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

Recently a relationship has been postulated between lowered intracellular glutamine concentrations in the skeletal muscle and the rate of protein synthesis. We investigated the effect of 48 hours of parenteral nutrition supplemented with a solution containing glutamine in free or dipeptide form (alanylglutamine or glycylglutamine) on the intracellular glutamine pool in skeletal muscle and on the hind limb exchange of glutamine in dogs with sepsis after surgery. Before surgery, dogs were fasted for 48 hours. We used glutamine dipeptides as sources because they remain stable in an aqueous solution. Nutrition solutions were isocaloric (17.8 kcal/kg body weight/day on day 1 and 35.6 kcal/kg on day 2) and isonitrogenous (0.33 gm nitrogen/kg body weight/day), providing 2.6 mmol/kg body weight/day as glutamine source. During starvation, muscular free glutamine levels decreased by 41% to 10.4 mmol/L (p less than 0.001). On the second postoperative day the dogs had lowered plasma protein levels, a sharp drop in platelet count, an increase in the leukocyte count, and positive blood cultures. None of the solutions investigated in this study was effective in repleting the glutamine pool during 2 days of postoperative nutrition (11 +/- 2.0 mmol/L without glutamine, 10.3 +/- 2.2 mmol/L with glutamine plus alanine, 9.9 +/- 1.6 mmol/L with alanylglutamine, 7.5 +/- 1.1 mmol/L with glutamine plus glycine, and 7.2 +/- 1.2 mmol/L with glycylglutamine, respectively). The release of glutamine from the hindquarter was 631 +/- 38 nmol/kg body weight/min in the control group and decreased significantly in dogs receiving alanylglutamine (13.5 +/- 45 nmol/kg body weight/min; p less than 0.001) or the constituent amino acids (265 +/- 66 nmol/kg body weight/min; p less than 0.01) but was unchanged in dogs receiving glycylglutamine or glutamine plus glycine. We conclude that the duration and dosage of glutamine administration (equivalent to 26 gm glutamine per day in a patient weighing 70 kg) used in this study are not sufficient to restore glutamine deficiency of the skeletal muscle in the depleted state.
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PMID:Glutamine-containing dipeptides as infusion substrates in the septic state. 251 Mar 34

The effect of sterile inflammation and sepsis on the release of lactate and amino acids by peripheral tissues was investigated by removing the splanchnic organs (liver and small intestines) from the circulation and monitoring changes in plasma substrates for 30 min. Functional hepatectomy was performed in rats 5-7 days following the intraperitoneal introduction of a fecal-agar pellet (1.5 ml) [sterile vs. Bacteriodes fragilis (10(8) CFU) + E. coli (10(3) CFU)]. Following functional hepatectomy, dichloroacetate, an activator of the pyruvate dehydrogenase complex, significantly inhibited both lactate and alanine release. L-cycloserine, an inhibitor of alanine aminotransferase, significantly (P less than .05) reduced alanine following hepatectomy. Methionine sulfoximine, an inhibitor of glutamine synthetase, significantly (P less than .005) decreased glutamine accumulation following functional hepatectomy in each of the conditions examined. Treatment with each of these drugs abolished the differences between control and sepsis following hepatectomy. These results demonstrate that alterations in the amino acid profiles during sepsis may be modulated in peripheral organs pharmacologically by utilizing known inhibitors of critical regulatory enzymes.
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PMID:Pharmacologic modulation of increased release of gluconeogenic precursors from extra-splanchnic organs in sepsis. 257 28

Hypoglycemia associated with renal failure is more common than generally thought. Its occurrence is often a marker of multisystem failure and has an ominous prognostic implication. Its pathogenesis is frequently complex and involves one or several mechanisms. In the evaluation of uremic hypoglycemia, the first step should be the exclusion of obvious causes such as insulin, oral hypoglycemic agent therapy, and the use of drugs known to cause hypoglycemia. Propranolol, salicylates, and disopyramide are among the most commonly implicated agents. Additional triggering events are alcohol consumption, sepsis, chronic malnutrition, acute caloric deprivation, concomitant liver disease, congestive heart failure, and an associated endocrine deficiency. When no obvious cause can be demonstrated, the hypoglycemia is referred to as spontaneous. Spontaneous uremic hypoglycemia has been attributed to deficiency of precursors of gluconeogenesis, that is, alanine, deficient gluconeogenesis, impaired glycogenolysis, diminished renal gluconeogenesis and impaired renal insulin degradation and clearance, poor nutrition, and, in a few cases, deficiency in an immediate counterregulatory hormone such as catecholamine and glucagon. However, the mechanism(s) seems to differ from one patient to the other. Dialysis also predisposes to hypoglycemia in uremia, possibly because of the chronic state of malnutrition. Postdialysis hypoglycemia is secondary to glucose-induced hyperinsulinemia, which is caused by the high glucose content in the dialysate. In uremic hypoglycemia, neuroglycopenic manifestations predominate because of frequent autonomic nervous system dysfunction and lack of catecholamine release in response to hypoglycemia. Its severity and duration are variable. Hypoglycemia should be suspected in any patient with renal failure who exhibits any change in mental or neurologic status. Detection of hypoglycemia should rely on frequent and careful glucose determinations in any patient with uremia.
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PMID:Hypoglycemia associated with renal failure. 264 22

