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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The plasma concentrations of substrates, together with transhepatic and transgut balances, have been studied in six control and eight septic awake fasted dogs. Four severely ill septic dogs (typically fluid in chest and/or abdomen, extensive peritonitis, respiratory difficulties) had high concentrations of threonine, glycine, tyrosine, lysine, histidine, tryptophan, and triglycerides (p less than or equal to 0.05). The other septic dogs (less severely ill) showed fewer and less pronounced alterations in the plasma substrates (aspartate and tryptophan were elevated, p less than or equal to 0.05). The infusion of glucose increased the concentration of glucose, lactate, and pyruvate and depressed the concentrations of most amino acids in both normal and septic dogs. Threonine, asparagine, glutamine, leucine, isoleucine, alpha-aminobutyrate, and tyrosine were significantly depressed in the severely ill septic dogs (p less than or equal to 0.05). In the normal dogs most amino acids were removed by the liver, with alanine accounting for approximately 40% of the total. Glutamine removal was negligible. In the septic dogs hepatic removal of amino acids was variable; livers of two severely ill septic dogs did not remove amino acids. In the control dogs glucose infusion (0.015--0.017 g/kg/min) tended to lower hepatic removal of amino acids. Hepatic dye removal in the septic dogs was always very poor. In the gut glutamine was removed and alanine, glutamate, glycine, and ammonia produced, but the overall sum of amino acid uptake was negligible in both the control and septic dogs. The ratio of tryptophan to the sum of valine, isoleucine, leucine, tyrosine, and phenylalanine concentrations was greatly elevated in all septic dogs in which it was measured. The free concentrations of amino acids in the liver, heart, and muscle tissues were grossly elevated in the low intravenous alimented septic state relative to the fasted normal state, whereas the tissue concentrative ability as measured by nonmetabolizable amino acids, alpha-aminoisobutyrate and cycloleucine, was not similarly increased. Sepsis clearly alters plasma and tissue concentrations, and in some instances hepatic uptake of amino acids.
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PMID:Plasma concentrations and tissue uptake of free amino acids in dogs in sepsis and starvation: effects of glucose infusion--some effects of low alimentation. 65 52

1. The effects of parenteral nutrition with or without glutamine supplementation and epidermal growth factor treatment (0.15 microgram/g body weight) was studied in the small bowel of septic rats after 4 days. 2. Septic rats infused with glutamine-supplemented parenteral nutrition with or without epidermal growth factor treatment survived sepsis significantly better than other septic rats given parenteral nutrition. The cumulative percentage of deaths over 4 days in septic rats infused with glutamine-supplemented parenteral nutrition was 20% (without epidermal growth factor) and 15% (with epidermal growth factor) compared with 50% in septic rats treated with parenteral nutrition without glutamine and 35% in septic rats given parenteral nutrition without glutamine but with epidermal growth factor treatment. 3. Glutamine-supplemented parenteral nutrition with or without epidermal growth factor treatment resulted in improved nitrogen balance in septic rats. The cumulative nitrogen balance over the 4 day period was the least negative as compared with other groups of septic rats. 4. Septic rats given parenteral nutrition with glutamine, epidermal growth factor or glutamine and epidermal growth factor exhibited marked increases in intestinal net rates of utilization of glutamine (P less than 0.001) and production of ammonia (P less than 0.001) compared with septic rats given parenteral nutrition without glutamine and/or epidermal growth factor treatment. 5. Septic rats given parenteral nutrition with glutamine, epidermal growth factor or glutamine and epidermal growth factor exhibited significant increases in jejunal wet weight (by 32.4-40.6%), DNA content (by 24.2-34.7%), protein content (by 29.1-50.0%), villus height (by 16.3-26.4%) and crypt depth (by 20.3-29.6%) compared with other groups of septic rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of epidermal growth factor and glutamine-supplemented parenteral nutrition on the small bowel of septic rats. 131 68

