depression of system A in these synovial cells was not serum-dependent. The process of derepression was observed only after preloading with meAIB. Neither AIB nor alanine produced this phenomenon. Moreover, alanine preloading led to a large increase in AIB transport activity due to a release from transinhibition. These observations indicate that the process of derepression and release from transinhibition are specific to the substrates present in the culture medium prior to amino acid starvation.

Alanine↗

Influence of enterally administered ornithine alpha-ketoglutarate on hormonal patterns in burn patients.

Plasma concentrations of glucose, insulin, C-peptide, glucagon, cortisol and hGH were measured in burn patients (mean burn surface area 21 per cent) treated or not with ornithine alpha-ketoglutarate (OKG). An increase in basal values of glucose, insulin, C-peptide and cortisol was demonstrated in both groups, whereas hGH values diminished. OKG modified neither insulin nor hGH values 24 h after its enteral administration nor insulin levels within the first 4 h after intake. On the other hand, 60 min after enteral nutrition was restarted the hyperglycaemia observed in untreated subjects was reduced by OKG whereas a hyperinsulinism was observed in both groups. These results suggest that: (i) the anticatabolic/anabolic action of OKG in burn patients is not mediated by insulin or hGH, (ii) OKG probably induces an increase in glucose tolerance in burn patients, in whom there is a state of insulin resistance. The mechanism of this action requires further study.

Adolescent↗

Sensitivity of cultured fibroblasts to human, bovine and porcine insulins.

We have studied the effects of human, bovine and porcine insulin on sugar transport by cultured chicken embryo fibroblast monolayers. For a 30 min. association time, human and bovine insulin at a concentration of 5.10(-8) M stimulated 2-deoxy-D-glucose uptake. (respectively by an average 58 p.cent and 55 p.cent over basal). Porcine insulin was less potent since a concentration of 5.10(-7) M was necessary to obtain similar stimulation. Moreover, the maximal effect of porcine insulin occur only after 60 min. association time instead of 30 min. for the other peptides. The differences between the effects of insulin from different sources is related to species-dependent differences in their structure.

Animals↗

Modulation of insulin action on 2-deoxyglucose uptake by chloroquine in chick embryo fibroblasts.

Blazar et al. recently found that chloroquine therapy decreased intravenous insulin requirements in a case of extreme insulin resistance. However, no relationship has been shown to exist between insulin degradation and the stimulation of glucose uptake. In this study we investigate the action of insulin on glucose uptake by the ability of this hormone to stimulate 2-deoxyglucose. The effect on alpha-aminoisobutyrate uptake, which is known to be insulin sensitive, is also investigated. Cell-associated 125I-labeled insulin and trichloroacetic acid-soluble and -precipitable substances were measured in parallel. Chloroquine increased insulin-stimulated uptake of 2-deoxyglucose and alpha-aminoisobutyrate. Three hours were required for this effect to appear, and it did not depend on DNA synthesis. Chloroquine also increased cell-associated insulin and slightly decreased the percentage of trichloroacetic acid-soluble products. Methylamine affected neither nutrient uptake processes nor insulin binding and degradation; however, it did abolish the effect of chloroquine on these parameters. These data suggest that in chick embryo fibroblasts a relationship may exist between the increase in undegraded cell-associated insulin and the ability of the hormone to stimulate sugar and amino acid uptake.

Aminoisobutyric Acids↗