The effect of sterile inflammation and chronic sepsis on the plasma and hepatic free amino acid concentrations was determined. Relative to control animals, only minor alterations in the plasma amino acid concentrations were observed in sterile inflammation and sepsis. In liver, concentrations of alanine, serine, threonine, asparagine, proline, and glycine were significantly increased to the same extent in sterile inflammation and sepsis, while hepatic glutamine concentrations were significantly decreased. Compared with sterile inflammation, the branched-chain amino acid concentrations were depressed in the liver of septic animals. Following administration of dichloroacetate, hepatic alanine concentrations were significantly reduced more than threefold in each of the conditions examined; in contrast, significant increases in hepatic concentrations of threonine, glycine, glutamine, glutamate, histidine, and proline were observed. Also following administration of dichloroacetate, the branched-chain amino acid concentrations were all significantly elevated in each of the conditions examined, and plasma alanine concentrations were significantly decreased, while those of glutamine and glycine were significantly increased. These results demonstrate that there is a disassociation between the plasma and hepatic concentration of free amino acids in sterile inflammation and sepsis. Furthermore, the results demonstrate that some of the alterations in hepatic amino acid metabolism may be reversed pharmacologically by dichloroacetate.
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PMID:Effect of dichloroacetate on plasma and hepatic amino acids in sterile inflammation and sepsis. 267 41

The effect of sterile inflammation and sepsis on the release of lactate and amino acids by peripheral tissues was investigated in rats by removing the splanchnic organs (liver + small intestines) from the circulation and monitoring changes in blood metabolites over 30 min. Functional hepatectomy was performed in rats 5-7 days following the intraperitoneal introduction of a fecal-agar pellet (sterile vs. Bacteroides fragilis + E. coli). Lactate was significantly (P less than .05) increased in each of the conditions following hepatectomy but was raised to a significantly greater extent in sepsis (P less than .05). A similar response was observed for glutamine while alanine was only significantly (P less than .05) increased in sepsis following hepatectomy. Branched chain amino acids (BCAA) showed differential changes in sepsis compared to control. In control and sterile inflammation, functional hepatectomy was associated with significant decreases (P less than .05) in BCAA. In sepsis, BCAA were not decreased following hepatectomy and were significantly (P less than .05) elevated relative to control or sterile inflammation. Phenylalanine concentrations were not altered in control or sterile inflammation but were significantly elevated in sepsis (P less than .05). Insulin attenuated the accumulation of lactate and amino acids in fed control animals, following functional hepatectomy. However, in septic animals, insulin failed to prevent the rise in plasma lactate following hepatectomy.
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PMID:Role of extra-splanchnic organs in the metabolic response to sepsis: effect of insulin. 267 32

Previous studies with neutrophils from patients with intra-abdominal sepsis have provided convincing evidence of in vivo exposure to C5a. However, in contradistinction to normal cells pretreated with C5a, patient cells showed depressed superoxide response to N-formyl-methionyl-leucyl-phenyl-alanine (FMLP) and enhanced FMLP receptor affinity. To identify possible mechanisms responsible for these findings, we examined the effects of lysosomal alkalinization with the weak base clindamycin on normal neutrophils with and without C5a. Our results showed a specific suppression of FMLP-induced superoxide production and a loss of low-affinity FMLP receptors. These results occurred in the presence of clindamycin levels that did not interfere with other cellular processes. These findings suggest that regulation of neutrophil function during the course of intra-abdominal sepsis may be due to effectors active both at the cell surface (C5a) and within the lysosome. The clinical significance of our findings relates to a possible mechanism for specific pharmacologic suppression of oxide-radical production by neutrophils. Such oxide radicals are believed to be important in the capillary injury accompanying severe sepsis.
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PMID:Degranulation inhibition. A potential mechanism for control of neutrophil superoxide production in sepsis. 300 97