The effect of the combination of total parenteral nutrition (TPN) and systemic sepsis on mucosal morphology and protein synthesis was investigated. Rats were given a standard TPN mixture consisting of glucose (216 kcal.kg-1.day-1), lipid (24 kcal.kg-1.day-1), and amino acids (1.5 g N.kg-1.day-1) for 5 days. On the 5th day the rats (n = 37) were randomized into four groups according to diet as follows: 1) control nonseptic on standard TPN, 2) control nonseptic on TPN with glutamine, 3) septic on standard TPN, and 4) septic with the TPN supplemented with glutamine. Twenty hours after the injection of Escherichia coli, the rats were given a 4-h constant infusion of [U-14C]leucine to determine the mucosal fractional protein synthesis rates. The following results were obtained. 1) Histological examination showed that systemic sepsis caused tissue damage to the ileum and jejunum. 2) Glutamine supplementation attenuated these changes. 3) There were no visible changes to the colon either from glutamine supplementation or sepsis. 4) Sepsis was associated with an increase in mucosal protein synthesis and decreased muscle synthesis. 5) Addition of glutamine to the TPN mix further increased protein synthesis in the intestinal mucosa of septic rats.
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PMID:Effect of total parenteral nutrition, systemic sepsis, and glutamine on gut mucosa in rats. 151 20

1. The effect of total parenteral nutrition with or without glutamine enrichment was studied in septic rats after 4 days of treatment. 2. Septic rats treated with glutamine-enriched total parenteral nutrition survived sepsis significantly better than other TPN-treated septic rats: the cumulative percentage of deaths over 4 days in septic rats treated with glutamine-enriched total parenteral nutrition was 25% compared with 55% in septic rats given total parenteral nutrition without glutamine and 70% in septic rats given glucose. 3. Glutamine-enriched total parenteral nutrition resulted in improved nitrogen balance in septic rats: the cumulative nitrogen balance over the 4 days of treatment was the least negative as compared with other groups of septic rats. 4. The rate of loss of intracellular glutamine in skeletal muscle was markedly decreased (P less than 0.001) in response to glutamine-enriched total parenteral nutrition in septic rats. 5. The rate of protein synthesis was increased (21.2%) and the rate of protein degradation was decreased (35.5%) in response to glutamine-enriched total parenteral nutrition in septic rats. 6. It is concluded that the administration of glutamine-enriched total parenteral nutrition is beneficial to septic rats and possibly to septic patients.
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PMID:Effect of glutamine-enriched total parenteral nutrition on septic rats. 165 66

The hepatic toxicity of TPN that is seen clinically appears to be multifactorial in origin. Most patients develop a combination of hepatic steatosis with evidence of cholestasis and abnormalities in liver function. The model that we have studied is one of pure hepatic steatosis since, on repeated study, these rats do not develop any liver function abnormalities. It is unclear whether this is related to the fact that these are short-term experiments, that rat livers respond differently from humans, or that rats do not have gallbladders. It has not been possible to carry these experiments out beyond 3 weeks since the rats develop bacterial colonization of the central lines as well as evidence of line sepsis. thus confounding the issue of hepatic toxicity being due to the TPN or to sepsis. One hypothesis is that hepatic steatosis is an early marker of liver toxicity and that prevention or reversal of hepatic steatosis may protect the liver from further abnormality. Insulin and glucagon seem to play a critical role in the development of TPN-associated hepatic steatosis. Specifically, an elevated portal venous insulin-glucagon molar ratio appears to be the primary stimulus and any treatment that lowers this ratio should diminish hepatic steatosis. The use of glucagon as a treatment modality is new. We have found no evident side effects of low dose glucagon in rats when it is added to the TPN solution. Glutamine has received much attention recently as a nutritional pharmacological agent in ameliorating some of the intestinal complications of parenteral nutrition and is well tolerated when administered appropriately. Intravenous lipid administration is an important nonprotein calorie source, especially when a high dextrose base cannot be used, and plays a role as well in preventing the development of hepatic steatosis. Thus, it is suggested that the clinical treatment of hepatic steatosis during TPN can be safely performed using any one, or a combination, of these modalities and without having to discontinue the TPN infusions. Since we observed no deterioration of liver function in rats receiving TPN for up to 2 weeks, we cannot completely relate these findings and recommendations to the hepatic dysfunction seen clinically with the use of TPN. Additional study will be required before this can be conclusively determined.
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PMID:Pathogenesis of hepatic steatosis during total parenteral nutrition. 190 28

