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L Cynober

Publications and source records attributed to L Cynober.

At least 73 records · Page 4Linked to original sources
PubMed1997

Ornithine alpha-ketoglutarate metabolism after enteral administration in burn patients: bolus compared with continuous infusion.

Ornithine alpha-ketoglutarate (OKG) has been successfully used as an enteral supplement in the treatment of catabolic states, including burn injury. However, specific questions remain unanswered concerning burn patients, including OKG metabolism and metabolite production, appropriate mode of administration, and dose. We thus performed a kinetic study and followed plasma ornithine and OKG metabolite concentrations on day 7 postburn in 42 (35 men, 7 women) consecutive burn patients aged 33 +/- 2 y with a mean (+/-SEM) total burn surface area (TBSA) of 31 +/- 1%. Patients were randomly assigned to receive OKG as a single bolus (10 g; n = 13) or in the form of a continuous gastric infusion (10, 20, or 30 g/d over 21 h; n = 13) or an isonitrogenous control (n = 16). Plasma pharmacokinetics of ornithine followed a one-compartment model with first-order input (r = 0.993, P < 0.005). OKG was extensively metabolized in these patients (absorption constant = 0.028 min-1, elimination half-life = 89 min), with the production of glutamine, arginine, and proline; proline was quantitatively the main metabolite [in OKG bolus, area under the curve (AUC)0-7h: proline, 41.4 +/- 5.6 mmol.min/L; glutamine, 20.4 +/- 5.7 mmol.min/L; and arginine, 7.3 +/- 1.9 mmol.min/L]. Proline production was dose-dependent and quantitatively similar between modes of OKG administration. Glutamine and arginine production were not dose-dependent and were higher in the bolus group than in the infusion group. Overall, the bolus mode of OKG administration appeared to be associated with higher metabolite production compared with continuous infusion in burn patients, especially for glutamine and arginine.

Adult↗
PubMed1997

Ornithine alpha-ketoglutarate modulates tissue protein metabolism in burn-injured rats.

Enterally administered ornithine alpha-ketoglutarate (OKG) displays whole body anabolic and anticatabolic properties in trauma situations, especially after burn injury. The aim of this study was to get information about the anabolic effect of OKG at tissue level. Thirty-six male Wistar rats (95 +/- 7 g) were allocated to four groups. Eighteen rats were burned by water (20% body surface area). After a 24-h fast (day 0-day 1), rats were enterally refed for 48 h (day 1-day 3) by use of Osmolite as a low-calorie, low-nitrogen regimen supplemented with either 5 g OKG.kg-1.day-1 (B-OKG) or an equivalent amount of nitrogen in the form of glycine (B-Gly). Nonburned pair-fed controls treated with glycine (C-Gly) and healthy rats fed ad libitum were also studied. On day 3, protein synthesis rates (large dose method), free glutamine concentrations, and total protein content were assessed in tissues. Myofibrillar degradation was assessed by measuring urinary 3-methylhistidine excretion daily from day 0 to day 3. With regard to tissue protein synthesis rates, we demonstrate for the first time that OKG displays anabolic properties in the jejunum [fractional synthesis rate (FSR) in %/day, ad libitum = 101.9 +/- 4.0; C-Gly = 84.7 +/- 3.1, P < 0.01 vs. ad libitum; B-Gly = 84.5 +/- 1.6, P < 0.01 vs. ad libitum; B-OKG = 97.5 +/- 3.2, P < 0.05 vs. C-Gly and B-Gly] as well as in the liver (FSR in %/day, ad libitum = 75.9 +/- 3.7; C-Gly = 53.2 +/- 3.8, P < 0.01 vs. ad libitum; B-Gly = 70.2 +/- 2.0, P < 0.01 vs. C-Gly; B-OKG = 98.7 +/- 4.6, P < 0.01 vs. ad libitum, C-Gly and B-Gly), the latter having previously been observed in vitro. Furthermore, we confirm that OKG inhibits myofibrillar degradation, counteracts the trauma-induced fall of muscle glutamine pool, and induces an increase in glutamine concentration in the jejunum.

Animals↗
PubMed1997

Amino acid determination in biological fluids by automated ion-exchange chromatography: performance of Hitachi L-8500A.

