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

The plasma concentrations of substrates, together with transhepatic and transgut balances, have been studied in six control and eight septic awake fasted dogs. Four severely ill septic dogs (typically fluid in chest and/or abdomen, extensive peritonitis, respiratory difficulties) had high concentrations of threonine, glycine, tyrosine, lysine, histidine, tryptophan, and triglycerides (p less than or equal to 0.05). The other septic dogs (less severely ill) showed fewer and less pronounced alterations in the plasma substrates (aspartate and tryptophan were elevated, p less than or equal to 0.05). The infusion of glucose increased the concentration of glucose, lactate, and pyruvate and depressed the concentrations of most amino acids in both normal and septic dogs. Threonine, asparagine, glutamine, leucine, isoleucine, alpha-aminobutyrate, and tyrosine were significantly depressed in the severely ill septic dogs (p less than or equal to 0.05). In the normal dogs most amino acids were removed by the liver, with alanine accounting for approximately 40% of the total. Glutamine removal was negligible. In the septic dogs hepatic removal of amino acids was variable; livers of two severely ill septic dogs did not remove amino acids. In the control dogs glucose infusion (0.015--0.017 g/kg/min) tended to lower hepatic removal of amino acids. Hepatic dye removal in the septic dogs was always very poor. In the gut glutamine was removed and alanine, glutamate, glycine, and ammonia produced, but the overall sum of amino acid uptake was negligible in both the control and septic dogs. The ratio of tryptophan to the sum of valine, isoleucine, leucine, tyrosine, and phenylalanine concentrations was greatly elevated in all septic dogs in which it was measured. The free concentrations of amino acids in the liver, heart, and muscle tissues were grossly elevated in the low intravenous alimented septic state relative to the fasted normal state, whereas the tissue concentrative ability as measured by nonmetabolizable amino acids, alpha-aminoisobutyrate and cycloleucine, was not similarly increased. Sepsis clearly alters plasma and tissue concentrations, and in some instances hepatic uptake of amino acids.
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PMID:Plasma concentrations and tissue uptake of free amino acids in dogs in sepsis and starvation: effects of glucose infusion--some effects of low alimentation. 65 52

Major thermal injury is associated with extreme hypermetabolism and catabolism as the principal metabolic manifestations encountered following successful resuscitation from the shock phase of the burn injury. Substrate and hormonal measurements, indirect calorimetry, and nitrogen balance are biochemical metabolic parameters which are useful and more readily available biochemical parameters worthy of serial assessment for the metabolic management of burn patients. However, the application of stable isotopes with gas chromatography/mass spectroscopy and more recently, new immunoassays for growth factors and cytokines has increased our understanding of the metabolic manifestations of severe trauma. The metabolic response to injury in burn patients is biphasic wherein the initial ebb phase is followed by a hypermetabolic and catabolic flow phase of injury. The increased oxygen consumption/metabolic rate is in part fuelled by evaporative heat loss from wounds of trauma victims, but likely also by a direct central effect of inflammation upon the hypothalamus. Although carbohydrates in the form of glucose appear to be an important fuel source following injury, a maximum of 5-6 mg/kg/min only is beneficial. Burn patients have accelerated gluconeogenesis, glucose oxidation, and plasma clearance of glucose. Additionally, considerable futile cycling of carbohydrate intermediates occurs which includes anaerobic lactate metabolism and Cori cycle activity arising from wound metabolism of glucose and other substrates. Similarly, accelerated lipolysis and futile fatty acid cycling occurs following burn injury. However, recent evidence suggests that lipids in the diet of burned and other injured patients serve not only as an energy source, but also as an important immunomodulator of prostaglandin metabolism and other immune responses. Amino acid metabolism in burn patients is characterized by increased oxidation, urea synthesis, and protein breakdown which is prolonged and difficult to reduce with current nutritional therapy. However, the current goal of nutritional support is to optimize protein synthesis. Specific unique requirements may exist for supplemental glutamine and arginine following burn injury but further research is needed before enhanced branched chain amino acids supplements can be recommended for burn patients. Recent research investigations have revealed the importance of enteral feeding to enhance mucosal defense against gut bacteria and endotoxin. Similarly, research has demonstrated that many of the metabolic perturbations of burns and sepsis may be due, at least in part, to inflammatory cytokines. Investigation of their pathogenesis and mechanism of action both at a tissue and a cellular level offer important prospects for improved understanding and therapeutic control of the metabolic disorders of burn patients.
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PMID:The metabolic effects of thermal injury. 129 Feb 69

