Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The effect of sepsis, induced by caecal ligation plus puncture (CLP) or endotoxin injection, on glutamine metabolism was studied in rat skeletal muscle. 2. The concentration of glutamine in muscle was decreased by CLP or after 24 or 48 hr after injection of endotoxin. However, the concentration was increased 3 hr after injection of endotoxin. 3. The plasma glutamine concentration was decreased by CLP, but it was unchanged after injection of endotoxin. 4. The rate of glutamine release from incubated stripped soleus muscles was increased in the muscles removed from animals subjected to CLP or from animals injected with endotoxin. 5. It is concluded that sepsis results in marked changes in skeletal muscle glutamine metabolism, which may be used as an early indicator of the septic state. During sepsis there is likely to be an increased demand for glutamine by the immune system, kidney and intestine. 6. This study provides evidence that during sepsis the rate of release of glutamine from the skeletal muscle per se is increased to a sufficient extent to satisfy this increased requirement.
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PMID:Skeletal muscle glutamine metabolism during sepsis in the rat. 274 10

A carrier for glutamine, identified in rat muscle, has properties in terms of kinetics, ion dependence and hormone sensitivity, and effects of endotoxin and branched-chain aminoacids that point to an important function in the control of whole-body aminoacid metabolism. The existence of a link between the size of the glutamine pool in muscle and the rate of muscle protein synthesis raises possibilities for therapeutic interventions to limit protein loss in injury, sepsis, and chronic disease.
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PMID:Characteristics of a glutamine carrier in skeletal muscle have important consequences for nitrogen loss in injury, infection, and chronic disease. 287 74

An infant with the acute neonatal form of pyruvate carboxylase deficiency (cross-reacting material negative) presented with severe intractable lactic acidosis within 4 h after birth. He also had hyperammonemia, hypercitrullinemia, and hyperlysinemia. Plasma glutamine was not elevated. He had a rapidly deteriorating clinical course with severe liver dysfunction, repeated septicemia and seizures; he was comatose and was on a ventilator throughout; death occurred at 8 wk of age. Skin fibroblast study confirmed the enzyme deficiency. Detailed biochemical parameters and histopathology of the brain and liver are presented. The evidence from this infant suggests that disturbances of intracellular oxaloacetate levels as a result of the primary enzyme defect might also contribute to deficiency in ATP generation which may explain the various other biochemical changes and liver pathology.
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PMID:Biochemical and histologic pathology in an infant with cross-reacting material (negative) pyruvate carboxylase deficiency. 308 60

We investigated the influence of leupeptin (LP) intraperitoneal injection (40 mumol/2 days) on protein and amino-acid metabolism of septic rats (cecal ligation). All septic rats lost weight (-17 +/- 4 g), which was not prevented by LP administration (-24 +/- 1.8 g, n.s.). LP injection evoked weight loss even in normal rats (p less than 0.05 vs controls). Weight loss was accompanied by enhanced urinary nitrogen losses in all three groups. LP reduced food intake for 47% in control rats. Cecal ligation, and also the administration of LP, led to alterations of amino-acid metabolism. The most important changes were found in muscle free amino-acid concentrations with highly decreased levels of free glutamine. A glutamine deficiency is known to be related to a decreased rate of protein synthesis. The proteolytic rate in incubated soleus muscle was increased for 11.5% and even higher in LP-treated septic rats (+22%). It is concluded that the administration of LP cannot reverse protein catabolism in sepsis--possibly because LP does not influence those enzymes or proteases involved in tissue loss, or LP is inactivated by enzymes in rat tissues.
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PMID:Influence of leupeptin on protein and amino-acid metabolism in septic rats. 320 62

The time course (12, 24 and 48 h) of changes in blood metabolites, and in gluconeogenesis and ketogenesis, in isolated hepatocytes from rats made septic by caecal ligation and puncture was measured. Blood glucose was not significantly different in septic rats, but lactate was increased at 12, 24 and 48 h; pyruvate and alanine were increased at 48 h. The blood ketone body concentrations were decreased at all times studied after induction of sepsis. These changes were accompanied by increased plasma insulin in the septic rats. The rate of hepatic lipogenesis in vivo was increased at 24 and 48 h. There were appreciable increases in the hepatic concentrations of alanine (200%), lactate (200%) and pyruvate (100%) as well as other intermediates in the gluconeogenic pathway. The hepatic concentrations of acetyl-CoA and ketone bodies were decreased. The rate of gluconeogenesis from added lactate, pyruvate, alanine and glutamine was depressed in isolated hepatocytes from septic rats at 24 and 48 h. The basal rate of ketogenesis or the rate from butyrate in isolated hepatocytes was not significantly altered by sepsis, whereas the rate from oleate was decreased at all time points. It is concluded that there is an impairment of the capacity for gluconeogenesis and ketogenesis in livers of septic rats. The latter may be due to decreased entry of long-chain acyl-CoA into the mitochondria for oxidation. The possibility that these changes are in part brought about by the hyperinsulinaemia associated with the sepsis is discussed.
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PMID:Time course of changes in hepatic metabolism in response to sepsis in the rat: impairment of gluconeogenesis and ketogenesis in vitro. 329 69