Glutamine and alanine are dominant nitrogen carriers from skeletal muscle stores to splanchnic organs. In addition, these amino acids may also serve as a primary energy source for the gastrointestinal tract during injury. To investigate these contributions, we studied extremity amino acid efflux during hypocaloric dextrose feedings and during total parenteral nutrition in a population of normal volunteers (NL VOL) (n = 9), a group of patients with sepsis who had undergone laparotomy without bowel resection and were in the intensive care unit (ICU) (n = 7), and patients with sepsis after laparotomy (PT) (n = 2) who had recently undergone greater than 80% bowel resection. Circulating alanine and glutamine levels were significantly lower in the patients compared with NL VOL under both feeding conditions. The peripheral output of alanine was higher in the ICU group than in the NL VOL during hypocaloric feedings. Glutamine efflux, however, was independent of either the counterregulatory hormone or substrate background. By contrast, enterectomy was associated with a marked decrease of extremity glutamine efflux compared with NL VOL or the ICU patients who did not undergo enterectomy (-62 +/- 9 nmol/min/dl tissue in the PT vs -265 +/- 32 nmol/min/dl tissue in the NL VOL and -311 +/- 58 nmol/min/dl tissue in the ICU group) during the dextrose feedings; this difference persisted during subsequent total parenteral nutrition (+12 +/- 13 nmol/min/dl tissue in PT vs -178 +/- 56 nmol/min/dl tissue in the NL VOL and -287 +/- 81 nmol/min/dl tissue in the ICU group). These data suggest that distinct mechanisms regulate peripheral alanine and glutamine balance and that the gastrointestinal tract provides a feedback signal to peripheral tissues to maintain glutamine mobilization under both nonstressed and stressed conditions.
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PMID:Influence of enterectomy on peripheral tissue glutamine efflux in critically ill patients. 196 83

To examine alterations in amino acid metabolism after trauma and sepsis, male Sprague-Dawley rats underwent no operation (control, CON), celiotomy (trauma, TRA), or cecal ligation and puncture (sepsis, CLP). After 16 hr, plasma amino acid concentrations were determined. A second group of similarly prepared animals underwent isolated liver perfusion, and net amino acid uptake or release was determined over 30 min. Sepsis significantly decreased total amino acid concentration in portal plasma (CON, 3486 +/- 156 nmole/ml; TRA, 3407 +/- 150 nmole/ml; CLP, 2738 +/- 148 nmole/ml). Glutamine concentrations were uniformly lower in portal plasma than in arterial plasma in all states. There were depressed concentrations of the branched chain amino acids (BCAA) in portal plasma after trauma but not sepsis. In the isolated liver perfusion model, a marked increase in amino acid uptake was induced by sepsis (CON, 39.9 +/- 7.9 mumol/g liver protein; TRA, 49.5 +/- 17.3 mumol/g liver protein; CLP, 124 +/- 11 mumol/g liver protein). In addition, there was significantly greater uptake of threonine, asparagine, proline, methionine, tyrosine, and arginine. Although the BCAA isoleucine and valine were taken up to a greater extent in sepsis, the overall BCAA uptake was not significantly greater in sepsis than in control (CON 6.92 +/- 2.15 mumol/g liver protein vs CLP 15.8 +/- 1.9 mumol/g liver protein). The greatest increase in uptake following sepsis was among the gluconeogenic precursor amino acids alanine, glycine, threonine, and serine (CON, 27.0 +/- 4.2 mumol/g liver protein, TRA, 38.8 +/- 8.9 mumol/g liver protein; CLP, 62.8 +/- 6.0 mumol/g liver protein).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Amino acid uptake in isolated, perfused liver: effect of trauma and sepsis. 339 92