1. The effects of parenteral nutrition with or without glutamine supplementation and epidermal growth factor treatment (0.15 microgram/g body weight) was studied in the small bowel of septic rats after 4 days. 2. Septic rats infused with glutamine-supplemented parenteral nutrition with or without epidermal growth factor treatment survived sepsis significantly better than other septic rats given parenteral nutrition. The cumulative percentage of deaths over 4 days in septic rats infused with glutamine-supplemented parenteral nutrition was 20% (without epidermal growth factor) and 15% (with epidermal growth factor) compared with 50% in septic rats treated with parenteral nutrition without glutamine and 35% in septic rats given parenteral nutrition without glutamine but with epidermal growth factor treatment. 3. Glutamine-supplemented parenteral nutrition with or without epidermal growth factor treatment resulted in improved nitrogen balance in septic rats. The cumulative nitrogen balance over the 4 day period was the least negative as compared with other groups of septic rats. 4. Septic rats given parenteral nutrition with glutamine, epidermal growth factor or glutamine and epidermal growth factor exhibited marked increases in intestinal net rates of utilization of glutamine (P less than 0.001) and production of ammonia (P less than 0.001) compared with septic rats given parenteral nutrition without glutamine and/or epidermal growth factor treatment. 5. Septic rats given parenteral nutrition with glutamine, epidermal growth factor or glutamine and epidermal growth factor exhibited significant increases in jejunal wet weight (by 32.4-40.6%), DNA content (by 24.2-34.7%), protein content (by 29.1-50.0%), villus height (by 16.3-26.4%) and crypt depth (by 20.3-29.6%) compared with other groups of septic rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of epidermal growth factor and glutamine-supplemented parenteral nutrition on the small bowel of septic rats. 131 68

The effects of a single dose of endotoxin (7.5 mg/kg BW) on skeletal muscle glutamine metabolism were studied in vivo in rats to gain further understanding of the altered glutamine metabolism that characterizes sepsis and other catabolic diseases. In endotoxin-treated animals the arterial glutamine concentration fell early initially and then increased compared with control values. Twelve hours after treatment, the arteriovenous concentration difference for glutamine across the hindquarter doubled, resulting in a significant increase in net muscle glutamine release in endotoxin-treated rats. As a consequence, the muscle glutamine concentration fell in the endotoxin-treated animals by 25%-40%, an event that was apparent as early as two hours after endotoxin treatment. Skeletal muscle glutaminase activity, the major enzyme of glutamine breakdown, was unchanged by endotoxemia, but expression of glutamine synthetase mRNA and glutamine synthetase specific activity increased in a time-dependent fashion. The glutamine depletion that develops in skeletal muscle during endotoxemia is caused by accelerated muscle glutamine release rather than an increase in intracellular degradation or a fall in intracellular biosynthesis. The adaptive increase in glutamine synthetase expression that occurs requires de novo RNA and protein synthesis and may be designed to prevent complete depletion of the intracellular glutamine pool.
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PMID:Adaptive regulation in skeletal muscle glutamine metabolism in endotoxin-treated rats. 135 Mar 13

