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Biomedical subjects

L Cynober

Publications and source records attributed to L Cynober.

At least 91 records · Page 5Linked to original sources
PubMed1995

Metabolism of alpha-ketoisocaproic acid in isolated perfused liver of cirrhotic rats.

To determine the hepatic fate of alpha-ketoisocaproate (KIC) in cirrhosis, six groups of isolated rat livers were perfused with 0, 0.5, 1 (with or without alpha-[1-14C]KIC), 2, and 5 mM KIC; control livers from healthy rats were studied in parallel under similar conditions. KIC was rapidly removed by the normal livers, whereas uptake was lower in the cirrhotic livers at all concentrations tested (at 2 mM, 4.04 +/- 0.33 vs. 6.32 +/- 0.58 mumol/min; P < or = 0.05). The transamination pathway, evaluated by leucine exchanges, was more important in the cirrhotic livers (25.4 vs. 6.8% in controls at 2 mM). The incorporation of alpha-[1-14C]KIC in proteins of cirrhotic liver was increased compared with controls (0.25 +/- 0.04% of alpha-[1-14C]KIC was incorporated in proteins excreted in perfusate vs. 0.20 +/- 0.04 in controls; P < or = 0.05). In addition, a line of evidence suggests that glutamine rather than glutamate is the N donor for leucine synthesis from KIC. The decarboxylation pathway evaluated by beta-hydroxybutyrate production and by 14CO2 release from alpha-[1-14C]KIC was reduced, respectively, by 40-85% (according to KIC dose) and by 24% at 90 min in cirrhotic livers compared with healthy livers. These results indicate a dramatic modification of KIC metabolism in the cirrhotic liver; its uptake by the liver is decreased and its incorporation into proteins is increased via an enhancement of transamination to leucine, probably as a consequence of an inhibition of branched-chain keto acid dehydrogenase.

Animals↗
PubMed1994

Plasma fibronectin and angiotensin-converting enzyme: markers of primary pulmonary injury in burn patients.

Plasma fibronectin (FBN) and angiotensin I-converting enzyme (ACE) were prospectively measured in 50 burn patients from the day of admission to day 28 after the trauma with the aim of finding biochemical markers of pulmonary injury by smoke inhalation. Patients were divided into three groups on the basis of fiberoptic bronchoscopy results (group I: healthy lungs; group II: burned lungs; group III: infected lungs). A decrease in FBN concentrations was observed in the three groups but was larger in group II than in the other groups, especially at day 2 (P < 0.05). A similar profile was observed for plasma ACE activity. Factors other than lung injury may influence plasma FBN and ACE levels, in particular the burned body surface area, an acute event such as septicemia, or outcome. However, repeated measurements of both markers could help in the assessment of lung injury in the follow-up of burn patients.

Adult↗
PubMed1994

Independent and combined actions of interleukin-1 beta, tumor necrosis factor alpha, and glucagon on amino acid metabolism in the isolated perfused rat liver.

Conflicting reports concerning the hepatic effects of interleukin-1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF alpha) in the metabolic response to injury led us to investigate the influence of physiological concentrations of these cytokines on amino acid metabolism in the isolated perfused rat liver. IL-1 beta was ineffective at a concentration of 1 ng/mL, whereas TNF alpha (0.7 ng/mL) reduced the uptake of some of the main gluconeogenic amino acids (alanine, -55.3 +/- 4.9 v -72.9 +/- 13.7 nmol.min-1.g-1 in controls, P < .05) without affecting urea synthesis. TNF alpha increased glucose uptake by 237% and inhibited that of free fatty acids (-1.6 +/- 1.4 v -9.9 +/- 6.7 nmol.min-1.g-1 in controls, P < .05). IL-1 beta and TNF alpha potentiated glucagon-induced total amino acid uptake by 56% and 87%, respectively. They also affected glucagon-activated gluconeogenesis, leading to an initial potentiation of glucose release. Thereafter, IL-1 beta inhibited glucagon action, leading to an hepatic uptake of glucose. These results indicate that (1) in the conditions of the study, IL-1 beta has no direct effect on hepatic amino acid exchanges and utilization; (2) TNF alpha which exerted an inhibitory effect on these parameters, could be involved in the reduced amino acid exchanges during the end stage of sepsis; (3) the TNF alpha-induced increase in glucose uptake could be related to an inhibition of gluconeogenesis and/or to the activation of glucose utilization by Kupffer cells; (4) IL-1 beta and TNF alpha both potentiate the action of glucagon on hepatic amino acid uptake and utilization; and (5) complex interactions between Kupffer cells and hepatocytes on the one hand and between cytokines and hormones on the other hand could account for the differences in hepatic metabolism according to the stage of the response to injury.

