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

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 metabolism of skeletal muscle glutamine was studied in rats made septic by cecal ligation and puncture technique. Blood glucose was not significantly different in septic rats, but lactate, pyruvate, glutamine, and alanine were markedly increased. Conversely, blood ketone body concentrations were markedly decreased in septic rats. Both plasma insulin and glucagon were markedly elevated in septic rats. Sepsis increased the rates of glutamine production in muscle, but without marked effects on skin and adipose tissue preparations, with muscle production accounting for over 87% of total glutamine produced by the hindlimb. Sepsis produced decreases in the concentrations of skeletal muscle glutamine, glutamate, 2-oxoglutarate, and adenosine monophosphate (AMP). The concentrations of ammonia, pyruvate, and inosine monophosphate (IMP) were increased. Hindlimb blood flow showed no marked change in response to sepsis, but was accompanied by an enhanced net release of glutamine and alanine. The maximal activity of glutamine synthetase was increased only in quadriceps muscles of septic rats, whereas that of glutaminase was decreased in all muscles studied. Tyrosine release from incubated muscle preparation was markedly increased in septic rats; however, its rate of incorporation was markedly decreased. It is concluded that there is an enhanced rate of production of glutamine from skeletal muscle of septic rats. This may be due to changes in efflux and/or increased intracellular formation of glutamine; these suggestions are discussed.
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PMID:Glutamine metabolism in skeletal muscle of septic rats. 167 Nov 65

The alterations in lung glutamine (GLN) metabolism that occurs in the endotoxin-injured lung were studied in rats and subsequently correlated with flux changes that occur in patients with the adult respiratory distress syndrome (ARDS). Measurements in animals were made at various time-points following the administration of endotoxin, while studies in surgical patients were done in a group of healthy controls, in patients with "early" sepsis who had normal chest x-ray films, and in patients with radiographic and physiologic evidence of ARDS. In healthy control rats, net amounts of GLN are released by the lungs into the systemic circulation. This release rate doubled 30 minutes after intravenous endotoxin (1,580 +/- 320 nmol GLN/100 g BW/min vs. 736 +/- 179 in controls, p less than 0.01) but glutamine synthetase activity was unchanged, suggesting an outpouring of cellular glutamine stores. Two hours after endotoxin treatment, this accelerated fractional release of glutamine by the lungs was no longer detected. By the 12-hour time-point, the lungs reversed to an organ of net glutamine balance (234 +/- 248 nmol/100 g BW/min, p less than 0.05 vs. controls and ENDO30 min) despite a more than two-fold increase in glutamine synthetase activity (p less than 0.01). Simultaneously, lung weights were increased by 21% (p less than 0.01) and histologic examination showed an interstitial infiltrate and pulmonary edema. Similar observations were made in humans; patients with "early" sepsis exhibited a marked increase in lung glutamine release, while patients with ARDS demonstrated glutamine balance across the lungs (4,030 +/- 910 nmol GLN/kg BW/min vs. 637 +/- 496 in ARDS, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glutamine metabolism by the endotoxin-injured lung. 167 90

1. The metabolism of glutamine and alanine in the lung was studied in rats made septic by a caecal ligation and puncture technique. 2. The blood glucose concentration was not significantly different in septic rats, but blood pyruvate, lactate, glutamine and alanine concentrations were markedly increased as compared with sham-operated rats. Conversely, blood ketone body and plasma cholesterol concentrations were significantly decreased in septic rats. Both plasma insulin and plasma glucagon concentrations were markedly elevated in response to sepsis. Sepsis resulted in a negative nitrogen balance. 3. Sepsis increased the rates of production of glutamine (52.5%, P less than 0.001), alanine (38.9%, P less than 0.001) and glutamate (48.6%, P less than 0.001) by lung slices incubated in vitro. 4. Sepsis increased lung blood flow by 27.6% (P less than 0.05). Blood flow and arteriovenous concentration difference measurement across the lung of septic rats showed an increase in the net exchange rates of glutamine (142.5%, P less than 0.001), alanine (129.4%, P less than 0.001), glutamate (100.9%, P less than 0.001) and ammonia (138.0%, P less than 0.001) as compared with sham-operated control rats. 5. Sepsis produced significant decreases in the lung concentrations of glutamine (36.8%), glutamate (20.8%), 2-oxoglutarate (64.8%) and AMP (18.3%). The lung concentrations of alanine (95.9%), ammonia (67.7%) and pyruvate (89.7%) were increased. 6. The maximal activities of glutamine synthetase (20.4%, P less than 0.05), phosphate-dependent glutaminase (18.9%, P less than 0.05) and alanine aminotransferase (25.5%, P less than 0.05) were increased, but there was no marked change in that of glutamate dehydrogenase, in the lungs of septic rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glutamine and alanine metabolism in lungs of septic rats. 168 36

