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

Since plasma alanine concentrations are markedly elevated in late sepsis and alanine is an important gluconeogenic substrate, we investigated gluconeogenic activity in intra-abdominal sepsis. Sepsis in rats was produced by cecal ligation and puncture. After 17 to 21 hours (late sepsis, LS) livers from these and sham-operated rats were isolated and perfused at constant flow with Krebs buffer in the presence or absence of 10 mM alanine. Various phenylephrine (PE) concentrations were also used to measure gluconeogenic response to alpha-adrenergic stimulation. The results showed that glucose production from alanine by livers from LS rats was depressed in comparison to livers from sham rats (2.6 +/- 0.2 vs. 4.2 +/- 0.4 moles/gm/hr). Moreover, although livers from rats in LS responded to PE stimulation in a dose-dependent manner, the magnitude as well as the threshold of response was decreased in comparison to shams. In contrast to glucose production, VO2 of the sham and LS were not different under any conditions. Previous studies using lactate as a substrate, however, showed that both gluconeogenesis and oxidative responses were decreased in LS. Since hepatic gluconeogenic but not VO2 response was depressed with alanine, these results indicate that the decreased gluconeogenic capability precedes depressed oxidative capability in sepsis.
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PMID:Hepatic gluconeogenic capability in sepsis is depressed before changes in oxidative capability. 712 May 23

Abdominal surgery increases blood glucose concentration and peripheral release and splanchnic uptake of gluconeogenic substrates, including alanine. During trauma or sepsis, infusion of glucose fails to depress alanine conversion to glucose. The effect of intra-operative glucose infusion on splanchnic metabolism was examined in the present study. In eight patients undergoing elective cholecystectomy, splanchnic glucose metabolism was investigated before, during and immediately after surgery. Glucose was infused at a constant rate of 1 mmol/min. Splanchnic blood flow and arterio-hepatic venous differences of oxygen, glucose, lactate, glycerol, 3-hydroxybutyrate and alanine were measured. Eight other patients, who received saline instead of glucose, served as a control group. Infusion of glucose resulted in total inhibition of splanchnic glucose release before as well as during and immediately after surgery. This was observed, even before surgery, at an arterial glucose level which was lower than that in the control group at the end of and immediately after surgery, at which no decrease of the splanchnic glucose release was recorded. changes in neuronal and hormonal factors due to the surgical trauma are considered responsible for this difference in glucose homeostasis. Splanchnic alanine uptake increased during surgery in both groups, but tended to be somewhat lower in the glucose group. The arterial glycerol concentration and splanchnic uptake, as well as the arterial concentration and splanchnic release of 3-hydroxybutyrate, were reduced. It is concluded that an intravenous infusion of glucose at the rate of 1 mmol/min during abdominal surgery (a) increases the arterial blood glucose level and abolishes splanchnic glucose release, (b) reduces, but does not totally prevent the increase in splanchnic uptake of gluconeogenic substrates, and (c) diminishes lipolysis and the formation of 3-hydroxybutyrate.
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PMID:Influence of abdominal surgical trauma and intra-operative infusion of glucose on splanchnic glucose metabolism in man. 719 97

The blood concentrations and the disappearance of injected beta-hydroxybutyrate (beta-OHB) and alanine were measured in 12 health subjects who had fasted overnight and in 25 surgical patients. Ten of the patients had had uncomplicated abdominal surgery two of five days before, six patients had moderate sepsis e.g. wound sepsis and nine patients had severe intra-abdominal sepsis. Separated bolus injections of beta-OHB and alanine were given intravenously and the blood concentration of the corresponding metabolite was measured over the following 40 mins. The disappearance of the injected metabolite was logarithmic, and the half-life (t 1/2) and clearance rate of the injected metabolite were calculated. The basal ketone concentration (beta-hydroxybutyrate and acetoacetate) were higher in the post operative group than in healthy subjects whereas the severely septic group had the same ketone concentration as the healthy subjects. Alanine concentration was significantly lower in the post-operative group. The t 1/2 and clearance rate of the injected metabolites were similar in all the groups for both beta-hydroxybutyrate and alanine. It is suggested that if the bolus is handled like the endogenously produced metabolite then the differences in concentration of beta-OHB and alanine in post-surgical and septic patients are likely to be due to changes in production rate.
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PMID:Blood concentration and disappearance of injected alanine and beta-hydroxybutyrate in surgical patients. 727 92