The Hitachi L-8500A is a newly available apparatus for amino acid (AA) analysis that allows automatic on-line mixing of the ninhydrin reagent. The within-run precision (human plasma pools at three different concentrations) showed CVs < 3.8% except for the lowest concentration of citrulline (4.4%), Tyr (4.5%), and alpha-aminobutyric acid (7.6%), and for the intermediate concentration of Asp (8.7%). Between-run precision (CV) was < 3.1% for 17 AAs and < 8.0% for 24 of 25 AAs (CV Asp = 12.0%). For retention times, within-run precision was < 0.4% and between-run precision < 1.8%. Excellent relations were found between the results from the Hitachi L-8500A and the widely used Beckman 6300 analyzer (0.929 < or = r < or = 0.999). The detection was still linear at 5 mumol/L except for Pro and hydroxyproline (20 mumol/L). The upper limit was at least 2500 mumol/L for 13 AAs and at least 1000 mumol/L for 27 of 29 AAs (anserine = 500, Val = 600 mumol/L). Values from 100 human plasma samples agreed with previously published data. We conclude that the results obtained with the Hitachi L-8500A are satisfactory when compared with those of other AA analyzers utilizing the same method. Furthermore, the Hitachi L-8500A displays several advantages including programming flexibility, microsample capacity, low noise plotting, ammonia filtering, and manual repacking of the analytical column.

Amino Acids↗
PubMed1996

Kinetic nephelometric determination of albumin produced by rat hepatocytes in culture.

A kinetic immunonephelometric method for the determination of albumin produced by rat hepatocytes in culture is described. This assay is simple, rapid and sensitive. The methodology allows detection of 0.7 mg/l albumin in 200 microliters of culture medium. Within-run precision CVs for three levels of concentrations were under 1.0% and between-day precision CVs were under 4.1%. The range of measurement obtained using appropriately diluted samples was 1.2 to 74 mg/l. The rabbit IgG fraction to rat albumin used in this method did not cross-react with albumin from cow, allowing the use of fetal calf serum in the medium. The method described can thus be used easily for the assessment of albumin synthesis in cellular studies using isolated hepatocytes.

Albumins↗
PubMed1996

Immunomodulatory effects of ornithine alpha-ketoglutarate in rats with burn injuries.

OBJECTIVE: To investigate the influence of enterally administered ornithine alpha-ketoglutarate (OKG) on muscular amino acid content, eicosanoid release, and polymorphonuclear leukocyte responsiveness after induction of burn injury in rats. DESIGN: Experimental trial. MATERIALS AND METHODS: Four groups of rats were considered: (1) healthy rats that received a standard diet supplemented with 5 g/kg per day of OKG; (2) rats with burn injuries that received the same nutrition as group 1; (3) healthy rats that received standard diet supplemented with glycine in an isonitrogenous amount relative to OKG; and (4) rats with burn injuries that received the same nutrition as group 3. The thymus and 1 skeletal muscle were weighed. The oxidative metabolism of pleural polymorphonuclear leukocytes was measured by means of superoxide generation (O2-) and the chemiluminescent response to opsonized zymosan. Prostaglandin E2 and 6-keto-prostaglandin F1 alpha were measured in the supernatants of pleural and peritoneal cells. RESULTS: The weights of the thymus and the muscle from healthy rats were similar. Those of rats from group 4 were significantly lower (P < .05), whereas those of rats from group 2 were not. Metabolism of OKG led to enhanced amounts of arginine and glutamine in skeletal muscle. The metabolic bursts of polymorphonuclear leukocytes from healthy rats were similar. Those of glycine-treated rats with burn injuries were significantly depressed (P < .05), whereas those of the OKG-treated group were not. Pleural and peritoneal cells from the rats with burn injuries that received OKG generated significantly more prostaglandins (P < .01) than did cells from the other groups of rats. CONCLUSION: Ornithine alpha-ketoglutarate administered to rats with burn injuries displays immunomodulatory properties that can enhance host-defense mechanisms in animals that are affected by a severe injury.

Animals↗
PubMed1996

alpha-Ketoglutarate uptake in human fibroblasts.

