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

This study examined the relationship between elevation of blood phenylalanine (Phe) concentrations often observed in trauma or infected patients without hepatic dysfunction and alterations of liver Phe catabolism. Rats underwent pathophysiologically different stresses, either sepsis or scald injury. The catalytic activity of hepatic Phe hydroxylase (PH) in the septic rats, as measured after preincubation with Phe, decreased to 60% of the control values; this in vitro result suggests a reduction of enzyme species activated by its substrate. Phe was degraded in the septic rats to a similar extent to that in controls, when measured by pulse administration of [1-14C]-Phe. In the scalded rats whose plasma Phe level showed a comparable but transient increase, no significant alterations occurred in Phe catabolism and enzyme activities. The changes in plasma glucagon and catecholamine levels were consistent with those of the enzyme activities involved in Phe and tyrosine (Tyr) catabolism in the stressed groups. These results indicate that inadequate activation of native PH by regulatory mechanisms involving Phe in vivo was also associated with the accumulation of plasma Phe in infected rats during massive mobilization of amino acids from muscles under conditions of enhanced and sustained catabolism.
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PMID:Alterations in levels of plasma phenylalanine and its catabolism in the liver of stressed rats. 164 Aug 56

The metabolism of skeletal muscle glutamine was studied in rats made septic by cecal ligation and puncture technique. Blood glucose was not significantly different in septic rats, but lactate, pyruvate, glutamine, and alanine were markedly increased. Conversely, blood ketone body concentrations were markedly decreased in septic rats. Both plasma insulin and glucagon were markedly elevated in septic rats. Sepsis increased the rates of glutamine production in muscle, but without marked effects on skin and adipose tissue preparations, with muscle production accounting for over 87% of total glutamine produced by the hindlimb. Sepsis produced decreases in the concentrations of skeletal muscle glutamine, glutamate, 2-oxoglutarate, and adenosine monophosphate (AMP). The concentrations of ammonia, pyruvate, and inosine monophosphate (IMP) were increased. Hindlimb blood flow showed no marked change in response to sepsis, but was accompanied by an enhanced net release of glutamine and alanine. The maximal activity of glutamine synthetase was increased only in quadriceps muscles of septic rats, whereas that of glutaminase was decreased in all muscles studied. Tyrosine release from incubated muscle preparation was markedly increased in septic rats; however, its rate of incorporation was markedly decreased. It is concluded that there is an enhanced rate of production of glutamine from skeletal muscle of septic rats. This may be due to changes in efflux and/or increased intracellular formation of glutamine; these suggestions are discussed.
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PMID:Glutamine metabolism in skeletal muscle of septic rats. 167 Nov 65

1. The metabolism of glutamine and alanine in the lung was studied in rats made septic by a caecal ligation and puncture technique. 2. The blood glucose concentration was not significantly different in septic rats, but blood pyruvate, lactate, glutamine and alanine concentrations were markedly increased as compared with sham-operated rats. Conversely, blood ketone body and plasma cholesterol concentrations were significantly decreased in septic rats. Both plasma insulin and plasma glucagon concentrations were markedly elevated in response to sepsis. Sepsis resulted in a negative nitrogen balance. 3. Sepsis increased the rates of production of glutamine (52.5%, P less than 0.001), alanine (38.9%, P less than 0.001) and glutamate (48.6%, P less than 0.001) by lung slices incubated in vitro. 4. Sepsis increased lung blood flow by 27.6% (P less than 0.05). Blood flow and arteriovenous concentration difference measurement across the lung of septic rats showed an increase in the net exchange rates of glutamine (142.5%, P less than 0.001), alanine (129.4%, P less than 0.001), glutamate (100.9%, P less than 0.001) and ammonia (138.0%, P less than 0.001) as compared with sham-operated control rats. 5. Sepsis produced significant decreases in the lung concentrations of glutamine (36.8%), glutamate (20.8%), 2-oxoglutarate (64.8%) and AMP (18.3%). The lung concentrations of alanine (95.9%), ammonia (67.7%) and pyruvate (89.7%) were increased. 6. The maximal activities of glutamine synthetase (20.4%, P less than 0.05), phosphate-dependent glutaminase (18.9%, P less than 0.05) and alanine aminotransferase (25.5%, P less than 0.05) were increased, but there was no marked change in that of glutamate dehydrogenase, in the lungs of septic rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glutamine and alanine metabolism in lungs of septic rats. 168 36