Many aspects of the cell biology of lymphocytes and macrophages have been studied extensively over many years. Our recent work on these cells has investigated the fuels utilized, the metabolism carried out and the importance of this metabolism for the specific function of these cells in the immune system. The quantitatively important role of glutamine and the observation that both glutamine and glucose are only partially oxidized by both types of cell have been established. This work has led to a new hypothesis to explain the high rates of partial oxidation of both fuels in lymphocytes and macrophages, and in other cells such as enterocytes, colonocytes and also in neoplastic cells. In addition, the high rate of glutamine utilization and its importance in such cells has raised the question as to the source of this glutamine in the body: the evidence suggests that this is muscle. The metabolic relationship between the glutamine-producing tissue and the cells of the immune system provides an explanation for some well-established changes in metabolism during the condition of surgery, trauma, sepsis and burns. Knowledge of the metabolism of glucose, glutamine, pyruvate and long-chain fatty acids by these cells raises some intriguing questions concerning the role and function of the citric acid cycle in these and other similar cells, including tumour cells.
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PMID:The role of the citric acid cycle in cells of the immune system and its importance in sepsis, trauma and burns. 333 91

To examine alterations in amino acid metabolism after trauma and sepsis, male Sprague-Dawley rats underwent no operation (control, CON), celiotomy (trauma, TRA), or cecal ligation and puncture (sepsis, CLP). After 16 hr, plasma amino acid concentrations were determined. A second group of similarly prepared animals underwent isolated liver perfusion, and net amino acid uptake or release was determined over 30 min. Sepsis significantly decreased total amino acid concentration in portal plasma (CON, 3486 +/- 156 nmole/ml; TRA, 3407 +/- 150 nmole/ml; CLP, 2738 +/- 148 nmole/ml). Glutamine concentrations were uniformly lower in portal plasma than in arterial plasma in all states. There were depressed concentrations of the branched chain amino acids (BCAA) in portal plasma after trauma but not sepsis. In the isolated liver perfusion model, a marked increase in amino acid uptake was induced by sepsis (CON, 39.9 +/- 7.9 mumol/g liver protein; TRA, 49.5 +/- 17.3 mumol/g liver protein; CLP, 124 +/- 11 mumol/g liver protein). In addition, there was significantly greater uptake of threonine, asparagine, proline, methionine, tyrosine, and arginine. Although the BCAA isoleucine and valine were taken up to a greater extent in sepsis, the overall BCAA uptake was not significantly greater in sepsis than in control (CON 6.92 +/- 2.15 mumol/g liver protein vs CLP 15.8 +/- 1.9 mumol/g liver protein). The greatest increase in uptake following sepsis was among the gluconeogenic precursor amino acids alanine, glycine, threonine, and serine (CON, 27.0 +/- 4.2 mumol/g liver protein, TRA, 38.8 +/- 8.9 mumol/g liver protein; CLP, 62.8 +/- 6.0 mumol/g liver protein).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Amino acid uptake in isolated, perfused liver: effect of trauma and sepsis. 339 92

The determination of free amino acids (AA) in human tissue is far more complicated than the analysis of plasma AA. The concentrations of free AA are different in plasma, liver and muscle, respectively. Pathological conditions like sepsis, liver failure and glucagonoma syndrome lead to characteristic alterations in the concentrations of free AA. However, the relationship between cytosolic AA concentrations and protein synthesis are not yet clear. Possibly drastically reduced levels of single AA (e.g. glutamine) lead to a 'down'-regulation of protein synthesis.
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PMID:[Intracellular amino acid concentrations in various disease states]. 367 18

The effect of dexamethasone sodium phosphate on visceral organ glucose metabolism was studied in order to gain further understanding of the altered glucose dynamics that occur following catabolic states. Glucose, glutamine, and alanine exchange across the gastrointestinal (GI) tract, liver, and kidneys was determined in 25 awake dogs that were catheterized on a long-term basis during a control period and after dexamethasone sodium phosphate treatment (0.44 mg/kg/day) for two (dexamethasone 2) and nine (dexamethasone 9) days. The GI tract consumed glucose in control dogs but switched to an organ of balance or slight release with dexamethasone. Simultaneously, gut glutamine consumption increased markedly, as did intestinal alanine release. Hepatic glucose production more than doubled with dexamethasone at a time when hepatic alanine uptake was greatly increased. The kidneys demonstrated glucose balance in control animals, but released glucose with dexamethasone 9. The gut and kidneys may play an important role in the altered glucose dynamics seen in patients with sepsis and other catabolic diseases.
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PMID:Gut-liver interaction during accelerated gluconeogenesis. 383 33

To investigate the metabolic effects of interleukin-1 and its role as a mediator of host responses to trauma and sepsis, we injected seven healthy male subjects with etiocholanolone, an inflammatory agent that stimulates systemic responses thought to be mediated by interleukin-1. The subjects were fed a constant diet during each 4-day study and received three daily intramuscular injections of etiocholanolone, 0.10 mg/kg. Etiocholanolone injection resulted in inflammation, fever, leukocytosis, increased serum C-reactive protein, hypoferremia, and increased plasma activity of interleukin-1/lymphocyte-activating factor. Plasma concentrations of the counterregulatory hormones were normal. Protein metabolism, as reflected in nitrogen balance, 15N turnover, and forearm flux of alanine and glutamine, was unaltered. Serum glucose and insulin levels and tissue responsiveness to insulin were normal. This dissociation of acute-phase and catabolic responses may reflect the magnitude of the stimulus; higher levels of interleukin-1 may initiate catabolic responses. Alternatively, other mediators such as the counterregulatory hormones may direct the catabolic responses that occur after injury and sepsis.
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PMID:The induction of interleukin-1 in humans and its metabolic effects. 389 42


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