Glutamine requirements are increased during injury, in particular to sustain the needs of rapidly growing cells. This includes fibroblasts involved in wound healing. alpha-Ketoglutarate (alpha-KG) has been proved to be a potent precursor of glutamine. However, little is known about the process of its cell uptake. Since this first step could be crucial in alpha-KG metabolism, we have characterized alpha-ketoglutarate uptake in fibroblasts. Total uptake of alpha-ketoglutarate was linear up to 1 mmol and temperature independent. Rate of uptake was independent of the presence of Na+ in the medium. Competition studies with another ketoacid demonstrated the nonspecificity of alpha-ketoglutarate uptake. In addition, 4-hydroxy-alpha-cyanocinnamate, a known inhibitor of anion transport, was ineffective on alpha-ketoglutarate uptake. Taken as a whole, these data provide evidence that alpha-ketoglutarate uptake in fibroblast occurs by an unmediated diffusion process. This suggests that alpha-ketoglutarate uptake is not the controlling step in fibroblasts, i.e. only the availability of extracellular alpha-ketoglutarate. This could be an advantage since during injury, cell membrane depolarization and dissipation of Na+ gradient may limit cellular glutamine uptake.

Amniotic Fluid↗
PubMed1996

Protein metabolism in cachectic tumor-bearing rats: effect of tumor excision.

The effect of tumor resection on protein metabolism in cancer-bearing subjects is poorly documented. We explored changes in nitrogen (N) and protein metabolism after excision of tumors both at the whole body level (N balance) and at the tissue level, including skeletal muscle, small intestine, and liver. Sixteen male Sprague-Dawley rats (approximately 375 g) bearing subcutaneous Morris hepatoma 7777 for 6 weeks were either operated for tumor excision and studied for 10 days postoperatively (n = 10) or sacrificed on the day of surgery as tumor-bearing controls; operated and unoperated tumor-bearing rats were compared with healthy rats (n = 16). Tumors, which grew to a mass of 74 +/- 7 g (mean +/- SEM), induced significant loss of body mass (-27 +/- 13 g) and protein depletion in epitrochlearis muscle (EPI) (-38%) and small intestine (-42%) vs healthy rats. Tumor significantly decreased muscle protein synthesis vs healthy rats (7.14 +/- 0.5 vs 10.7 +/- 0.5 nmol phenylalanine (Phe)/EPI/3 hr), net degradation (21.7 +/- 2.9 vs 30.6 +/- 2.5 nmol Phe/EPI/3 hr) and degradation (28.8 +/- 2.7 vs 41.4 +/- 2.5 nmol Phe/EPI/3 hr). In 50% of operated rats, tumor removal was followed immediately by increased food intake, body weight, and N balance; in other rats, this was delayed by 2-4 days. By 6 days postoperative, all rats were gaining weight and had normal food intake; wasting was abolished in small intestine, but not in skeletal muscle (protein mass -43% vs healthy rats, P < 0.05). Postoperative rats maintained lower muscle protein degradation (28.2 +/- 2.0 vs 41.4 +/- 2.5 nmol Phe/EPI/3 hr, P < 0.05) than healthy rats; protein synthesis was no longer reduced. In skeletal muscle, protein synthesis and protein deposition were related to levels of postoperative food intake (r = 0.91 and 0.98, respectively; P < 0.05). Following tumor excision, reversal of cancer cachexia appeared to be highly dependent on the level of postoperative food intake.

Animals↗
PubMed1996

Glutamine metabolism and neuropathological disorders in experimental hepatic encephalopathy: effect of transplanted hepatocytes.