Immunological implications are important in every surgical operation, specially when it is necessary to remove the spleen. She plays an important role in immunological aspecific (filter, phagocytosis) and specific processes (production of IgM and regulation of T- and B-lymphocytic system). Splenectomy causes an immunodeficiency with frequent post-operative complications (the most important is OPSI). Each operated patient is considered generically immunodeficient because surgical trauma and anesthesiologic practice are at the base of immunological alterations (biological barriers, aspecific immunity, A.P.P., complement, specific immunity, NK cells). It's indispensable to know pathological situations that make "critical" the immunological state: caloric-proteic malnutrition, elderly (greater than 70 years old), immunosuppressive therapy, sepsis, shock, neoplasms. I. e.: a patient about seventy years old presents a reduced endocrine secretion of thymic hormone and, probably, a low synthesis of immunoglobulins. Besides the corticosteroids modify the answer of T-lymphocytes and NK cells. Sepsis induces metabolic and immunological alterations after early activation of humoral mediators, modified quantity and life of A.P.P., activation of complement, inhibition of cell-mediate immunity, modification of number and activity of haematic lymphocytes. Trauma induces a hypersecretion of corticosteroid, adrenalin, noradrenaline, glucagon with consequent hypercatabolism that causes malnutrition. The hormonal hypersecretion is a determining factor of reduced phagocytic activity (inhibited migration of neutrophils and monocytes), quantitative and qualitative alterations of complement, deficit of T-cells, hyporeactivity to skin test, depressed answer of antibodies to bacterial and viral antigens. Progressive neoplasms are characterized by modification of T-lymphocytes number, depressed macrophagic activity, hyporeactivity to skin tests.
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PMID:[Immunological implications of surgical intervention in critical and noncritical patients]. 175 43

1. In sepsis various processes of carbohydrate metabolism, such as hepatic gluconeogenesis and glycolysis, are altered. Phosphofructokinase-1, a key glycolytic enzyme, is controlled in the long term via regulation of synthesis and degradation of the protein itself, while in the short term it is regulated by allosteric effectors, such as fructose 2,6-bisphosphate (the most potent). In the present study hepatic phosphofructokinase-1 activity as well as phosphofructokinase-2 activity and the concentration of fructose 2,6-bisphosphate were assayed to determine if they might contribute to the derangement of carbohydrate metabolism seen commonly in sepsis. 2. The levels of glycogen and fructose 2,6-bisphosphate and the activity of phosphofructokinase-1 and phosphofructokinase-2 were determined in hepatic biopsies obtained at laparotomy from six patients with and seven patients without abdominal septic foci. 3. A significant increase in plasma lactate concentration was observed in the septic patients, whereas no significant differences in tissue glycogen content or plasma glucose concentration were seen between the groups. 4. No significant change in plasma insulin concentration was observed. However, levels of the counter-regulatory hormones (glucagon, cortisol and adrenaline) were elevated in the septic patients. 5. A 60% decrease in hepatic phosphofructokinase-1 activity was seen in the septic patients. However, no significant changes in hepatic phosphofructokinase-2 activity and fructose 2,6-bisphosphate content were observed in the septic patients. 6. The present results demonstrate that the decrease in hepatic phosphofructokinase-1 activity occurring in sepsis does not appear to reflect alterations in the concentration of fructose 2,6-bisphosphate.
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PMID:Hepatic phosphofructokinase-1 activity and fructose 2,6-bisphosphate levels in patients with abdominal sepsis. 185 Jun 80