The hypothesis has been advanced that the human systemic septic response is a function of the host and not of the type of infecting organism. Metabolic and physiologic data from five immunosuppressed transplant recipients with isolated cytomegaloviral sepsis and viremia were prospectively evaluated. Serial cultures obtained from lung, sputum, urine, wound, blood, and invasive lines were positive for virus and negative for bacterial or fungal pathogens. The results were compared with two data banks derived from either victims of multiple trauma without sepsis or surgical patients with early bacterial or fungal sepsis. Statistically significant differences between the patients and the nonseptic reference group were noted for cardiac index, total peripheral resistance, arteriovenous oxygen content difference, oxygen consumption, and levels of triglycerides, proline, phenylalanine, tyrosine, alpha-aminobutyrate, and alanine. No such differences were present for these data compared with the septic reference group. Physiologic data obtained just before death in three patients indicated a failure of oxygen transport. It appears that the systemic septic response to viral agents is indistinguishable by physiologic and metabolic criteria from that resulting from bacterial or fungal agents.
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PMID:Physiology and metabolism in isolated viral septicemia. Further evidence of an organism-independent, host-dependent response. 302 82

Since sepsis places increased demands on the host for energy and on other substrates for tissue repair and host defense, hepatic gluconeogenesis is critical for the host's adaptation to sepsis. Substrate-stimulated gluconeogenesis (i.e., gluconeogenic capacity) was assessed by the alanine load method in mannoheptulose-pretreated rats made septic by cecal ligation after laparotomy, as well as by cecal ligation and puncture after laparotomy. Fasted rats subjected to laparotomy only (sham-ligated) and fasted, nonoperated rats (controls) were investigated simultaneously. Following an overnight (-18 to 0 hr) fast, nonoperated animals converted 17.9 +/- 1.5% of [14C]alanine to [14C]glucose. Continued fasting in nonoperated animals resulted in enhanced (P less than 0.05) gluconeogenic capacity (6 hr = 27.2 +/- 3.0%; 24 hr = 26.2 +/- 1.9%; and 48 hr = 28.5 +/- 2.6%) relative to Time 0. Laparotomy alone (sham ligation) delayed the fasting-induced increase (P less than 0.05) in gluconeogenesis capacity (6 hr = 21.1 +/- 1.2%; 24 hr = 18.5 +/- 1.3%; 48 hr = 27.8 +/- 1.0%) relative to Time 0. In contrast, postoperative sepsis produced a sustained depression (P less than 0.05) of gluconeogenic capacity relative to nonoperated sham-ligated controls at 48 hr (cecal ligation, 18.4 +/- 1.4%; and cecal ligation and puncture, 18.8 +/- 1.2%). Thus, (1) fasting enhances hepatic gluconeogenic capacity; (2) surgical trauma transiently blunts the gluconeogenic response to fasting; and (3) sepsis undermines the gluconeogenic response to fasting.
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PMID:Effect of bacterial sepsis on gluconeogenic capacity in the rat. 304 7

Eleven acute rejections were found in 9 patients with liver transplantation due to end-stage liver cirrhosis. The rejections were diagnosed with fine-needle aspiration biopsy (FNAB) giving the cellular picture of immunoactivation in the liver graft when compared to a simultaneous sample of peripheral blood. s-Alkaline phosphatase and s-bilirubin increased within 1 week after onset of rejection in 7 and 10 cases, respectively. s-Alanine amino-transferase and b-ammonium were of no value in the diagnosis of acute rejection. A core biopsy was obtained only in a case of severe liver damage, mainly to estimate the need for retransplantation. One year after grafting, 6 out of 7 cirrhotic patients are well, all with normal liver function. Two have died of sepsis. One patient died from pulmonary metastases of occult liver carcinoma 6 months after the transplantation. FNAB seems helpful in detecting early acute rejection and also excluding such an event in the liver graft.
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PMID:Diagnosis of acute rejection in liver transplantation. 304 94

Thermal injury produces profound pathophysiological changes in the severely burned patient. Primary among these is the modulation of immunity, leading to episodes of immunosuppression and thus increasing the risk of sepsis and possible death. We herein report the isolation of a low molecular weight suppressor active peptide (SAP) which appears to be responsible for many of the observed immunologic changes in burned patients. SAP suppressed T-lymphocyte blastogenesis in the mixed lymphocyte reaction (MLR) and inhibited neutrophil chemotaxis (CTX) in vitro. Characterization of SAP revealed a complex structure comprised of (1) a peptide component rich in glycine, serine, and alanine; (2) a carbohydrate component containing sialic acid; and (3) a fatty acid component, tentatively identified as prostaglandin E. The immunosuppressive activity of SAP is dependent upon the presence of all three structural components. The molecular weight of SAP was estimated to be 3654 as determined by Amicon cell ultrafiltration and amino acid analysis. The isoelectric point of SAP was estimated by chromatofocusing and ion-exchange chromatography to be between 3.2 and 3.6. We hypothesize that the suppressor active peptide may be comprised of cellular or tissue components released into the circulation at the time of injury.
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PMID:Suppression of in vitro lymphocyte and neutrophil responses by a low molecular weight suppressor active peptide from burn-patient sera. 315 47


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