BACKGROUND: Physiopathology of hepatic encephalopathy remains unclear. Recent studies have suggested that ammonia would not act by itself but through an increase in glutamine in the brain. We have previously demonstrated that transplantation of syngeneic hepatocytes into the spleen was able to correct both behavioral deficits and plasma amino acid changes observed in portacaval shunted rats. The aim of the present work was to show a correlation between the correction of chronic hepatic encephalopathy by means of intrasplenic hepatocyte transplantation and two parameters, brain glutamine concentration and ultrastructural aspects of astrocytes. METHODS: Inbred male Wistar Furth rats were divided into three groups: sham-operated rats (n = 10), rats subjected to portacaval shunt (n = 10), and rats subjected to portacaval shunt and intrasplenic hepatocellular transplantation of 10(7) hepatocytes isolated from livers of syngeneic rats (n = 10). Chronic hepatic encephalopathy was quantified 30 and 60 days after operation by means of nose-poke exploration and spontaneous activity. Pathologic examination and measurement of glutamine concentrations in the corpus striatus and in the cerebral cortex were performed 60 days after operation. RESULTS: Portacaval shunt rats showed reduced spontaneous activity and nose-poke exploration scores. After portacaval shunt a significant glutamine increase occurred in the corpus striatus and in the cerebral cortex when compared with sham rats (p < 0.05). Ultrastructural examination showed modification of astrocytes named Alzheimer type II after portacaval shunt. Correction of behavioral abnormalities by means of intrasplenic hepatocyte transplantation was associated with partial correction of striatal glutamine increase and with decrease in astrocyte alterations. Cortex glutamine concentration in portacaval shunt-intrasplenic hepatocyte transplantation group and in portacaval shunt rats did not differ significantly. CONCLUSIONS: These data show that intrasplenic hepatocyte transplantation not only prevents neurologic disorders of hepatic encephalopathy but can also decrease glutamine and ultrastructural alterations in the corpus striatus in an experimental model of chronic liver failure. These data are in favor of the involvement of glutamine in chronic hepatic encephalopathy. These results suggest that intrasplenic hepatocyte transplantation might be of therapeutic interest in chronic liver failure.

Animals↗
PubMed1996

Ornithine alpha-ketoglutarate counteracts thymus involution and glutamine depletion in endotoxemic rats.

This work studied the action of ornithine a-ketoglutarate (OKG) supplementation in an experimental model of endotoxemia in the rat. Male Wistar rats were injected intraperitoneally with lipopolysaccharide (LPS) from Escherichia coli (0127:B8). They were fasted for 24 h, then refed for 48 h with an enteral diet supplemented with either OKG (66 mg N x kg(-1) x d(-1)) or glycine, isonitrogenous to the OKG group. A control (sham) group was also studied. LPS treatment induced a decrease in thymus and muscle weights compared to controls, and a decrease in glutamine and arginine concentrations in the anterior tibialis muscle. Supplementation with OKG restored thymus weight and muscle arginine level and increased muscle glutamine concentration, when compared to controls. We conclude that OKG counteracts the thymic involution that occurs with endotoxemia, and restores the muscular content of glutamine and arginine, both of which are involved in the regulation of immune function.

Journal Article↗
PubMed1996

Supplementation of oral nutrition with pancreatic enzymes improves the nutritional status of aged endotoxemic rats.

Malnutrition is a common problem in elderly people. The association of malnutrition and physical illness or injury leads to both localized and general complications. In particular, impairment of the adaptive response of pancreatic function to undernutrition and refeeding may adversely affect nutritional status and elicit morbidity and mortality. Aged rats (24 mo old) were treated with lipopolysaccharide (LPS) from E. Coli (3 mg/kg body weight). Six days later, survivors were randomized to receive, for 7 days, an oral chow diet enriched with either a pancreatic extract (PE) (2.4 mg/day) or an isonitrogenous supply of casein (CAS). Endotoxemia induced a catabolic state, with a body weight loss of 7.6 +/- 1.1% on day two after LPS treatment. Mean food intake from day 6 to day 13 was similar in LPS-PE and LPS-CAS groups (19.0 +/- 5.6 versus 19.7 +/- 6.9 g). The metabolic response varied according to the type of muscle studied. In fast (white) muscle, the protein content and the glutamine pool remained markedly depleted in endotoxemic rats receiving casein supplementation. In contrast, enrichment of nutrition with PE significantly limited the LPS-induced muscle wasting and increased the muscle glutamine content. As in previous observations, no significant change occurred in slow (red) muscle. These results could indicate that PE supplementation counteracts pancreatic deficiency caused by aging and worsened by stress and this, in turn, could improve the efficiency of nutrition, to support the hypermetabolism of aged injured rats.