Amino Acids↗
PubMed1994

Ornithine alpha-ketoglutarate limits muscle protein breakdown without stimulating tumor growth in rats bearing Yoshida ascites hepatoma.

The growth of the Yoshida ascites hepatoma AH130 (YAH) is associated with early wasting, depletion of intracellular amino acid pools, and a pronounced activation of protein degradation in skeletal muscle of the host animal. Ornithine alpha-ketoglutarate (OKG) is used in the treatment of hypercatabolic states, and it has been suggested that it may improve nitrogen balance through repletion of free amino acid pools and suppression of protein catabolism. In cancer, OKG might similarly improve host nutritional status or stimulate tumor growth if its metabolites are limiting for tumor growth. Enteral supplementation with OKG was investigated in Sprague-Dawley rats bearing YAH. Tumor-bearing rats were compared with ad libitum- and pair-fed controls. Rats received OKG (3.4 to 4.0 g/kg body weight/d) or an equal amount of nitrogen as glycine (n = 8 in each group) for 5 days. Tumor implantation decreased cumulative food intake (-40%), host weight (-6%), skeletal muscle weight, and free amino acid levels in muscle and plasma. Muscle protein balance was estimated in vitro; decreased protein synthesis (-30%) and increased proteolysis (+113%) were observed in epitrochlearis muscles (EPI) of YAH-bearing rats compared with control groups. OKG had no effect on the wet weight (10 +/- 1 g) and nitrogen content of the tumor, or on free amino acid levels in the tumor. In tumor-bearing rats, OKG improved muscle protein balance by reducing breakdown by 33% and overall amino acid release of incubated EPI by 46%.

Amino Acids↗
PubMed1994

Biochemical assessment of nutritional status in patients with chronic obstructive pulmonary disease and acute respiratory failure on admission to an intensive care unit.

Although chronic obstructive pulmonary disease (COPD) is associated with weight loss and malnutrition, there is a paucity of relevant data on COPD patients with acute respiratory failure (ARF). We studied 30 consecutive patients on the day of admission to our intensive care unit for ARF. In addition to a clinical work-up, the following biochemical parameters were determined: markers of nutritional status (albumin - ALB, transferrin - TRF, transthyretin - TTR, retinol binding protein - RBP, fibronectin), inflammation (C-reactive protein - CRP, alpha(1) glycoprotein acid - alpha(1)GPA) and catabolism (plasma phenylalanine - PHE, urinary 3-methylhistidine - 3-MH). Values were expressed as mean +/- SD and compared to those of 10 healthy subjects matched for age. COPD-ARF patients had a poor protein status (ALB = 30 +/- 5 vs 42 +/- 3 g.l(-1); TTR = 118 +/- 75 vs 251 +/- 43 mg.l(-1); RBP = 23 +/- 12 vs 46 +/- 8 mg.l(-1); p < 0.001), were hypercatabolic (3-MH Cr = 31 +/- 12 vs 22 +/- 7 mumol.mmol Cr (-1); PHE = 62 +/- 27 vs 46 +/- 10 mumol.l(-1); p < 0.001) and inflamed (CRP = 68 +/- 50 vs 12 +/- 5 mg.l(-1); alpha(1)GPA = 1.2 +/- 0.4 vs 0.5 +/- 0.1 g.l(-1); p < 0.001). Severity of the disease correlated with short half-life proteins and protein catabolism markers but not with inflammation markers. Considering ALB, TTR, RBP, the 3- MH Cr ratio and PHE values, the 30 COPD patients fell into 3 groups: chronic malnutrition (n = 7), acute malnutrition (n = 2), and acute + chronic malnutrition (n = 18). 3 patients had normal nutritional status. We conclude that an assessment of nutritional status at admission to intensive care units could contribute towards a rapid formulation of specific nutritional therapy.

Journal Article↗
PubMed1994

[Nutrition proteins and muscular catabolism in severely burnt patients. Comparative effects of small peptides or free amino acids].

