Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

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

Transmucosal passage of bacteria in critically ill patients may lead to a significant incidence of systemic sepsis. This has attracted much clinical interest, as it has been shown that malnutrition in itself, impairs various aspects of barrier function. Bacterial translocation is increased in animal models where nutrients are given by the parenteral route, while enteral feeding reverses this. Translocation is also considerably increased in response to a non-lethal endotoxin challenge, if there is pre-existing protein energy malnutrition. Similar results have been obtained where the insult is caused by the inflammatory agent, zymosan. Dietary fibre reduces the deleterious effects of either agent on translocation, although the type of fibre is important. Bulk forming but non-fermentable fibres are more effective than easily fermentable types (for example, pectin). Glutamine was not effective in preventing elemental diet induced bacterial translocation. Thus, although fermentable fibre and glutamine have positive effects on mucosal mass, they do not affect translocation. Enteral nutrition thus seems to be superior to parenteral nutrition in maintaining the functional barrier of the gut. A clearer understanding of the physiology of these effects may lead to use of specifically modified enteral diets in the critically ill patient.
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PMID:Bacterial translocation: the influence of dietary variables. 812 85

Glutamine uptake by the liver is accelerated during endotoxemia, but little is known regarding the influence of sepsis on the plasma membrane transport systems catalyzing hepatic glutamine uptake. We hypothesized that this augmented uptake was due to an increase in hepatocyte plasma membrane transport activity. We investigated the activities of the Na(+)-dependent transport System N (transports glutamine into the hepatocyte) and the Na(+)-independent System n (transports glutamine out of the cell) in hepatocyte plasma membrane vesicles (HPMVs) prepared from livers of rats treated with Escherichia coli endotoxin (LPS) in vivo. HPMVs were prepared by differential centrifugation and the transport of [3H]glutamine was assayed by a rapid mixing/filtration technique in the presence and absence of sodium. Vesicle integrity and functionality were confirmed by enzyme marker enrichments and classic "overshoots" in the presence of sodium. Carrier-mediated Na(+)-independent glutamine transport activity was not altered by LPS administration. In contrast, endotoxemia resulted in a time- and dose-dependent two- to threefold increase in Na(+)-dependent glutamine transport activity in HPMVs secondary to an increase in the transport Vmax, consistent with the appearance of increased numbers of corresponding transporter proteins in the hepatocyte plasma membrane. The Km (affinity for glutamine) of the System N transporter was not affected by LPS treatment. Maximal increases in transport were observed 4 hr after exposure to endotoxin. System N transport activity returned to basal levels by 12 hr. This increase in transport activity represents an important mechanism regulating the accelerated hepatic glutamine uptake that occurs during severe infection.
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PMID:Endotoxin increases hepatic glutamine transport activity. 836 Nov 64

This study of the plasma aminogram was done on 35 patients with a moderate to high level of stress and/or sepsis. For the criteria of illness, the SAPS (Simplified Acute Physiological Score) was used on their admission to the intensive Care Unit, and the diagnosis of sepsis was established according to the criteria of Jacobs and Boone. The stress level was calculated according to Bistrian. The plasma aminogram was determined with High Resolution Liquid Chromatography. The plasma samples were taken while nutrient units containing what is considered a standard solution of amino acids were infused. The eight essential amino acids (EAA) and 10 non-essential were quantified. The ratio of ramified to aromatic amino acids (RAA/AAA) was calculated by Fisher's criteria. An increase in AAA (phenylalanine, p < 0.001, and tyrosine, NS) and sulphur containing amino acids (methionine, p < 0.001) was found. The RAA were within normal ranges (valine) or increased (leucine, p < 0.001 and isoleucine, p < 0.001). The RAA/AAA ratio was reduced, p < 0.0001. Glycine was increased, p < 0.0001 and alanine reduced, p < 0.05. Glutamine and glutamic acid were reduced, p < 0.0001 and p < 0.01 as was arginine, p < 0.001. No difference was found in the total concentration of AA. The results confirm the standard plasma aminogram described in situations of metabolic stress and/or sepsis.
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PMID:[Plasma aminogram in critical patients]. 846 96

Glutamine is important for the function of lymphocytes and macrophages. A role for the high rate of glutamine utilisation by these cells is presented. Since muscle syntheses, stores and releases glutamine, this tissue may play a role in the immune response. Since the number of immune cells utilising glutamine may be large, the demand for glutamine from muscle, especially during trauma, sepsis or burns, may be very high. A speculative suggestion is put forward that this requirement for glutamine from muscle may play a role in cachexia under some of these conditions.
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PMID:The possible role of glutamine in some cells of the immune system and the possible consequence for the whole animal. 864 82

Glutamine is a non essential amino acid. Nevertheless it has to be considered a "conditionally essential" amino acid for several metabolic reactions in which it is involved. Glutamine is the most abundant amino acid in human plasma and muscle. Because glutamine is highly unsteady, it was never used for enteral and parenteral nutrition in the past. It appears to be a unique amino acid for rapidly proliferating cells serving as a preferred fuel compared to glucose. It seems to be essential for cellular replication such as a "nitrogen carrier" between the tissues. A deficiency state of glutamine causes morphology and functional changing and negative nitrogen metabolism. The need for glutamine is particularly high when metabolism is increased as in the critically ill (surgical stress, sepsis, inflammatory states, fasten, burns) especially in the tissues with a rapid cell turn-over. In these conditions the body requirements of glutamine appear to exceed the individual's muscle deposits (muscle is the most important place of synthesis and storage), causing an increased synthesis with a high energy waste and loss of muscle mass. Glutamine is essential for bowel mucosa trophism and its deficiency in all the catabolic states allows bacterial translocation. In these cases feeding is not sufficient to restore basal conditions. At present enteral or parenteral glutamine supplementations are of high interest for the feeding of critically ill patients.
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PMID:[The metabolic role of glutamine]. 865 37

