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

The rate of leucine C-2 incorporation into glutamine was compared in control and septic rats. Female Sprague-Dawley rats (n = 46, 210-260 g) were fed parenterally for 3 days and then randomized into two groups (control and septic). Sepsis was induced by the injection of 10(10) live Escherichia coli/kg on day 4 into the septic group. Rats in each group were given a continuous (8 h) infusion of one of three different isotopes. The isotopes were given 24 h after inoculation. Leucine oxidation and incorporation into protein were determined with [1-13C]leucine; glutamine flux and oxidation were determined with [5-13C]glutamine, and the fraction of leucine C-2 incorporated into glutamine was determined by giving [1,2-13C]leucine. Results were as follows: sepsis caused a significant increase in the rate of leucine C-2 incorporation into glutamine (66.0 +/- 3.7 as against 29.6 +/- 3.7 mumol/h per kg, P less than 0.01). This increase was due to both an increase in glutamine production (2331 +/- 76 as against 1959 +/- 94 mumol/h per kg, P less than 0.01) and an increase in the proportion of glutamine derived from leucine (2.83 +/- 0.27% as against 1.51 +/- 0.31%, P less than 0.01). The ratio of leucine C-2 incorporated into glutamine to leucine oxidized increased from 7.16 +/- 0.91% to 11.49 +/- 1.12% with sepsis (P less than 0.05).
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PMID:Leucine and glutamine metabolism in septic rats. 190 18

The traditional approach to the care of the gastrointestinal tract in the intensive care unit has been one of neglect. However, recent evidence has linked enteric flora to the generation of clinical sepsis in the absence of other infectious foci. The role of the bowel as an efficient barrier to the invasion of its own flora is addressed in this paper. A variety of insults disrupt the integrity of the barrier function of the gut, allowing the entry of bowel organisms or endotoxins, or both, into the portal and systemic circulatory systems. In animal and early clinical studies, a number of interventions, aimed at altering the enteric flora and enhancing the bowel's barrier function, have been shown to modulate the host's resistance to different insults and may even improve clinical outcome. Such interventions include maintenance of enteral feeding, glutamine supplementation of hyperalimentation solutions and selective bacterial decontamination of the bowel.
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PMID:Care of the gut in the surgical intensive care unit: fact or fashion? 190 91

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

This study was performed to investigate the interrelationship between gluconeogenesis and ureagenesis during sepsis. In isolated perfused livers, gluconeogenesis was assessed using either lactate or a combination of lactate, glutamine, and alanine as substrate. Ureagenesis was assessed using either NH4Cl or glutamine plus alanine as substrate. NH4Cl stimulated urea production in livers from both septic and sham-operated control rats. Urea release was approximately 1.2 and 2.0 mg urea nitrogen.g-1.h-1 for 1 and 5 mM NH4Cl, respectively, and was equal for both groups. With amino acids as substrate, urea production was significantly greater in livers from septic animals compared with controls. Phenylephrine stimulated urea production in the sham-operated group by about twofold, whereas in the septic group urea release was slightly inhibited. Gluconeogenesis from lactate was inhibited by NH4Cl (1 and 5 mM) in both groups, with no difference between groups. In contrast to enhanced ureagenesis from amino acids in septic rats, gluconeogenesis was decreased by approximately 24% (P less than 0.5). Similarly, phenylephrine (1 microM) stimulated gluconeogenesis by 13 +/- 1 mumol.g-1.h-1 in sham-operated rats but only by 9 +/- 1 mumol.g-1.h-1 in septic rats (P less than 0.02). These results suggest that hepatic gluconeogenic and ureagenic pathways are intact in sepsis but that altered substrate preference and hormone sensitivity may result in decreased gluconeogenesis in the presence of elevated amino acid levels.
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PMID:Interrelationship between hepatic ureagenesis and gluconeogenesis in early sepsis. 200 98

The activity of phosphate-dependent glutaminase and glutamine metabolism by tissues known markedly to utilize or synthesize glutamine (or both) were studied in rats made septic by cecal ligation and puncture technique and compared with the same measures in rats that underwent sham operation (laparotomy). Blood glucose level was not markedly different in septic rats, but lactate, pyruvate, alanine, and glutamine levels were markedly increased. Conversely, blood ketone body concentrations were significantly decreased in septic rats. Both plasma insulin and glucagon levels were markedly elevated in response to sepsis. The maximal activity of phosphate-dependent glutaminase was decreased in the small intestine, increased in the kidney and mesenteric lymph nodes, and unchanged in the liver of septic rats. Arteriovenous concentration difference measurements across the gut showed a decrease in the net glutamine removed from the circulation in septic rats. Arteriovenous concentration difference measurements for glutamine showed that both renal uptake and skeletal muscle release of the amino acid were increased in response to sepsis, whereas measurements across the hepatic bed showed a net uptake of glutamine in septic rats. Enterocytes isolated from septic rats exhibited a decreased rate of utilization of glutamine and production of glutamate, alanine, and ammonia, whereas lymphocytes isolated from septic rats showed an enhanced rate of utilization of glutamine and production of glutamate, aspartate, and ammonia. It is concluded that, during sepsis, glutamine uptake and metabolism are enhanced in renal and lymphoid tissue but decreased in that of the small intestine, with increased rates of release by skeletal muscle; however, the liver appears to utilize glutamine in septic rats.
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PMID:Maximal activity of phosphate-dependent glutaminase and glutamine metabolism in septic rats. 206 39