Excessive coagulation is a typical response to the vascular injury occurring in gram negative sepsis. This study evaluated the pharmacological effects of the use of a recombinant Escherichia coli derived form of tissue factor pathway inhibitor (ala-TFPI) in a baboon model of septic shock. Several doses of ala-TFPI were administered either 30 or 120 min after the initiation of a lethal intravenous infusion of E. coli into baboons. Treatment at 30 min with either 2.7 or 7.4 mg/kg of ala-TFPI resulted in the same survival rates and attenuation of both the coagulation response and cellular injury, as measured by clinical chemistry. When administration of ala-TFPI was delayed for 120 min, a dose of ala-TFPI protein continued to provide a benefit to survival. Ala-TFPI reduced the drop in mean systemic arterial pressure compared to control baboons in addition to partially attenuating the coagulopathic response. Baboons given ala-TFPI also maintained lower levels of plasma interleukin-6 (IL-6) and thrombin-antithrombin. These results suggest that the site of action of the protein may involve the later stage components of the coagulation and inflammatory pathways.
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PMID:Recombinant E. coli-derived tissue factor pathway inhibitor reduces coagulopathic and lethal effects in the baboon gram-negative model of septic shock. 760 Jun 36

Long-term results of 13 liver transplantations in patients with a previous diagnosis of type I familial amyloid polyneuropathy (FAP) are presented. The diagnosis of type I FAP was based on the presence of a biochemical marker in the plasma (TTR-Met-30 in 11 patients, TTR-Ala-71 in two). Maximum follow-up is 28 months and the survival rate stands at 11 of 13 patients. Two patients died from sepsis at 2 and 6 months. TTR disappeared from plasma in all cases. Neurological status improved in all eight patients undergoing transplantation more than 6 months previously, although electromyographic studies showed a slight improvement only in the six with follow-up of more than 1 year. All 13 patients showed a hyperdynamic haemodynamic pattern with a high incidence (four patients) of the use of venovenous bypass due to haemodynamic intolerance. Two patients also received transplants by the 'piggy-back' technique. In conclusion, liver transplantation may be useful in the treatment of certain patients with FAP to halt and improve the neurological consequences of the disease.
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PMID:Clinical improvement after liver transplantation for type I familial amyloid polyneuropathy. 762 23

An increase in gluconeogenesis contributes to the cachexia seen in severe injury, sepsis, and malignancy by converting amino acids from skeletal muscle to glucose. Since tumor necrosis factor alpha (TNF alpha) may mediate this cachexia, we examined the effect of this cytokine on gluconeogenesis. Twenty-eight male Fischer rats were injected intraperitoneally with TNF alpha (250 micrograms/kg) or saline, and after 4 hours, isolated hepatocytes were obtained by in situ collagenase liver perfusion. Hepatocytes were incubated with alanine (10 mM), and rates of gluconeogenesis were determined. Plasma lactate, glucose, insulin, glucagon, cortisol, and amino acids were measured. TNF alpha administration resulted in a 50% increase in gluconeogenesis from alanine (P < 0.05) and a three-fold increase in plasma glucagon (P = 0.01). Total and glucogenic plasma amino acids decreased with TNF alpha injection (P < 0.05). In vivo TNF alpha causes an increase in hepatic gluconeogenesis associated with increased plasma glucagon.
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PMID:Tumor necrosis factor alpha stimulates gluconeogenesis from alanine in vivo. 763 Jan 67

The effects of endotoxin on the activities of the major Na(+)-independent amino acid transporters in rat liver (Systems n, asc, L, bo,+, and y+) were studied using using hepatic plasma membrane vesicles (HPMVs). Rats were treated with a single dose of Escherichia coli endotoxin (E. coli lipopolysaccharide 0127:B8 (LPS), 7.5, 15, or 30 mg/kg BW) and HPMVs were prepared by Percoll density gradient centrifugation at various timepoints after LPS administration. Vesicle purity and integrity was established by assay of enzyme markers and identical equilibrium uptakes. The activities of the Na(+)-independent amino acid transport systems y+ and bo,+ (arginine), asc (alanine and cysteine), L (leucine), and n (glutamine) were evaluated by measuring the uptake of radiolabeled amino acids using a rapid mixing/filtration technique. Amino acid uptake by HPMVs consisted of saturable and nonsaturable components. Prior treatment with endotoxin did not alter the activities of Systems n, asc, or L but resulted in a time- and dose-dependent stimulation of saturable arginine transport. Arginine transport increased within 2 h of LPS administration and exhibited a return towards basal levels by 24 h. Nonsaturable uptake (diffusion) in HPMVs was unaltered by LPS treatment. Kinetic analysis of arginine transport demonstrated the presence of both a high affinity and a low affinity carrier. Treatment with LPS resulted in a 73% increase in the Vmax of the high affinity carrier (System y+) and a 25% increase in the Vmax of the low affinity transporter (System bo,+). The data indicate selective stimulation of Na(+)-independent arginine transport in the liver during endotoxemia which may serve to support important arginine-dependent pathways during sepsis.
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PMID:Hepatic Na(+)-independent amino acid transport in endotoxemic rats: evidence for selective stimulation of arginine transport. 774 45