The beneficial effects of high caloric and protein enteral diet on wound healing and prevention of infection in severely burned patients is well documented. However, the relative proportion of each nutrient and especially the form of nitrogen supply have not yet been clearly established. The aim of this study was to compare, in severely burned patients, the efficiency of a partial protein hydrolysate and free amino acid formula during a 15-day enteral feeding. Twenty burned patients ranging in age from 18 to 67 years with a mean burn size of 40 +/- 12% of total body surface area, of which 31 +/- 14% was deep dermal, were studied prospectively and randomised in two groups. Group A received the free amino acid diet which was obtained by hydrolysis of the protein hydrolysate given to Group B (60% small peptides). All diets contained a nitrogen source of similar amino acid composition. Nitrogen balance was measured daily and serum protein concentrations were determined on days 0, 4, 8, 11 and 15. Anthropometric parameters, urinary 3 methylhistidine/creatinine ratio and plasma amino acid concentration were assessed on days 0, 8 and 15. Daily and cumulative nitrogen balance at D15 did not differ between the two groups. In group A, the circulating visceral proteins increased at all times of the study without decrease of acute phase reactant, whereas only transthyretin and retinol binding protein increased at D11 and D15 with a significant decrease of C-reactive protein at the same time in the other group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Growth retardation in children receiving long-term total parenteral nutrition: effects of ornithine alpha-ketoglutarate.

We evaluated the effect of ornithine ketoglutarate (OKG) in reversing abnormal growth in six prepubertal children receiving total parenteral nutrition (TPN) for 5-10 y. They were 1-4 SDs below their expected 50th percentile for height. The energy and nitrogen intakes were unchanged from 8 mo before the beginning of the study until its completion. Two consecutive periods of 5 mo each were studied. OKG (15 g) was added to the parenteral solution during the first period (OKG+) but not during the second period (OKG-). Height velocity (HV) increased (P < 0.05) from a median of 3.8 cm/y to 6.45 cm/y (range 1.8-6.7) during the OKG+ period, and decreased (P < 0.05) to a median of 3.65 cm/y in the OKG- period. Plasma concentrations of insulin-like growth factor 1 (IGF1), glutamine, and glutamate increased (P < 0.05) during the OKG+ period. Variations of IGF1 concentrations correlated with HV variations (r = 0.82, P < 0.005) during both periods. This study demonstrates that OKG is associated with statural growth acceleration and increased IGF1 concentrations.

Adolescent↗
PubMed1994

Can arginine and ornithine support gut functions?

Arginine and ornithine are precursors of nitric oxide and polyamines, respectively. These metabolites intimately participate in permeability and adaptive responses of the gut. The liver possesses high arginase activity as an intrinsic part of urea synthesis and would consume most of the portal supply of dietary arginine. The gut reduces this possibility by converting dietary arginine to citrulline, which effectively bypass the liver and is resynthesized to arginine in the kidney. Dietary ornithine supplementation, in the form of ornithine alpha-ketoglutarate (OKG) can be considered as an arginine precursor. Several supplement studies have shown both amino acids to promote growth hormone and insulin secretion with anabolic effects in postoperative patients. Their intermediary metabolites (for example, glutamine, proline) may also be of benefit in trauma metabolism. Specific effects of either amino acid on the gut are poorly reported. One recent animal study showed improved morphology after OKG administration, perhaps through increased polyamine secretion. Generation of nitric oxide from arginine has two facets. Excess production from high dose arginine potentiated the effects of experimentally induced sepsis, whereas low doses improved survival. These considerations suggest that the role of enteral diet supplementation with arginine or OKG should be urgently examined for any benefits it may have on mucosal barrier function.

Arginine↗
PubMed1994

Assessment of the carbon tetrachloride-induced cirrhosis model for studies of nitrogen metabolism in chronic liver disease.

We evaluated the rat cirrhosis model obtained by repeated intraperitoneal administration of CCl4 (group C) with regard to biological and nutritional conditions in comparison to ad libitum (group AL) and pair-fed control rats. Cirrhotic rats were divided into two groups according to their clinical condition: group C1 (n = 4) represented those in good physical condition and group C2 those (n = 10) in poor physical condition. Autopsy indicated that rats in group C2 suffered from severe malnutrition as judged by body weight, carcass weight and the carcass/body weight ratio. However, all 14 treated rats presented the same micronodular cirrhosis and the same alterations in liver function, except for alkaline phosphatase activity (group C1: 110 +/- 63 IU/l, group C2: 259 +/- 110 IU/l; p < 0.05). In the cirrhosis groups, plasma levels of branched-chain amino acids (BCAA) and the BCAA/aromatic amino acid (AAA) ratio were significantly reduced, but values in groups C1 and C2 were not significantly different (BCAA/AAA: 1.9 +/- 0.9 in group C1, 1.5 +/- 0.8 in group C2, 2.8 +/- 0.3 in group AL; C1 and C2, vs. AL: p < 0.05). These alterations were similar to those observed in human cirrhosis and were not solely the result of reduced food intake, as indicated by the lack of difference between pair-fed and ad libitum-fed control rats.

