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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sepsis has been associated with specific plasma amino acid patterns. Sixty-five patients were prospectively investigated as to whether these patterns are indeed sepsis specific, or specific for metabolic stress without concomitant sepsis, or associated with the presence of organ failure. Virtually all aminoacid levels were decreased by 10-30% (p less than 0.05), whereas cystine and phenylalanine were significantly elevated. These changes were more pronounced in severe sepsis. Organ failure was not associated with significantly altered amino acid profiles. No differences were found between sepsis and stress without signs of sepsis. In addition, imminent death was not associated with aberrant amino acid profiles. We conclude that sepsis and metabolic stress are associated with changes in plasma amino acid profiles, but that such changes are aspecific and therefore poor indicators of disease severity.
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PMID:Plasma-amino acid profiles in sepsis and stress. 291 Feb 15

Cecal ligation and puncture (CLP) has been extensively used as a model of sepsis in adult rats. It is not known if the response to sepsis is similar in young and adult rats. This investigation was done to compare hemodynamic and metabolic alterations in young (four to six weeks of age, 60 to 90 grams) and adult (12 to 14 weeks of age, 270 to 340 grams) rats after CLP. In one series of experiments, survival rate was determined for 96 hours, and in other experiments, mean arterial blood pressure (MAP), heart rate (HR), white blood cell count, hematocrit, platelets, plasma glucose, lactate, amino acids, blood urea nitrogen (BUN), blood and peritoneal cultures and resting energy expenditure (REE) were determined eight and 16 hours after CLP. Levels of glycogen in liver and muscle were determined 16 hours after CLP. Mortality rate was similar in young and adult rats. MAP was stable throughout the course of sepsis, with no significant differences between the two groups of rats. HR was higher in young rats at all times studied. The adult rats became hyperglycemic after CLP while the young were hypoglycemic eight hours after CLP but normalized at 16 hours. Plasma lactate and BUN were similar in the two groups of rats, and no alterations were seen during sepsis. Both young and adult rats became hypoaminoacidemic after CLP. The phenylalanine to tyrosine ratio increased in a similar manner during sepsis in both experimental groups. REE was higher in young than in adult rats, but no significant changes were observed during the course of sepsis in either group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hemodynamic and metabolic alterations during experimental sepsis in young and adult rats. 291 92

Neutrophil superoxide production has been recognized as an important pathway for microbicidal activity and regulation of the local inflammatory environment. To investigate neutrophil superoxide production in sepsis, we studied 22 patients with intra-abdominal infections, and correlated superoxide production with chemotactic response and granular enzyme content. Our results showed that neutrophils from infected patients had specific loss of chemotactic response to C5a, and were deficient in the granular enzymes, lysozyme, and beta-glucuronidase. Superoxide production in response to opsonized zymosan was intact, but response to the chemoattractant N-formyl-methionyl-leucyl-phenylalanine was markedly depressed. This could be reversed in vitro by the addition of cytochalasin B. These results suggest that down regulation of exocytosis of superoxide to nonphagocytic stimuli occurs during sepsis, possibly protecting the host from tissue injury due to oxide radical release. Superoxide response to phagocytic stimulation was intact.
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PMID:Regulation of neutrophil superoxide production in sepsis. 298 24

Using the superoxide dismutase inhibitable reduction of cytochrome c assay, we studied, the effect of (-) naloxone on N-formyl-methionyl-leucyl-phenylalanine (FMLP) stimulated superoxide (O2-) release from human neutrophils. Neutrophils were pre-incubated with the range of concentrations of (-) naloxone that is administered in models of experimental sepsis (10(-6) - 10(-4.5) M). (-) Naloxone inhibited O2- release in a dose dependent manner. 02- produced by a cell-free xanthine-xanthine oxidase system was not inhibited by (-) naloxone, indicating that (-) naloxone was not scavanging O2-. There was no difference between the effect of (-) and (+) naloxone suggesting that the inhibition of O2- was not specific for an opiate receptor. Another opiate antagonist, nalorphine, as well as the opiate agonist, morphine, also inhibited O2- release in the same concentration range. There was no difference between the effect of naloxone and morphine.
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PMID:Naloxone inhibits superoxide release from human neutrophils. 299 44