The hepatic toxicity of TPN that is seen clinically appears to be multifactorial in origin. Most patients develop a combination of hepatic steatosis with evidence of cholestasis and abnormalities in liver function. The model that we have studied is one of pure hepatic steatosis since, on repeated study, these rats do not develop any liver function abnormalities. It is unclear whether this is related to the fact that these are short-term experiments, that rat livers respond differently from humans, or that rats do not have gallbladders. It has not been possible to carry these experiments out beyond 3 weeks since the rats develop bacterial colonization of the central lines as well as evidence of line sepsis. thus confounding the issue of hepatic toxicity being due to the TPN or to sepsis. One hypothesis is that hepatic steatosis is an early marker of liver toxicity and that prevention or reversal of hepatic steatosis may protect the liver from further abnormality. Insulin and glucagon seem to play a critical role in the development of TPN-associated hepatic steatosis. Specifically, an elevated portal venous insulin-glucagon molar ratio appears to be the primary stimulus and any treatment that lowers this ratio should diminish hepatic steatosis. The use of glucagon as a treatment modality is new. We have found no evident side effects of low dose glucagon in rats when it is added to the TPN solution. Glutamine has received much attention recently as a nutritional pharmacological agent in ameliorating some of the intestinal complications of parenteral nutrition and is well tolerated when administered appropriately. Intravenous lipid administration is an important nonprotein calorie source, especially when a high dextrose base cannot be used, and plays a role as well in preventing the development of hepatic steatosis. Thus, it is suggested that the clinical treatment of hepatic steatosis during TPN can be safely performed using any one, or a combination, of these modalities and without having to discontinue the TPN infusions. Since we observed no deterioration of liver function in rats receiving TPN for up to 2 weeks, we cannot completely relate these findings and recommendations to the hepatic dysfunction seen clinically with the use of TPN. Additional study will be required before this can be conclusively determined.
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PMID:Pathogenesis of hepatic steatosis during total parenteral nutrition. 190 28

Tumor Necrosis Factor (TNF) has been implicated in the early metabolic events following acute tissue injury or sepsis; it increases blood levels of glucocorticoids and glucagon or the cellular responses to the hormones. To examine whether stress-related hormones have any effect on macrophage activation by TNF, human monocyte-derived macrophages were exposed to somatostatin (S), ACTH, angiotensin (An), insulin (I), epinephrine (E), and glucagon (G) at physiologic concentrations. 125I-TNF binding as well as the ability of TNF to activate macrophages to kill an intracellular pathogen (Mycobacterium avium) were measured. While treatment with recombinant interferon gamma increased the number of TNF receptors by 53 +/- 8%, E, I, G, S, ACTH and An decreased the number of receptors by 81 +/- 6%, 83 +/- 6%, 15 +/- 5%, 83 +/- 4%, 17 +/- 4% and 21 +/- 4%, respectively. Treatment with I, E, and S also decreased the ability of macrophages to kill M. avium by 30 +/- 1%, 20 +/- 6%, and 51 +/- 2%, respectively. These in vitro results suggest that stress hormones influence TNF-mediated activation of macrophages.
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PMID:Effect of stress-related hormones on macrophage receptors and response to tumor necrosis factor. 197 Oct 32

Epinephrine produces smaller incremental increases in plasma glucose concentration and rate of glucose appearance (Ra) in septic rats compared with nonseptic animals. In the present study, we investigated the role of insulin in the diminished response of septic rats to epinephrine-induced increases in glucose turnover. Glucose kinetics were assessed by the infusion of [6-3H]-glucose in conscious catheterized rats made septic by subcutaneous injections of live Escherichia coli. Epinephrine was infused at 1 micrograms/min/kg for 2 hours in the presence and absence of somatostatin and mannoheptulose (SRIF + MH). In comparison to nonseptic control animals, epinephrine-induced increases in plasma glucose concentration and glucose Ra were blunted by more than 50% in the septic rats. Infusion of SRIF + MH with epinephrine restored the blunted response to normal. During the infusion of epinephrine alone, the plasma insulin concentration in the septic rats was 2.8-fold higher than the nonseptic controls. SRIF + MH lowered the plasma insulin concentrations in both the nonseptic and septic rats to less than 10 microU/mL. SRIF + MH reversed the sepsis-induced hyperglucagonemia, but did not prevent a slight increase in glucagon levels during the epinephrine infusion in the nonseptic rats. In a second study, septic rats infused with SRIF + MH and replacement insulin showed a smaller increase in glucose concentration and glucose production in response to epinephrine than did septic animals administered SRIF + MH and no insulin. These results indicate that insulin plays an important role in the diminished response of septic rats to epinephrine.
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PMID:Role of insulin in the blunted glucose metabolic response of septic rats to epinephrine. 197 24