1. The effects of parenteral nutrition with or without xylitol and/or glutamine supplementation were studied in septic rats after 4 days of treatment. 2. Septic rats treated with xylitol- and/or glutamine-supplemented parenteral nutrition survived sepsis significantly better than other parenteral nutrition-treated septic rats: the cumulative percentage of deaths over 4 days in septic rats treated with xylitol-glutamine-supplemented parenteral nutrition was 9.5% compared with 54.5% in septic rats given parenteral nutrition without xylitol and glutamine, and 52.4% in septic rats treated with parenteral nutrition supplemented with glucose. 3. Xylitol- and/or glutamine-supplemented parenteral nutrition resulted in improved nitrogen balance in septic rats: the cumulative nitrogen balance over the 4 days of treatment was positive in the rats given xylitol-supplemented parenteral nutrition and more positive when rats were treated with xylitol-glutamine-supplemented parenteral nutrition, 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 xylitol- and/or glutamine-supplemented parenteral nutrition in septic rats. 5. Hepatic protein and RNA contents were increased in septic rats treated with xylitol- and/or glutamine-supplemented parenteral nutrition. Similarly, protein and RNA contents were markedly increased in muscles of septic rats treated with xylitol- and/or glutamine-supplemented parenteral nutrition. 6. The rates of incorporation of leucine/tyrosine into liver/muscle proteins in vitro were increased and the rate of muscular tyrosine release was decreased in response to xylitol- and/or glutamine-supplemented parenteral nutrition in septic rats. 7. It is concluded that the administration of xylitol- and/or glutamine-supplemented parenteral nutrition is beneficial to septic rats and possibly to septic patients.
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PMID:Effects of xylitol- and/or glutamine-supplemented parenteral nutrition on septic rats. 137 1

1. The hepatic metabolism of glutamine, alanine, ammonia, urea, glutathione and glucose was studied in rats made septic by caecal ligation and puncture and was compared with that in rats that had undergone sham operation (laparotomy). 2. Sepsis resulted in increases in the plasma activities of gamma-glutamyltransferase (P less than 0.001), alanine aminotransferase (P less than 0.001) and aspartate aminotransferase (P less than 0.001), the serum total and direct bilirubin concentrations (P less than 0.001), and the blood lactate (P less than 0.01), glutamine (P less than 0.05), alanine (P less than 0.001) and urea (P less than 0.05) concentrations, but produced decreases in the blood ketone body (P less than 0.001) and glutathione (P less than 0.05) concentrations and in the plasma cholesterol concentration (P less than 0.05). These changes were associated with marked negative nitrogen balance in septic rats. 3. Sepsis increased total hepatic blood flow (by 22.7%) together with hepatic arterial flow (by 25.8%) and portal venous flow (by 18.7%). Sepsis resulted in marked increases in the net rates of hepatic extraction of glutamine (by 164%), alanine (by 138%) and ammonia (by 259%) with concomitant increases in the net rates of hepatic release of glutamate (by 105%), glutathione (by 87.5%), glucose (by 70.1%) and urea (by 100.4%). 4. Sepsis increased the activities of liver carbamoylphosphate synthase (by 16.4%), ornithine transcarbamylase (by 29.8%), argininosuccinate synthase (by 28.1%) and arginase (by 33.8%). 5. Septic rats exhibited marked increases in hepatic protein (by 46.0%), RNA (by 43.4%) and DNA (by 37.7%) contents. These changes were accompanied by marked increases in the activity of thymidine kinase (by 35.9%).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hepatic glutamine metabolism in the septic rat. 137 98

The effects of glutamine concentration on the phagocytosis of an opsonized antigen, the synthesis of RNA, and the production of interleukin-1 (IL-1) by macrophages were investigated in vitro. A minimum A minimum of 0.125 mmol/L glutamine was required for a significant increase in phagocytosis of opsonized sheep erythrocytes, compared with that recorded for macrophages cultured in the absence of glutamine. The synthesis of 3H-RNA by macrophages also required 0.125 mmol/L glutamine in the culture medium before it was significantly increased above the levels of control cultures. A minimum of 0.03 mmol/L glutamine was required for the induction of significant levels of IL-1 by lipopolysaccharide (LPS)-stimulated macrophages. Therefore, recent findings suggesting that decreases in plasma glutamine resulting from major burn injury, sepsis, trauma, and surgery may be partly responsible for the associated impairment of immune function now have a basis in both phagocytosis and in modulation of the synthesis of IL-1 (the first cytokine of the interleukin cascade that leads to specific immunity) by macrophages, in addition to the previously established dependency of lymphocytes on external sources of glutamine for their replication.
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PMID:Glutamine and macrophage function. 138 59