Amino Acids↗
PubMed1993

[Enteral nutrition in patients with chronic obstructive bronchopathy treated by artificial ventilation. Effect of conventional feeding on anthropometric and biochemical parameters].

The influence of conventional gastric tube feeding on anthropometric and biochemical parameters was studied prospectively during 12 months in 14 patients with chronic obstructive lung disease put on mechanical ventilation for respiratory failure. The anthropometric parameters were: body weight, tricipital skin fold, brachial and brachial muscle circumferences. The biochemical parameters included albumin, transferrin, retinol binding protein, transthyretin, acid alpha-1-glycoprotein, C-reactive protein, fibronectin and amino acids in blood, and 3-methylhistidine in urine. Measurements were performed on inclusion, then every 3 days until D15. After 15 days of a nutrition bringing 28.8 +/- 8.9 calories/kg/day and 13.9 +/- 2.2 grams of nitrogen per day, no improvement in anthropometric parameters was observed. On D0, comparisons with healthy controls showed that visceral serum proteins levels were significantly lower and inflammatory proteins levels significantly higher (P < 0.05); the levels of protein metabolism markers were higher, but not significantly, and those of the principal glucose-forming amino acids were significantly lower (P < 0.01). On D15, comparisons with the initial values showed that the values of retinol binding protein and transthyretin were increased (P < 0.05 and 0.01 respectively), whereas the values of the other visceral proteins were little modified; yet their concentrations remained significantly lower than those found in controls, except for the retinol binding protein. Inflammatory proteins levels were high, with a significant (P = 0.05) difference for the acid alpha-1-glycoprotein, and the patients remained in slight catabolism while their nitrogen balance was positive. These results should encourage to carry out studies on the qualitative composition of artificial nutrition in order to optimize its effectiveness in the treatment of these patients.

Aged↗
PubMed1992

IL-1 beta, a strong mediator for glucose uptake by rheumatoid and non-rheumatoid cultured human synoviocytes.

Higher basal 2-deoxy-D-glucose uptake in rheumatoid synovial cells than in non-rheumatoid synovial cells, was found to be associated with an increased interleukin-1 beta (IL-1 beta) secretion (respectively 850 +/- 238 vs. 8.3 +/- 2.4 pg/24 h/10(5) cells, mean +/- S.E.M.). When exogenous human recombinant IL-1 beta was added to cultures, a marked stimulation of 2-deoxy-D-glucose uptake was performed by both human synovial cultured cells, in a time-dependent and dose-dependent manner (IL-1 beta 0-100 ng/ml). In non-rheumatoid synoviocytes, stimulation occurred 1-3 h following the addition of 1 ng/ml interleukin-1 beta and increased up to 24 hours (respectively +150% and +261.4% after 6 and 24 hours association time). Rheumatoid synovial cells were less sensitive to 1 ng/ml IL-1 beta (respectively +80% and +146.4%). IL-1 beta increased significantly the Vmax for 2-deoxy-D-glucose uptake by synovial cells, with no change in the Km. This effect was protein synthesis-dependent, and not secondary to prostaglandin E2 synthesis or cell growth. IL-1 beta possesses an important effect on glucose homeostasis in synovial cells, which could be indirect and/or regulated by the presence of natural inhibitors.

Arthritis, Rheumatoid↗
PubMed1992

Intrasplenic hepatocellular transplantation corrects hepatic encephalopathy in portacaval-shunted rats.

