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

Improvements in surgical management and intensive care therapy have enabled many patients to initially survive severe life-threatening trauma or major surgical procedures only to die after delayed bouts of sepsis. This paper reviews literature published within the past year on the effects of nutrient substitution on malnutrition, injury, and the host immune response. Topics discussed include immunodeficiencies in trauma and malnutrition, immunomodulation by nutrition, and parenteral versus enteral nutrition. We also discuss the roles of arginine, glutamine, omega-3 fatty acids, and dietary nucleotides in the host immune response.
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PMID:Malnutrition, injury, and the host immune response: nutrient substitution. 758 22

Reduced concentrations of glutamine (GLN) in plasma and skeletal muscle, defective host defense systems, and a diminished expression of the HLA-DR antigen on monocytes are important diagnostic parameters for late post-injury sepsis. In this in vitro study, we investigated whether blood monocyte-derived macrophage antigen expression and function from healthy donors is influenced by GLN. Lowering the GLN concentration in culture medium from 2 mmol/L to 200 mumol/L reduced the expression of HLA-DR by 40% (P < .001) on monocyte-derived macrophages, and decreased tetanus toxoid-induced antigen presentation. In addition, low GLN levels downregulated the expression of intercellular adhesion molecule-1 (ICAM-1/CD54), Fc receptor for IgG (Fc gamma RI/CD64), and complement receptors type 3 (CR3; CD11b/CD18) and type 4 (CR4; CD11c/CD18). A correlation was found between the phagocytosis of IgG-sensitized ox erythrocytes or opsonized Escherichia coli and the decreased expression of Fc gamma RI and CR3. Monocyte expression of CD14, CD71, and Fc gamma RIII/CD16 and capacity to phagocytose latex beads were not affected by altering the level of GLN. Depletion of GLN was associated with a significant reduction in cellular adenosine triphosphate (ATP), which may have influenced cell surface marker expression and phagocytosis. It remains to be seen whether these in vitro findings are of clinical significance in the treatment of sepsis.
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PMID:Influence of glutamine on the phenotype and function of human monocytes. 763 65

Catabolic illness such as sepsis and injury induce profound changes in host amino acid metabolism, including increased hepatic amino acid uptake. Because many amino acid-dependent pathways such as gluconeogenesis and acute-phase protein synthesis are activated in the liver during severe infection, this review will focus on the control of hepatic plasma membrane amino acid transport by specific inflammatory mediators. We specifically review the role of cytokines, eicosanoids, and glucorticoids in this response. Collectively, these signaling molecules act in a concerted manner to exert local control of hepatic function including the stimulation of amino acid transport. In particular, we review the role of glutamine and its transport in the liver, as it occupies a unique role in interorgan ammonia metabolism during critical illness.
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PMID:Hepatic uptake of glutamine and other amino acids during infection and inflammation. 764 31

The gastrointestinal tract is a major immunologic organ that must be maximally supported during critical illness. Gastrointestinal tissues require direct contact with nutrients to support their own rapid cellular turnover rate and carry out the multitude of metabolic and immunologic functions needed for successful adaptation to stress. Disruption in the ecologic equilibrium of the gastrointestinal tract often occurs during critical illness and the therapies provided. Problems encountered include stress ulcers, intestinal ischemia, bacterial overgrowth, aspiration pneumonia, bacterial translocation, sepsis, and the systemic inflammatory response syndrome. Early enteral nutrition has been shown to be a viable, economic, and physiologically beneficial way to support the gastrointestinal tract during critical illness. The fortification of enteral formulas with glutamine, arginine, or fiber is being studied to determine each one's unique role in the gut and immunologic changes that occur with severe stress.
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PMID:The role of the gut in critical illness. 774 36