The effect of ischemia on hepatic protein synthesis during sepsis is not known, but is of clinical relevance, since hepatic blood flow decreases during the late phase of sepsis. In this study, synthesis of acute-phase proteins was measured in perfused livers of rats 16 hours after sham operation or cecal ligation and puncture. Livers from each group had 45 minutes of complete ischemia or control perfusion. Protein synthesis was measured during two hour perfusion after the ischemia or control period, by determining incorporation of 3H-leucine into total secreted trichloracetic acid precipitated proteins, immunoprecipitated complement component C3 and albumin and phosphotungstenate-precipitated alpha 1-acid glycoprotein. Lactate, glutamine-oxalacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT) levels in the perfusate were measured during preischemic and postischemic perfusion. Tissue glutathione levels were measured at the end of the perfusion. Synthesis of alpha 1-acid glycoprotein was increased by 100 per cent and albumin synthesis decreased by 46 per cent in septic livers, consistent with an acute-phase response and apparent downregulation of albumin synthesis during early sepsis. Synthesis rates were reduced by 50 to 60 per cent after ischemia in perfused livers from sham operated rats and 70 to 80 per cent in livers from septic rats. Hepatic production of interleukin-1 was not different between the groups during perfusion. GOT and GPT levels increased significantly during ischemia of both nonseptic and septic livers and rapidly returned toward baseline during reperfusion. Lactate levels were higher in perfusate of septic than of nonseptic livers before ischemia and increased further during ischemia. The results suggest that ischemia inhibits production of secreted hepatic proteins similarly in nonseptic and septic livers, but perhaps to a slightly greater extent in septic livers.
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PMID:Effect of ischemia on protein synthesis in the septic liver. 170 61

The effects of cytokines on intestinal glutamine metabolism were studied to gain further insight into the regulation of altered glutamine metabolism that occurs during severe infection. One hundred thirteen adult rats were given a single dose of interleukin-1 (IL-1, 50 micrograms/kg), tumor necrosis factor (TNF, 50 micrograms/kg or 150 micrograms/kg), or saline (controls), and flux studies were performed 4 or 12 hours later. Intestinal blood flow was not different between control and cytokine-treated animals at either time point. At the 4-hour time point, arterial glutamine fell by 16% to 21% in the cytokine-treated animals (p less than 0.05); at the 12-hour time point, the arterial glutamine concentration had returned to normal. Intestinal glutamine extraction decreased in the animals treated with IL-1 at both time points (4 hours: 13% +/- 1.3% in IL-1 versus 20% +/- 1.6% in controls, p less than 0.05; and 12 hours: 9% +/- 2% in IL-1 versus 17% +/- 2% in controls, p less than 0.05). Consequently, net intestinal glutamine uptake fell in the animals treated with IL-1 at both time points (p less than 0.05). Similarly, the activity of mucosal glutaminase, the principal enzyme of glutamine hydrolysis in the gut, fell by 50% in the 4-hour study (6.1 +/- 0.6 mumol/h/mg protein in IL-1 versus 9.6 +/- 0.8 mumol/h/mg protein in controls, p less than 0.01) and by 40% in the 12-hour study (5.4 +/- 0.5 mumol/h/mg protein in IL-1 versus 8.8 +/- 0.4 mumol/h/mg protein in controls, p less than 0.05). Concomitant with the aforementioned decrease in gut glutamine metabolism was a 25% incidence of positive blood cultures for gram-negative organisms in IL-1 treated rats studied at the 12-hour time point (p = 0.05 versus controls). In the doses administered and at the time points studied, TNF had no effects on the parameters of gut glutamine metabolism examined. The results indicate that IL-1 is a potential mediator of the alterations in gut glutamine metabolism observed in sepsis and endotoxemia.
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PMID:Cytokine regulation of intestinal glutamine utilization. 173 66