The hypothesis has been advanced that the human systemic septic response is a function of the host and not of the type of infecting organism. Metabolic and physiologic data from five immunosuppressed transplant recipients with isolated cytomegaloviral sepsis and viremia were prospectively evaluated. Serial cultures obtained from lung, sputum, urine, wound, blood, and invasive lines were positive for virus and negative for bacterial or fungal pathogens. The results were compared with two data banks derived from either victims of multiple trauma without sepsis or surgical patients with early bacterial or fungal sepsis. Statistically significant differences between the patients and the nonseptic reference group were noted for cardiac index, total peripheral resistance, arteriovenous oxygen content difference, oxygen consumption, and levels of triglycerides, proline, phenylalanine, tyrosine, alpha-aminobutyrate, and alanine. No such differences were present for these data compared with the septic reference group. Physiologic data obtained just before death in three patients indicated a failure of oxygen transport. It appears that the systemic septic response to viral agents is indistinguishable by physiologic and metabolic criteria from that resulting from bacterial or fungal agents.
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PMID:Physiology and metabolism in isolated viral septicemia. Further evidence of an organism-independent, host-dependent response. 302 82

A method, devised in the authors' laboratories, for the determination of C3b receptors on normal and patient neutrophils using C3b-coated fluorescent microspheres, was applied to the quantitation of C3b receptors on the neutrophils of several patients suffering from burns and trauma and a patient with pancreatitis. From three to 11 days in the clinical course the relative number of C3b receptors was, or rose to, two to ten times the number of receptors present at later times in the clinical course and, in most of the cases studied, the increase in C3b receptor number coincided with enhanced neutrophil bactericidal function. The rise in C3b receptor number was ascribed to up-regulation by C3a and C5a des Arg from complement activation and also, in the cases where sepsis occurred, to the presence of bacterial chemotactic peptides. Preliminary experiments with zymosan-activated serum and the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine confirmed this explanation.
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PMID:Determination of C3b receptors on normal and patient polymorphonuclear neutrophils with C3b-coated fluorescent microspheres. 315 8

Using fluorogenic substrates and the specific inhibitor E-64, cysteine proteinase (CP) activity was measured in blood plasma of healthy controls (mean = 35.0 mU/l) and patients with cancer and severe septic shock. Whereas moderately elevated activity was observed in some kinds of cancer (mean = 63.9 mU/l), 10-fold increased CP activity was found in septic shock. The plasma CP activity of sepsis patients paralleled the immunologically determined concentration of elastase-alpha 1-proteinase inhibitor complex. On the basis of its substrate specificity and its Michaelis constant for Z-Phe-Arg-NMec the plasma CP was identified as cathepsin B or a cathepsin B-like proteinase (CBP). Kinetic studies revealed that dilution and competition with substrate effects reversible dissociation of CBP from complexes with plasma inhibitors that are most probably the kininogens. The dissociation of CBP was confirmed by gel chromatographic fractionation of the plasma proteins. The results suggest that active CBP can easily dissociate from its plasma inhibitor complexes in vivo and may be involved in pathogenetic extracellular proteolysis.
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PMID:Enzymatically active cathepsin B dissociating from its inhibitor complexes is elevated in blood plasma of patients with septic shock and some malignant tumors. 320 66

Sepsis was induced by cecal ligation and puncture in male Sprague-Dawley rats weighing approximately 70 g and the animals were intravenously infused with one of four isocaloric solutions: group I (N = 16), 8.5% dextrose solution; group II (N = 16), alpha-ketoisocaproic acid (KIA, 5.1 mg/ml) in 8.5% dextrose; group III (N = 16), FreAmine HBC (containing 45% branched-chain amino acids) in 2.5% dextrose; and group IV (N = 17), FreAmine HBC in 2.5% dextrose + KIA (5.1 mg/ml). Eighteen hr after induction of sepsis, extensor digitorum longus (EDL) and soleus (SOL) muscles were dissected with intact tendons and incubated for the study of protein synthesis and degradation, which were measured as incorporation of 14C-phenylalanine into protein and release of tyrosine into incubation medium, respectively. Urine was collected for determination of nitrogen balance. Nitrogen balance, which was equally negative in groups I and II, was significantly improved in groups III and IV and became equally positive in these groups. Protein synthesis and degradation rates in incubated EDL and SOL muscles were similar to those which we have reported previously in septic rats. Except for a higher synthetic rate in SOL in group II, no other differences in protein synthesis or degradation rates between the four experimental groups were found. Thus, the present study showed that infusion of a branched-chain amino acid-enriched solution improved nitrogen balance in septic rats. KIA alone or administered with the amino acid solution did not affect nitrogen balance.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Infusion of a branched-chain amino acid-enriched solution and alpha-ketoisocaproic acid in septic rats: effects on nitrogen balance and skeletal muscle protein turnover. 339 21