The effects of endotoxin on the activities of the major Na(+)-independent amino acid transporters in rat liver (Systems n, asc, L, bo,+, and y+) were studied using using hepatic plasma membrane vesicles (HPMVs). Rats were treated with a single dose of Escherichia coli endotoxin (E. coli lipopolysaccharide 0127:B8 (LPS), 7.5, 15, or 30 mg/kg BW) and HPMVs were prepared by Percoll density gradient centrifugation at various timepoints after LPS administration. Vesicle purity and integrity was established by assay of enzyme markers and identical equilibrium uptakes. The activities of the Na(+)-independent amino acid transport systems y+ and bo,+ (arginine), asc (alanine and cysteine), L (leucine), and n (glutamine) were evaluated by measuring the uptake of radiolabeled amino acids using a rapid mixing/filtration technique. Amino acid uptake by HPMVs consisted of saturable and nonsaturable components. Prior treatment with endotoxin did not alter the activities of Systems n, asc, or L but resulted in a time- and dose-dependent stimulation of saturable arginine transport. Arginine transport increased within 2 h of LPS administration and exhibited a return towards basal levels by 24 h. Nonsaturable uptake (diffusion) in HPMVs was unaltered by LPS treatment. Kinetic analysis of arginine transport demonstrated the presence of both a high affinity and a low affinity carrier. Treatment with LPS resulted in a 73% increase in the Vmax of the high affinity carrier (System y+) and a 25% increase in the Vmax of the low affinity transporter (System bo,+). The data indicate selective stimulation of Na(+)-independent arginine transport in the liver during endotoxemia which may serve to support important arginine-dependent pathways during sepsis.
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PMID:Hepatic Na(+)-independent amino acid transport in endotoxemic rats: evidence for selective stimulation of arginine transport. 774 45

Hepatobiliary dysfunction in patients receiving nutrition support is frequent. Other reasons for elevated enzyme levels including drugs, recent anesthesia and surgery or sepsis often coexist. Liver test abnormalities in adults are usually milder than in children and frequently self-limited and are 10 times more likely to occur with total parenteral nutrition (TPN) than tube enteral nutrition. Patients on short-term TPN usually have mild-to-moderate elevations in transaminase and alkaline phosphatase levels and steatosis or portal triaditis on biopsy. Patients who are infected while on TPN are at greater risk of developing steatosis and intrahepatic cholestasis. Strategies to correct abnormalities include alteration of the caloric mix in the TPN, cyclic infusions, metronidazole, enteral nutrition and inclusion of L-glutamine in the TPN formula. Patients on long-term home parenteral nutrition may develop persistent elevations in liver tests and steatohepatitis. Both acalculus and calculus cholecystitis occur with increased frequency in patients on long-term TPN. Biliary sludge precedes calcium bilirubinate stones: predisclosing factors include nil per os, prior ileal resection and use of narcotics or anticholinergics.
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PMID:Hepatobiliary complications in adults receiving nutrition support. 785 Sep 98

Bacterial translocation (BT) of enteric organisms is a major cause of sepsis in patients undergoing small bowel transplantation (SBT). Cyclosporine (CsA) may be toxic to intestinal epithelium and increase the risk of BT. Glutamine (Gln) is the preferred enterocyte fuel and maintains graft epithelial integrity in experimental SBT. This study determined the effects of CsA on mucosal structure and function of transplanted intestinal isograft and examined whether Gln-enriched diet reversed CsA-induced intestinal toxicity. Thirty-three adult Lewis rats underwent resection of the distal 60% of small bowel and received an orthotopic jejunal isograft. Rats received either elemental diet with 2% Gln or the same diet with balanced nonessential amino acids (non-Gln) by gastrostomy for 10 days. CsA (15 mg/kg, im) or olive oil was injected daily. Rats were assigned to four groups: non-Gln with vehicle, non-Gln with CsA, Gln with vehicle, and Gln with CsA. Mucosal villous height, surface area, crypt depth, 14C glucose absorption, BT to mesenteric lymph nodes (MLN), and body weight change were evaluated. The non-Gln with CsA group had the highest incidence of BT (P < 0.001). Gln groups had significantly decreased BT (P < 0.01) and increased crypt depth and villous surface area (P < 0.01) when compared to non-Gln groups. Body weight significantly decreased in CsA groups when compared to non-CsA groups (P < 0.01). These results indicate at CsA significantly decreased body weight and increased BT without decreasing mucosal structure and glucose absorption of intestinal isografts.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glutamine reduces bacterial translocation after small bowel transplantation in cyclosporine-treated rats. 786 67