Aging↗
PubMed1995

No evidence for a tumor necrosis factor alpha stimulated 2-methylaminoisobutyric acid uptake in hepatocyte monolayer.

This study investigates the short-term effects of glucagon and human recombinant tumor necrosis factor alpha (TNF alpha) singly and in association on 2-methylaminoisobutyric acid (MeAIB) transport in hepatocyte monolayers. As expected, glucagon induced a time-dependent stimulation of MeAIB transport. In our experimental conditions, TNF alpha did not induce cytolysis. A 2 hour exposure to TNF alpha (0.05-500 ng/l) with or without glucagon (10(-9) to 10(-6) M) did not modify the basal or glucagon-stimulated MeAIB transport. Varying the duration of exposure to TNF alpha 5 ng/l up to 6 h was equally ineffective. The presence of hydrocortisone potentiated the glucagon-stimulated transport, but TNF alpha remained ineffective. Finally, the association of interferon (IFN gamma) with TNF alpha and/or glucagon was unable to modify the transport activity. These data demonstrate that TNF alpha does not exert a direct effect on MeAIB transport in hepatocytes, at least on a short-term basis.

Animals↗
PubMed1995

Evidence for the detrimental role of proteolysis during liver preservation in humans.

BACKGROUND/AIMS: Proteolysis may persist in the liver allograft during cold storage. The aim of this study was to determine the significance of proteolysis within liver allografts stored at 4 degrees C in University of Wisconsin preservation fluid. METHODS: Thirty recipients of 32 liver allografts were studied prospectively. Amino acid content of the preservation fluid was analyzed at the end of cold storage and was correlated to graft and patient outcome after transplantation. RESULTS: Analysis of the preservation fluid showed the presence of free amino acids, the profile of which was different from that of stored liver parenchyma. Concentrations of amino acids (alanine, cysteine, leucine, isoleucine, methionine, lysine, ornithine, and threonine) and transaminases (alanine aminotransferase and aspartate aminotransferase) in the preservation fluid correlated with the duration of cold ischemia. Indexes of graft dysfunction (serum alanine aminotransferase and aspartate aminotransferase peaks and prothrombin rate) correlated with concentrations of cysteine, alanine, isoleucine, leucine, methionine, lysine, ornithine, and threonine, whereas enzyme concentrations in the fluid were not predictive of graft dysfunction. CONCLUSIONS: These data suggest that liver proteolysis occurs during cold storage and may have a detrimental effect on the outcome after transplantation. The measurement of the amino acids in the preservation fluid at the end of the cold storage period could help to identify the most severely damaged organs.

Adenosine↗
PubMed1995

Negative impact of cancer chemotherapy on protein metabolism in healthy and tumor-bearing rats.

Although chemotherapeutic agents are widely used in the treatment of cancer, few experimental data are available on their effects on host N metabolism. We studied the effects of a single intraperitoneal (IP) injection of cyclophosphamide ([CYP] 120 mg/kg), 5-fluorouracil ([5-FU], 50 mg/kg), cisplatinum ([CDDP], 5 mg/kg), or methotrexate ([MTX], 30 mg/kg). N balance was studied for 6 days following chemotherapy in healthy rats (n = 40) and in rats bearing Morris Hepatoma 7777 ([MH7777] n = 40) in a situation comparable to that of human cancer (tumor burden < 0.2% of body weight, moderate anorexia, and weight loss). In healthy rats, all drugs induced transient body weight loss, anorexia, and poor N balance. At day 6 posttreatment, all animals had resumed normal feed intake and positive N balance except CDDP-treated rats, which showed continued weight loss and poor N balance. CDDP and MTX exhibited antitumor activity; however, CDDP induced diarrhea in six of eight tumor-bearing rats. Drug-induced anorexia was more severe in tumor-bearing than in healthy treated rats. N balance was more severely decreased in MH7777-bearing rats than in healthy treated animals in response to 5-FU (159 +/- 36 v 273 +/- 27 mg N/2 d) and MTX (-66 +/- 36 v 153 +/- 37 mg N/2 d) at days 3 to 4 postinjection. These results establish the presence of drug-specific effects on host N balance and the existence of a drug-tumor interaction for N metabolism in the tumor-bearing host.