Chronic sepsis is always associated with profound wasting leading to increased release of amino acids from skeletal muscle. Net protein catabolism may be due to decreased rate of synthesis, increased rate of degradation, or both. To determine whether protein synthesis is altered in chronic sepsis, the rate of protein synthesis in vivo was estimated by measuring the incorporation of [3H]-phenylalanine in skeletal muscle protein in a chronic (5-day) septic rat model induced by creation of a stable intra-abdominal abscess using an E. coli + B. fragilis-infected sterile fecal-agar pellet as foreign body nidus. Septic rats failed to gain weight at rates similar to control animals, therefore control animals were weight matched to the septic animals. The skeletal muscle protein content in septic animals was significantly reduced relative to control animals (0.18 +/- 0.01 vs. 0.21 +/- 0.01 mg protein/gm wet wt; p less than 0.02). The rate of incorporation of [3H]-phenylalanine into skeletal muscle protein from control animals was 39 +/- 4 nmole/gm wet wt/hr or a fractional synthetic rate of 5.2 +/- 0.5%/day. In contrast to control animals, the fractional synthetic rate in septic animals (2.6 +/- 0.2%/day) was reduced by 50% compared to control animals (p less than 0.005). The decreased rate of protein synthesis in sepsis was not due to an energy deficit, as high-energy phosphates and ATP/ADP ratio were not altered. This decrease in protein synthesis occurred even though septic animals consumed as much food as control animals.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibition of skeletal muscle protein synthesis in septic intra-abdominal abscess. 339 97

Sepsis has been shown to decrease skeletal muscle glucose oxidation by inhibiting the pyruvate dehydrogenase activity (PDHa) and to increase proteolysis and use of branched-chain amino acids (BCAA). The effects of dichloroacetate (DCA), which reverses PDHa inhibition, were studied in skeletal muscle from a septic (S) rat model of intra-abdominal abscess (E. coli + B. fragilis) and compared to control (C) and sterile inflammatory abscess (I) animals. In one set of S, I, and C animals, DCA (1 mmol/kg) was injected intraperitoneally at 0, 30, and 60 min. Septic, but not I, rats had a twofold increase in skeletal muscle lactate concentrations over C, but no changes in pyruvate. After DCA, both lactate and pyruvate were reduced (p less than 0.001) to same level in S, I, and C. Skeletal muscle alanine was increased in S compared to I or C, but after DCA was reduced threefold in C, S, and I (p less than 0.001) suggesting that alanine synthesis may be impaired due to decreased pyruvate availability. Like alanine, skeletal muscle BCAA were increased in S compared to C, but not altered in I. Following DCA, BCAA levels in muscle from S were reduced (p less than 0.001) to values seen in C or I. Muscle phenylalanine content was significantly elevated in S (p less than 0.05) compared to C or I, but was reduced (p less than 0.05) after DCA in S but not in C or I. Decreased muscle phenylalanine associated with lowered BCAA suggests DCA may decrease septic muscle protein catabolism and/or enhance protein synthesis. Coupled with an increased PDHa and reduced lactate levels, this suggests that DCA may reverse the excess muscle catabolism and BCAA dependence of sepsis by increasing glucose and lactate oxidation and may be a useful therapeutic modality.
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PMID:Pharmacological reversal of abnormal glucose regulation, BCAA utilization, and muscle catabolism in sepsis by dichloroacetate. 341 55


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