Branched chain amino acids (BCAAs) and glutamine are both recommended in catabolic states. The object of this study was to compare the efficacies of alanylglutamine (Ala-Gln)-enriched and BCAA-enriched total parenteral nutrition (TPN) on the protein kinetics in peritonitis. Rats were divided into Ala-Gln and BCAA groups after intraperitoneal implantation of an osmotic pump, delivering a continuous infusion of Escherichia coli. Glutamine composed 30.0% (w/v) of the total amino acids in the Ala-Gln group, and BCAA composed 30.5% (w/v) of the total amino acids in the BCAA group. The two solutions were isocaloric and isonitrogenous. Whole body protein turnover and organ fractional protein synthetic rates (FSR) were measured on days 3 and 5. Serum amino acid levels and mucosal morphology were determined. Ala-Gln group had higher rates of whole body protein turnover, and hepatic FSR on both days. Serum glutamine levels correlated with hepatic and muscle FSR. Ala-Gln TPN group had greater mucosal thickness, numbers of mitoses per crypt, and FSR in distal intestine. Ala-Gln-enriched TPN may be a useful nutritional treatment modality in sepsis.
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PMID:Alanylglutamine-enriched total parenteral nutrition improves protein metabolism more than branched chain amino acid-enriched total parenteral nutrition in protracted peritonitis. 904 98

Glutamine is the most abundant free amino acid of the human body. In catabolic stress situations such as after operations, trauma and during sepsis the enhanced transport of glutamine to splanchnic organs and to blood cells results in an intracellular depletion of glutamine in skeletal muscle. Glutamine is an important metabolic substrate for cells cultivated under in vitro conditions and is a precursor for purines, pyrimidines and phospholipids. Increasing evidence suggests that glutamine is a crucial substrate for immunocompetent cells. Glutamine depletion in the cultivation medium decreases the mitogen-inducible proliferation of lymphocytes, possibly by arresting the cells in the G0-G1 phase of the cell cycle. Glutamine depletion in lymphocytes prevents the formation of signals necessary for late activation. In monocytes glutamine deprivation downregulates surface antigens responsible for antigen preservation and phagocytosis. Glutamine is a precursor for the synthesis of glutathionine and stimulates the formation of heat-shock proteins. Moreover, there are suggestions that glutamine plays a crucial role in osmotic regulation of cell volume and causes phosphorylation of proteins, both of which may stimulate intracellular protein synthesis. Experimental studies revealed that glutamine deficiency causes a necrotising enterocolitis and increases the mortality of animals subjected to bacterial stress. First clinical studies have demonstrated a decrease in the incidence of infections and a shortening of the hospital stay in patients after bone marrow transplantation by supplementation with glutamine. In critically ill patients parenteral glutamine reduced nitrogen loss and caused a reduction of the mortality rate. In surgical patients glutamine evoked an improvement of several immunological parameters. Moreover, glutamine exerted a trophic effect on the intestinal mucosa, decreased the intestinal permeability and thus may prevent the translocation of bacteria. In conclusion, glutamine is an important metabolic substrate of rapidly proliferating cells, influences the cellular hydration state and has multiple effects on the immune system, on intestinal function and on protein metabolism. In several disease states glutamine may consequently, become an indispensable nutrient, which should be provided exogenously during artificial nutrition.
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PMID:[Glutamine: effects on the immune system, protein balance and intestinal functions]. 904 23

The activity of glutaminase is high in lymphoid organs, lymphocytes and macrophages and increases in the popliteal lymph node in response to an immunological challenge. Consistent with this high activity, glutamine is utilised at a high rate by resting lymphocytes and macrophages in culture. Mitogenic stimulation of lymphocytes increases both glutaminase activity and the rate of glutamine utilisation. The major products of glutamine utilisation by lymphocytes and macrophages in culture are glutamate, aspartate, lactate and ammonia; < 25% of the glutamine used is completely oxidised. It is suggested that the high rate of glutamine utilisation by cells of the immune system serves to maintain a high intracellular concentration of intermediates of biosynthetic pathways such that optimal rates of DNA, RNA and protein synthesis can be maintained. In the absence of glutamine, lymphocytes do not proliferate in vitro; proliferation increases greatly as the glutamine concentration increases. The synthesis of interleukin-2 by lymphocytes and of interleukin-1 by macrophages is glutamine-dependent. Macrophage-mediated phagocytosis is influenced by glutamine availability. Glutamine is synthesized in skeletal muscle. Skeletal muscle and plasma glutamine levels are lowered by sepsis, injury, burns, surgery and endurance exercise and in the overtrained athlete. These observations indicate that a significant depletion of the skeletal muscle glutamine pool is characteristic of trauma and it has been suggested that the lowered plasma glutamine concentration contributes, at least in part, to the immunosuppression which accompanies such situations. Beneficial effects of the provision of glutamine or its precursors have been reported in patients following surgery, radiation treatment or bone marrow transplantation or suffering from injury, sepsis or burns.
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PMID:The proposed role of glutamine in some cells of the immune system and speculative consequences for the whole animal. 926 77


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