This study was carried out to elucidate the protein and amino acids metabolism in septic rats, using constant infusion of 1-13C-leucine (4mg/hr), 5-13C-glutamine (2mg/hr), 1,2-13C-leucine (4mg/hr), or U-14C-leucine (2.0uCui/hr). Whole body protein kinetics showed that protein breakdown rate was increased in sepsis, but no change was found on protein synthesis rate (PSR). Intestinal mucosal fractional synthesis rate (FSR) was increased with sepsis. However, sepsis caused significant decrease of muscle FSR. Both leucine and glutamine oxidation rates were significantly increased in sepsis. Fraction of leucine degradation via glutamine was significantly increased in sepsis. We concluded that 1) both leucine and glutamine were utilized as important energy fuels in sepsis, 2) whole body PSR was influenced by the change of PSR in each organ, 3) the pathway from leucine to glutamine was significant in the degradation of leucine.
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PMID:[Protein turnover and amino acids metabolism in septic rats]. 144 42

Recent investigations from our and other laboratories indicate that glycogen is a carbon-chain precursor in muscle for the synthesis of TCA cycle intermediates and glutamine. During intense exercise and in conditions of a relative lack of energy (hypoxia, trauma, sepsis) the metabolism of branched-chain amino acids (BCAA) is accelerated in muscle. In the primary BCAA aminotransferase reaction 2-oxoglutarate is used as amino-group acceptor (putting a carbon-drain on the TCA cycle) under formation of glutamate. Glutamate will subsequently react with ammonia, generated in the AMP deaminase reaction or by deamination of amino acids, under formation of glutamine in a reaction catalysed by glutamine synthetase (glutamate + ammonia + ATP--> glutamine + ADP). Muscle glycogen stores may be smaller or less available at high altitude. It is hypothesized that this will lead to premature fatigue (due to both a lack of fuel and of TCA cycle carbon-precursor) and to a reduction in the synthesis rate of glutamine. A chronic reduction in the synthesis rate of glutamine during a long term stay at high altitude on its turn may lead to gut atrophy, bacterial translocation, endotoxemia, muscle protein catabolism and a weakened immune status.
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PMID:Amino acid metabolism, muscular fatigue and muscle wasting. Speculations on adaptations at high altitude. 148 45

Conceptualization of the gastrointestinal tract as the "motor" that drives sepsis and multiple-system organ failure has only recently been appreciated. Most of the investigation into the pathophysiology of gut-derived sepsis involves using animal models; however, some of the findings are already being corroborated in human studies. The gastrointestinal tract is a dynamic organ whose function as a front-line defense against infection needs to be appreciated. The development of lethal sepsis is a function of the microbial load and virulence, the status of the gastrointestinal barrier, and the magnitude of the host defense response. In assuming care of a critically ill patient, we must be judicious in the use of antibiotics in order to prevent intestinal overgrowth of potential pathogens. Providing proper nutrition by an enteral route (when possible) not only satisfies caloric needs but regulates the microflora and maintains the integrity of the mucosal barrier. Burn patients should receive enteral nutrition early, the first day if possible. This not only will protect the intestinal mucosa but also will blunt the hypermetabolic response following thermal injury. Lastly, the patient should not receive an excessive amount of narcotic or sedative, for these drugs have an inhibitory effect on gastrointestinal motility, encouraging bacterial overgrowth. In the near future, new therapeutic modalities may soon become available to protect and treat the compromised gastrointestinal barrier. These modalities may include, but certainly are not limited to, the use of glutamine and xanthine oxidase inhibitors to prevent stress-related injury to the gastrointestinal mucosa.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The role of the gastrointestinal tract in the development of burn sepsis. 151 4


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