The aim of this work was to evaluate the effect of intrasplenic hepatocellular transplantation on hepatic encephalopathy in an experimental model of chronic liver failure induced by end-to-side portacaval shunt in the rat. Inbred male Wistar Furth rats were divided into three groups: rats subjected to portacaval shunt (n = 10), rats subjected to portacaval shunt and intrasplenic hepatocellular transplantation of 10(7) hepatocytes isolated from livers of syngeneic rats (n = 10) and sham-operated rats (n = 10). Behavior tests were performed in a blind fashion at 3 wk, at 2 mo and at 3 mo after surgery. Spontaneous activity and nose-poke exploration by individual rats were studied in automated open field boxes equipped with infrared cells. Each cell beam interruption was automatically recorded on a microcomputer and transformed into a score index (counts/hour). Plasma levels of amino acids, ammonia and total biliary acids were measured. Portacaval shunt rats showed reduced spontaneous activity and nose-poke exploration scores. Intrasplenic hepatocellular transplantation significantly increased spontaneous activity after 2 mo and improved nose-poke exploration after 3 wk. At 3 mo, spontaneous activity and nose-poke exploration in portacaval shunt/intrasplenic hepatocellular transplantation rats were not significantly different from those of sham rats. Increases in plasma ammonia levels after portacaval shunt were not corrected. Amino acid imbalance and bile acid concentration in plasma were partially corrected by intrasplenic hepatocellular transplantation. These data show that intrasplenic hepatocellular transplantation can correct the neurological symptoms of hepatic encephalopathy in an experimental model of chronic liver failure and suggest that intrasplenic hepatocellular transplantation might be of therapeutic interest in chronic liver failure.

Animals↗
PubMed1992

Branched-chain amino acid metabolism in isolated perfused liver of cirrhotic rats.

We examined the possible contribution of the liver to the alterations in branched-chain amino acid (BCAA) metabolism in cirrhosis. The livers of male Sprague-Dawley rats with CCl4-induced cirrhosis were removed and placed in a recirculating perfusion system. Net amino acid uptake and release were determined over 55 min. Results were compared with those obtained with control animals, which were either pair-fed or fed ad libitum. Intrahepatic amino acid concentrations were determined at the end of the perfusion. The release of isoleucine and leucine was significantly lower in the cirrhotic livers than in the controls fed ad libitum. There was no difference between the cirrhotic and pair-fed groups with regard to the fluxes of the three BCAA. Intrahepatic concentrations of BCAA were reduced only in pair-fed controls. These results suggest that both cirrhosis and a low protein/calorie diet alter hepatic BCAA flux, but via different mechanisms. In cirrhosis, alterations could be due both to low food intake and to BCAA metabolism in non-parenchymal cells.

Amino Acids, Branched-Chain↗
PubMed1992

[Effects of fatty acids on hepatic amino acid metabolism in isolated perfused liver in rats].

Large disparity in experimental conditions concerning the use of isolated perfused liver led us to investigate the effects of two free-fatty acids on amino acid metabolism in this model. Oleate uptake was 210 +/- 46 nmol/min.g and octanoate uptake 550 +/- 60 nmol/min.g. Fatty acid utilization led to an increase in ketogenesis, enhanced by octanoate in accordance with its known availability for beta-oxidation. In our experiments neither oleate nor octanoate modified hepatic amino acid exchange and metabolism as assessed by the measurements of amino acids fluxes and glucose and urea production.

Amino Acids↗
PubMed1991

Methods and limitations of an experimental model of long QT syndrome.

An experimental model of the long QT syndrome has been developed in conscious dogs. This report discusses the methods used in its preparation and the strengths and weaknesses of the model. This new model is suitable for screening the bradycardia-dependent proarrhythmic effects of drugs and for studying the electrophysiology of "torsades de pointes." Permanent bradycardia (RR: 1558 +/- 83 ms) was obtained in 37 dogs by chemically-induced complete atrioventricular block. A 10% further increase of ventricular repolarization (QT: 306 +/- 7.0 ms to 331 +/- 5.5 ms) was obtained in 28 of these dogs by diuretic-induced hypokalemia. Diuretics, despite saline replacement, induced some degree of functional renal failure and extracellular volume losses. The QT interval increased although ventricular cycle length decreased slightly. These biological and electrophysiological parameters were reproducible except for a slow increase in plasma creatinine. Cardiac failure and sudden death rarely occurred. The most severe, but reversible, renal failure occurred in some dogs given the highest diuretic doses. Hypokalemia resulted in ventricular arrhythmias in only 6 dogs, 2 of them exhibiting runs of ventricular tachycardia and even "torsade de pointes" as their potassium levels fell below 2 mmol/L. The results of studies with several drugs using the model, with or without hypokalemia, or with bradycardia worsened by propranolol are analysed.

Animals↗