Thirty dogs underwent hemorrhage over a 60-min period to a predetermined O2 debt of 60-120 mL O2/kg, monitored with a Beckman metabolic cart, and then were resuscitated with 120% of the shed volume. Twenty survived and were followed over the next 7 days. On day 4, hepatic insufficiency was suggested by an elevation in [total amino acids] and [lactate] and a decrease in [urea] and [branched-chain amino acids]/[aromatic amino acids]. Net whole body catabolism on day 4 is suggested by a decrease in [glutamine] and an increase in plasma [3-methylhistidine], [phenylalanine], and [tyrosine]. These changes were significantly related to cardiac index, mean blood pressure, [lactate], O2 debt, and shed volume during the hemorrhage 4 days earlier. On day 7 there was a significant increase in the cardiac index and the VO2. These data suggest that hemorrhage induces sequelae similar to major injury or sepsis: hepatic insufficiency, net catabolism, hypermetabolism, and a hyperdynamic circulation. The hyperdynamic circulation may be necessary to meet increased tissue delivery requirements for O2 and amino acids.
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PMID:Hepatic insufficiency and increased proteolysis, cardiac output, and oxygen consumption following hemorrhage. 177 49

The response to injury and infection can be viewed as a mobilization of body protein, fat, and carbohydrate stores to ensure normal or above-normal circulating levels of substrate in the absence of dietary intake. The situation does not readily yield to nutritional manipulation, and inappropriate nutritional support can cause additional stress. Artificial nutrition is mainly a form of nutrient administration and not nutrient utilization. Modulation of neurohumoral and wound responses to trauma due to starvation and refeeding has not been delineated. The provision of adequate substrates alone does not necessarily guarantee their efficient use in metabolism. With a clear knowledge of the role of cellular mediators in the pathophysiology of disease, it may be possible to develop more rational therapeutic approaches during critical illness. Determination of appropriate and optimal substrate support through parenteral and enteral nutrition remains of great clinical importance. The clinical application of branched-chain amino acids, dispensable amino acids, acetylated amino acids, dipeptides or tripeptides, cysteine, glutamine, and arginine has been explored in recent years. The idea that lipids are deleterious in sepsis and organ failure should be revised and documented, and recent studies suggest that fish oils as a lipid source may also favorably affect immune responses. Under stressful conditions, total parenteral nutrition can require large amounts of energy at a time when there are marked disturbances in glucose utilization. In this area, the use of nonglucose carbohydrates or oligosaccharides can be appropriate, despite the lack of broad acceptance. Existing conventional substrates should be studied beyond mere provision of energy and metabolic pathway support.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Nutritional and metabolic support: converging concepts. 180 4

Sepsis and organ failure produce profound metabolic changes that contribute to hepatic and musculoskeletal failure. When multiple organ failure develops, the mortality rate is high, and therapy is unlikely to be effective unless the causative process (e.g., infection, low cardiac output) can be eliminated. Thus, the prevention of multiple organ failure and the prevention or early treatment of infection are paramount. Organ and nutritional support to prevent complications is necessary. The gastrointestinal tract should be used for nutrition whenever possible with a blenderized regular diet with fiber, glutamine, and short-chain fatty acids to protect and preserve the gut. If parenteral nutrition is necessary, special solutions may be necessary for the liver, kidneys, or lungs. If not, protein with 45% branched-chain amino acid, medium- and short-chain triglycerides, glutamine supplementation, and carbohydrates seem best. Other substances are being evaluated that may be helpful in nutrition and organ support, including arginine, xylitol, growth hormone, and anabolic steroids. Multiple organ failure should be prevented, if at all possible, by stopping or controlling the injury, removing as much necrotic tissue as possible, improving blood flow and oxygen consumption, supporting metabolism, and preventing infection or treating it early and adequately. Nutritional support plays a key role in preventing metabolic failure.
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PMID:Nutrition and metabolism in sepsis and multisystem organ failure. 190 43


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