In the critically ill surgical patient a variety of therapeutic maneuvers is required to maintain a "healthy gut." Provision of adequate amounts of glutamine to the gastrointestinal mucosa appears to be just one of these maneuvers. Other methods utilized to protect the gut from becoming a wound include: (a) minimizing additional systemic insults (such as hypotension, sepsis, multiple operative procedures); (b) aggressive pulmonary care; (c) the judicious use of antibiotics; and (d) aggressive enteral or parenteral feedings. The concept that the gut is an organ of quiescence following surgical stress merits reconsideration. The intestinal tract plays a central role in interorgan glutamine metabolism and is a key regulator of nitrogen handling following surgical stress. Critically ill patients are susceptible to developing gut-origin sepsis, the incidence of which will be diminished by instituting measures and providing treatments which support intestinal structure, function, and metabolism. Provision of glutamine-enriched diets to such patients may be one of these therapies.
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PMID:The role of glutamine in maintaining a healthy gut and supporting the metabolic response to injury and infection. 218 15

Critical illness initiates some of the most profound alterations in interorgan glutamine metabolism observed in the laboratory as well as in clinical medicine. The interorgan flow becomes markedly altered and net glutamine utilization exceeds production, leading to glutamine depletion in several organs and a possible impairment of protein synthesis. As the patient recovers from the operation or sepsis, it appears that the flow of glutamine between tissues slowly reverts to "normal." During this process, food intake is resumed, the wound heals, activity generally returns to preillness levels, and, in most circumstances, the person is again well.
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PMID:Interorgan glutamine flow following surgery and infection. 220 36

Tumor necrosis factor (TNF), a polypeptide produced predominantly by activated macrophages, is an important mediator of sepsis. We analyzed the specific metabolic changes that occur in the gut following TNF administration. Following general anesthesia, hemodynamic and metabolic indices were measured serially in control dogs (n = 7) and animals receiving a continuous sublethal intravenous infusion of TNF (0.57.10(5) IU/kg/6 hours, n = 7). During TNF infusion mean arterial pressure gradually decreased despite fluid administration, which maintained wedge pressure and cardiac index, which were similar to control animals. While TNF significantly reduced intestinal blood flow to 12 +/- 3 mL/min/kg compared to 28 +/- 3 mL/min/kg (p less than 0.01) in controls, intestinal oxygen consumption was maintained due to an increased extraction rate. Despite hypoperfusion the intestinal exchange of metabolic substrate (glucose, lactate, pyruvate, alanine, glutamine, glutamate, and ammonia) was comparable between the control and TNF-infused animals. However, when substrate carbon balance across the intestinal tract was calculated, it appeared that there was a limitation in fuel availability in the TNF animals. This may be due to competition for fuel between the gut and other major organs. Fuel limitation may jeopardize rapid cell proliferation and mucosal repair and with regional hypoperfusion these processes may account for the mucosal ulcerations observed at the termination of the study.
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PMID:The effects of tumor necrosis factor on intestinal structure and metabolism. 225 57

We elected to test the hypothesis that the metabolic encephalopathy associated with systemic sepsis may have a pathogenesis that is similar to hepatic encepathology, ie, as the consequence of hepatic dysfunction that induces alterations in synthesis of catecholic and noncatecholic neurotransmitters. Eleven patients with septic encephalopathy were compared with nine patients with septic encephalopathy and nine normal controls with respect to blood and cerebrospinal fluid (CSF) amino acid profile, phenylethylamine and its metabolite phenylacetic acid, and blood ammonia. Blood and CSF levels of phenylacetic acid increased markedly in septic and hepatic encephalopathy while CSF phenylethylamine levels were not increased in either condition, presumably due to rapid turnover. The CSF concentrations of all the aromatic amino acids were increased in hepatic encephalopathy, whereas in the patients with sepsis, only phenylalanine levels were increased. Evidence of stimulated neutral amino acid transport into brain was demonstrated in hepatic not septic encephalopathy and appeared to correlate with the CSF glutamine concentration. Blood ammonia levels were increased in hepatic but not in septic encephalopathy. Our data support the hypothesis that metabolites of phenylethylamine contribute to encephalopathy in systemic sepsis and hepatic failure; however, the entities differ in other respects.
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PMID:Septic encephalopathy. Evidence for altered phenylalanine metabolism and comparison with hepatic encephalopathy. 230 19


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