The effects of administering total parenteral nutrition (TPN) supplemented with the dipeptide of L-alanyl-L-glutamine (Ala-Gln) on gut structure, barrier function, and protein metabolism were investigated in septic rats. Sepsis was induced by the continuous intraperitoneal administration of endotoxin via a miniosmotic pump. Twenty-three rats were divided into two groups and fed parenterally for 5 days. The Ala-Gln group (n = 11) received a conventional TPN solution supplemented with 2% Ala-Gln, whereas the control group (n = 12) received conventional TPN solution alone. One rat in each group died of endotoxemia. The groups showed similar nitrogen balance, urinary excretion of 3-methylhistidine, and plasma concentration of endotoxin in the portal vein. The groups showed similar incidence of bacterial translocation from the gut to the mesenteric lymph nodes. The intestinal mucosal weight and villous height were significantly greater in the Ala-Gln group than in the control group. Pathological derangement of the mucosal structure was more marked in the control group than in the Ala-Gln group. These results suggest that TPN supplemented with Ala-Gln preserves the gut structure without decreasing the nitrogen balance under septic conditions.
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PMID:Total parenteral nutrition supplemented with L-alanyl-L-glutamine and gut structure and protein metabolism in septic rats. 791 76

Group B streptococci (GBS) are important pathogens in neonatal sepsis, pneumonia, and meningitis. The ability of GBS to invade the collagen-rich amniotic membrane of the placenta has been shown in vitro. In the presence of GBS, the collagen fibrils of the amnion appear disordered, suggesting a role for GBS in premature rupture of membranes. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis, Sephadex G-200 column chromatography, and gelatin zymograms were used in this study to characterize cell-associated collagenolytic activities of GBS. The synthetic peptide 2-furanacryloyl-Leu-Gly-Pro-Ala (FALGPA), which mimics the primary structure of collagen, was degraded by GBS USF704, a clinical isolate from the placenta of a septic newborn. Cells of GBS USF704 (9 x 10(7) CFU/ml) hydrolyzed 902 nmol of FALGPA over a 24-h period. As reported for zinc metalloenzymes such as collagenase, the hydrolysis of FALGPA by GBS was inhibited by addition of EDTA or 1,10-phenanthroline. Boiling of the cells resulted in loss of activity, while higher activity was observed with crude GBS cell lysates (hydrolysis of 970 nmol of FALGPA in 1.5 h). Antiserum raised against collagenase from Clostridium histolyticum was found to cross-react with cell-associated proteins produced by GBS and to inhibit GBS FALGPA hydrolysis. Twenty-five additional GBS clinical isolates were screened and found to have various levels of FALGPA hydrolytic activity. These observations suggest a cell-associated collagenolytic activity by GBS which may be involved in premature rupture of membranes and neonatal disease.
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PMID:Cell-associated collagenolytic activity by group B streptococci. 796 Jan 47

Concentrations of amino acids in plasma and whole blood in response to 10 hours of food deprivation were determined in healthy 2-day-old foals (n = 8) and were compared with control values in foals of the same age (n = 8) allowed free access to suckle. In addition, response of concentrations of amino acids in plasma to 15 minutes of free-access suckling was determined at the end of the 10-hour period in both groups. Response of 13 amino acids in plasma of food-deprived foals was significantly (P < 0.05) different, compared with that in control foals. Concentrations of 3 amino acids (alanine, glycine, and phenylalanine) in plasma increased significantly (P < 0.05), whereas concentrations of 7 amino acids (asparagine, citrulline, histidine, ornithine, proline, tryptophan, and tyrosine) in plasma decreased significantly (P < 0.05) during food deprivation. Response of concentrations of 2 amino acids (glycine and histidine) in whole blood was significantly (P < 0.05) different from that in plasma of food-deprived vs control foals. Refeeding of food-deprived foals resulted in significantly (P < 0.05) different responses for concentrations of all but 2 amino acids (cystine and taurine) in plasma, compared with responses in controls. Changes in concentrations of amino acids in plasma and whole blood of foals in response to food deprivation are similar to those in foals with septicemia and in children with grade 1 or 2 kwashiorkor. The significantly different response of food-deprived foals to refeeding may be attributable to increased protein intake or altered physiologic state.
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PMID:Concentrations of amino acids in plasma and whole blood in response to food deprivation and refeeding in healthy two-day-old foals. 797 19


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