We measured amino acid concentrations in plasma and skeletal muscle of three groups of patients with acute hemorrhagic pancreatitis: (a) patients without secondary organ lesions, (b) patients also suffering from kidney damage, and (c) patients in whom the pancreatitis was accompanied by sepsis and multiple organ failure. In all three groups, especially the third group, the amino acid concentrations in both plasma and muscle were below normal. Glutamine was only 14% of normal in muscle tissue of the third group. Onset of renal insufficiency was indicated by increasing values for 3-methylhistidine and cystathionine; multiple organ failure, by increased concentrations of methionine and phenylalanine in plasma. The low amino acid concentrations of patients with acute pancreatitis can be explained as a combined effect of semistarvation and hypercatabolism. Changes in the plasma concentrations of amino acids did not reflect necessarily the concentrations in muscle tissue.
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PMID:Amino acid concentrations in plasma and skeletal muscle of patients with acute hemorrhagic necrotizing pancreatitis. 401 35

Cachexia as a consequence of a catabolic state (stress metabolism) and cachexia as a consequence of too small food intake (inanition metabolism) have to be distinguished from each other fundamentally. A typical amino acid distribution in plasma, muscle, and liver can be observed in the protein catabolic patient. The glutamine metabolism seemed to be of special interest in the severe catabolic patient (e. g. sepsis). Glutamine is the amino acid with the biggest part of the free amino acid pool. This glutamine pool is reduced in the protein catabolic patient. A connexion seems to exist between the lower muscle glutamine concentration and the prognosis of the patient. The parenteral nutrition can stimulate the protein synthesis, but not suppress the protein hydrolysis. Perhaps catabolic factors as, for instance, interleucine I take part in that. These stimulate the protein hydrolysis over the prostaglandin metabolism.
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PMID:[Changes in protein metabolism in cachexia and catabolism]. 403 25

Nitrogen flux across the splanchnic bed is altered following operation, injury, and sepsis, but the individual contributions of gut and liver and their interrelationships remain undefined. Since more than 60% of whole blood amino acid nitrogen is transported as glutamine and alanine, we determined the flux of these amino acids across the gastrointestinal tract and liver in splenectomized, awake dogs during a control period and a 2 and 4 days following a standard laparotomy. Blood flow was measured in all studies and substrate flux calculated from flow and arteriovenous and portovenous concentration differences. Portal blood flow decreased by 25% following operation from a control value of 26 +/- 2 ml/kg body weight . min to 19 +/- 2 (P less than 0.05). Total hepatic blood flow did not change significantly after operation, but the individual contributions of the hepatic artery and portal vein were altered; hepatic artery flow increased from a control value of 10 +/- 1 ml/kg . min to 23 +/- 3 (P less than 0.001). Glutamine uptake by teh gastrointestinal tract nearly doubled from a control value of 0.75 +/- 0.16 microM/kg . min to 1.31 +/- 0.13 (P less than 0.05) on postoperative day 2. This increase in flux occurred despite a diminished arterial concentration and a reduced portal blood flow, indicating that extraction of glutamine by the gastrointestinal tract was not primarily dependent on increased arterial concentration. Alanine, on the other hand, was released by the gut at a rate of 1.97 +/- 0.37 microM/kg . min in controls and decreased to 0.81 +/- 0.13 microM/kg . min (P less than 0.05) in dogs that had operation. Glutamine was released by the liver in control dogs at a rate of 1.59 +/- 0.59 microM/kg . min but switched to an organ of slight glutamine uptake (0.31 +/- 0.31, P less than 0.01) on postoperative day 2. Alanine uptake by the liver doubled from 2.94 +/- 0.29 to 5.46 +/- 0.63 microM/kg . min (P less than 0.05) following surgical stress. The gastrointestinal tract plays an active metabolic role in the processing of amino acids following operation and may be a key regulatory of interorgan substrate flux following injury and infection.
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PMID:Postoperative alteration of arteriovenous exchange of amino acids across the gastrointestinal tract. 687 48


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