Animals↗
PubMed1995

[Role of new nitrogen substrates during peri-operative artificial nutrition in adults].

Some amino acids and their derivatives, such as arginine (ARG), glutamine (GLN) in free form or as dipeptides, and ornithine-ketoglutarate (OKG), have specific pharmacological properties concerning namely immunomodulation, control of protein turn-over, maintenance of gut trophicity. In the context of the postoperative nutrition in the adult, supplementation of enteral nutrition with ARG and of parental nutrition with GLN and OKG has improved nutritional and biochemical markers such as nitrogen balance, muscle protein synthesis and glutamine content. However, only few studies have tried to demonstrate a clinical benefit with such a supplementation. At present only the beneficial effect of OKG on postoperative wound healing has been recognized.

Adult↗
PubMed1995

Metabolism of ornithine, alpha-ketoglutarate and arginine in isolated perfused rat liver.

Ornithine (Orn; alpha-ketoglutarate (alpha KG) salt) and arginine (Arg) supplementation of enteral diets has been advocated in the treatment of hypercatabolism of trauma patients, but both compounds are subject to extensive hepatic metabolism. To compare the metabolism of these two compounds and to evaluate the possible influence of the alpha KG moiety, livers were perfused with alpha KG, Orn, ornithine alpha-ketoglutarate (OKG) or Arg (n 6 in each group) for 1 h. Arg uptake was nearly fourfold higher than Orn uptake (690 (SD 162) v. 178 (SD 30) nmol/min per g liver), and Orn uptake was not modified by alpha KG. Orn was totally metabolized by the liver, whereas Arg led to Orn release (408 (SD 159) nmol/min per g liver) and a threefold stimulation of urea production (Arg 1.44 (SD 0.22) v. Orn 0.45 (SD 0.09) mumol/min per g liver). alpha KG alone only increased hepatic aspartate uptake but, when associated with Orn as OKG, it led to an increase in glutamate release and in proline content in the liver and to a decrease in proline uptake. From these findings we conclude that (1) Arg load is extensively metabolized by the liver, inducing urea production, (2) in enteral use, Orn supplementation appears preferable to Arg as it is less ureogenic (as also recently demonstrated in vivo in stressed rats receiving isomolar amounts of Arg and Orn), (3) the liver participates in the Orn-alpha KG metabolic interaction, mostly in proline metabolism, which occurs in the splanchnic area.

Animals↗
PubMed1995

Supplemental nutrition with ornithine alpha-ketoglutarate in rats with cancer-associated cachexia: surgical treatment of the tumor improves efficacy of nutritional support.

We investigated the use of ornithine alpha-ketoglutarate in treatment of rats bearing Morris hepatoma 7777. Rats received diets containing either ornithine alpha-ketoglutarate, which has been used in other catabolic states (i.e. injury, sepsis), or an isonitrogenous, isocaloric diet containing glycine. Untreated tumors grew to a mass of 11 g/100 g body weight over the 3-wk period after implantation and induced progressive anorexia, negative nitrogen balance, and body and tissue wasting. Compared with glycine, ornithine alpha-ketoglutarate had no effect on tumor growth, but also did not alter the catabolic effects of the tumor on its host. We hypothesized that capture of amino acids by the tumor limited the efficacy of supplemental nutrition here and in published reports in which tumor burden comprised 4-30% of body weight. This is supported by our observation that a 3-wk of implantation the rate of protein deposition plus amino acid oxidation by the tumor was equivalent to approximately 70% of the host's daily protein intake. To parallel the clinical situation in which tumor burden is small at diagnosis and initiation of treatment, the same diets were tested in rats treated by excision of the tumor at a limited stage of the disease. Rats received 3 d preoperative nutrition with ornithine alpha-ketoglutarate or glycine, and continued on the same diets for 3 or 6 d postoperatively. Compared with glycine-fed rats, ornithine alpha-ketoglutarate-fed rats showed a more positive nitrogen balance, higher concentrations of glutamine and branched-chain amino acids in muscle, and accelerated protein deposition in small intestine (P < 0.05). Our results explain the lack of success of nutritional support in untreated cancer and underline the need for clinically relevant animal models for further studies.

Amino Acids↗