This study was performed to evaluate the effect of lactose induced diarrhea on the key enzymes of glutamine metabolism in skeletal muscle and small intestine, in rats. As compared to weight paired controls, animals with diarrhea presented higher muscle glutamine synthetase activity associated with reduced skeletal muscle glutamine concentration with a fall in arterial glutamine and an increased intestinal glutaminase activity. These alterations are similar to those reported by others in conditions in which accelerated muscle proteolysis is likely to occur such as in sepsis and after surgery. Besides the data suggestive of an overall alterations in glutamine metabolism, an important finding of this study was the increase in specific activity of intestinal phosphate dependent glutaminase in rats with diarrhea. This enzyme has been shown not to respond to many conditions such as acidosis, alkalosis or increased glutamine ingestion through drinking water or diet.
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PMID:Effect of lactose induced diarrhea on intestinal glutaminase and muscle glutamine synthetase activities in rats. 790 81

The effects of administering total parenteral nutrition (TPN) supplemented with the dipeptide of L-alanyl-L-glutamine (Ala-Gln) on gut structure, barrier function, and protein metabolism were investigated in septic rats. Sepsis was induced by the continuous intraperitoneal administration of endotoxin via a miniosmotic pump. Twenty-three rats were divided into two groups and fed parenterally for 5 days. The Ala-Gln group (n = 11) received a conventional TPN solution supplemented with 2% Ala-Gln, whereas the control group (n = 12) received conventional TPN solution alone. One rat in each group died of endotoxemia. The groups showed similar nitrogen balance, urinary excretion of 3-methylhistidine, and plasma concentration of endotoxin in the portal vein. The groups showed similar incidence of bacterial translocation from the gut to the mesenteric lymph nodes. The intestinal mucosal weight and villous height were significantly greater in the Ala-Gln group than in the control group. Pathological derangement of the mucosal structure was more marked in the control group than in the Ala-Gln group. These results suggest that TPN supplemented with Ala-Gln preserves the gut structure without decreasing the nitrogen balance under septic conditions.
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PMID:Total parenteral nutrition supplemented with L-alanyl-L-glutamine and gut structure and protein metabolism in septic rats. 791 76

Gut fuel utilisation has several unique features. Arterial and luminal fuels provide nutrition for the enterocyte, the former being of more importance. This factor, and the heterogeneity of cell types within the gut makes it difficult to define its fuel utilisation. Metabolic control logic suggests that modulation of the maximal activity of any pathway resides in those enzymes that operate in vivo at rates far below their maximal capacity and that catalyse non-equilibrium reactions. On this basis, although enterocyte hexokinase activity is much higher than in other 'glycolytic' cells (for example, brain), potentially high rates of glucose utilisation are modulated by substrate cycling of glucose 6-phosphate back to glucose through glucose 6-phosphatase. Glutamine metabolism proceeds by glutaminase to produce glutamate, which may then be transaminated (aspartate-aminotransferase and alanine-amino transferase) to produce alpha-ketoglutarate, alanine, and aspartate. The end products of glutamine metabolism by incubated gut preparations in vitro (mainly alanine), suggests that enterocytes, not immune cells, are responsible for most gut glutamine metabolism. High flux rates of glucose and glutamine metabolism in the enterocyte may result from the need for de novo synthesis of purines and pyrimidines and ribose sugars for nucleic acid synthesis. Sepsis reduces rates of glucose and glutamine metabolism, perhaps to preserve the increased consumption of these fuels by activated lymphocytes and macrophages in the gut wall.
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PMID:Quantitative aspects of glucose and glutamine metabolism by intestinal cells. 812 83


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