The activity of phosphate-dependent glutaminase and glutamine metabolism by tissues known markedly to utilize or synthesize glutamine (or both) were studied in rats made septic by cecal ligation and puncture technique and compared with the same measures in rats that underwent sham operation (laparotomy). Blood glucose level was not markedly different in septic rats, but lactate, pyruvate, alanine, and glutamine levels were markedly increased. Conversely, blood ketone body concentrations were significantly decreased in septic rats. Both plasma insulin and glucagon levels were markedly elevated in response to sepsis. The maximal activity of phosphate-dependent glutaminase was decreased in the small intestine, increased in the kidney and mesenteric lymph nodes, and unchanged in the liver of septic rats. Arteriovenous concentration difference measurements across the gut showed a decrease in the net glutamine removed from the circulation in septic rats. Arteriovenous concentration difference measurements for glutamine showed that both renal uptake and skeletal muscle release of the amino acid were increased in response to sepsis, whereas measurements across the hepatic bed showed a net uptake of glutamine in septic rats. Enterocytes isolated from septic rats exhibited a decreased rate of utilization of glutamine and production of glutamate, alanine, and ammonia, whereas lymphocytes isolated from septic rats showed an enhanced rate of utilization of glutamine and production of glutamate, aspartate, and ammonia. It is concluded that, during sepsis, glutamine uptake and metabolism are enhanced in renal and lymphoid tissue but decreased in that of the small intestine, with increased rates of release by skeletal muscle; however, the liver appears to utilize glutamine in septic rats.
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PMID:Maximal activity of phosphate-dependent glutaminase and glutamine metabolism in septic rats. 206 39

1. The regulation of renal gluconeogenesis was studied in rats made septic by a caecal ligation and puncture technique. 2. Blood glucose concentrations were not markedly different in septic rats, but lactate, pyruvate and alanine concentrations were markedly increased, compared with sham-operated rats. Conversely, blood ketone body concentrations were significantly decreased in septic rats. Both plasma insulin and glucagon concentrations were markedly elevated in response to sepsis. 3. The maximal activities of glucose-6-phosphatase (EC 3.1.3.9), fructose-1,6-bisphosphatase (EC 3.1.3.11), pyruvate carboxylase (EC 6.4.1.1) and phosphoenolpyruvate carboxykinase (EC 4.1.1.49) were markedly decreased in kidneys obtained from septic rats, suggesting diminished renal gluconeogenesis. 4. Renal concentrations of lactate, pyruvate and other gluconeogenetic intermediates were markedly elevated in septic rats, whereas those of acetyl-CoA and fructose 2,6-bisphosphate were decreased and unchanged, respectively. 5. The rate of gluconeogenesis from added lactate, pyruvate and glycerol was decreased in isolated incubated renal tubules from septic rats. 6. Sepsis decreased the arteriovenous concentration difference for glucose, lactate, and alanine. Septic rats showed decreased net rates of glucose production and net rates of removal of lactate and alanine as compared with sham-operated controls. 7. It is concluded that the diminished capacity for renal gluconeogenesis in septic rats could be the result of changes in the maximal activities or regulation of key non-equilibrium gluconeogenic enzymes or both, but the effect of other factors (e.g. toxins) has not been excluded.
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PMID:Metabolic regulation of renal gluconeogenesis in response to sepsis in the rat. 217 16


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