UMLS:C0036690 - FACTA Search

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

The body clearance of 10 plasma amino acids (AA) was determined from the rate of compared muscle-released AA and AA administered by infusion of total parenteral nutrition (TPN) compared to their estimated extracellular (ECW) pool in patients with multiple trauma with (n = 10) or without (n = 16) sepsis at 8-hour intervals. In both nonseptic and septic trauma, increasing TPN increased the mean clearance rate of all infused AA. When the individual AA clearance rates were normalized by the total AA infusion rate, regression-covariance analysis revealed that patients with sepsis had relatively impaired clearances of alanine (p less than 0.01) and methionine, proline, phenylalanine, and tyrosine p less than 0.05 for all). In contrast, the clearances of branched-chain AA (BCAA) valine and isoleucine were maintained, and the clearance of leucine was higher (p less than 0.05) in trauma patients with sepsis than in those without. At any AA infusion rate, compared with surviving patients with sepsis (p less than 0.05), patients who developed fatal multiple organ failure syndrome (MOFS) showed increased clearances of all BCAA with further impaired clearance of tyrosine. The clearance ratio of leucine/tyrosine was increased in MOFS at any AA infusion rate (p less than 0.0001), was an indicator of severity, and, if persistent, was a manifestation of a fatal outcome. Because tyrosine metabolism occurs almost entirely in the liver while leucine can be utilized by viscera and muscle, these data suggest early and progressive septic impairment of the pattern of hepatic uptake and oxidation of AA with a greater body dependence on BCAA, especially leucine, as septic MOFS develops.
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PMID:Increased dependence of leucine in posttraumatic sepsis: leucine/tyrosine clearance ratio as an indicator of hepatic impairment in septic multiple organ failure syndrome. 403 61

A male infant had severe muscular hypotonia from birth. Recurrent vomiting with dehydration and severe metabolic acidosis complicated the course. Elevated lactate (up to 12.3 mmol/l; n less than 2), pyruvate (0.4 mmol/l; n less than 0.05) and alanine levels were found in serum with an abnormal lactate/pyruvate ratio (greater than 30; n less than 15). In urine the concentrations of lactate, pyruvate, alanine and of several intermediates of the citric acid cycle were increased. In muscle, numerous disseminated "ragged red fibres" were found by light microscopy; muscle fibres were found to contain subsarcolemmal aggregates of mitochondria, lipid droplets and glycogen by electromicroscopical methods. Moreover, mitochondria with a typical circular arrangement of cristae were noticed. In liver homogenates normal activities of pyruvate carboxylase and pyruvate dehydrogenase complex were found; in liver mitochondria also succinate-cytochrome-c-oxidoreductase activity was normal. However, in muscle no succinate-cytochrome-c-oxidoreductase activity was detectable. The patient became increasingly lethargic and died because of sepsis at 5 months of age.
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PMID:Mitochondrial myopathy with lactic acidosis and deficient activity of muscle succinate cytochrome-c-oxidoreductase. 609 51

The phosphonopeptide L- norvalyl -L-1- aminoethylphosphonic acid [ Nva -Ala(P)] has been studied in combination with 12 beta-lactam antibiotics for activity against Pseudomonas aeruginosa. Nocardicin A was found to give the most potent synergistic combination with Nva -Ala(P). This interaction was widely observed in clinical isolates of P. aeruginosa in vitro and in a mouse septicemia model. Synergy was also observed in vitro and in vivo in several other species, including Proteus mirabilis, indole-positive Proteus spp., and Serratia marcescens. The interaction between Nva -Ala(P) and nocardicin A involved a strongly bacteriolytic mechanism. In addition, the individual components were complementary to one another in their action against organisms not showing synergy. These properties resulted in a broad spectrum of activity of the combination Nva -Ala(P) plus nocardicin A when used to treat experimental gram-negative bacterial infections.
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PMID:Synergistic antibacterial activity between L-norvalyl-L-1-aminoethylphosphonic acid and nocardicin A. 642 12

The concentrations of acetoacetate, beta-hydroxybutyrate, and adenine nucleotides, and the mitochondrial phosphorylative activities, induced by cecal ligation and punctured in the liver of septic rats, were determined. The concentrations of glucose, free fatty acids (FFA), and free amino acids in arterial blood were also studied along with ketone body concentrations. Hepatic energy charge levels decreased from 0.84 to 0.77 at 12h after the induction of sepsis (P less than 0.01) and to 0.60 at 18h (P less than 0.001). Mitochondrial phosphorylative activity was enhanced at 6h (P less than 0.001) and decreased at 18h later. Ketone body concentrations in the liver and the arterial blood decreased concomitant with the decrease in hepatic energy charge. The mitochondrial redox state increased significantly at 12 and 18h after the induction of sepsis (P less than 0.01) concomitant with a marked decrease in the concentrations of ketone bodies (P less than 0.01). Blood glucose levels remained within normal limits except for a transient increase at 6h, but plasma FFA levels decreased (P less than 0.01). The plasma concentrations of aromatic amino acids (P less than 0.001), proline, and alanine (P less than 0.05) increased slightly at 18h. It is suggested that the ketogenic capacity of the liver is inhibited during sepsis, but that the liver maintains gluconeogenesis at relatively normal levels until a more advanced stage of sepsis.
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PMID:Ketogenesis during sepsis in relation to hepatic energy metabolism. 649 93

To investigate the effects of bacterial infection on glucose and alanine metabolism, a variety of studies were carried out in rat and monkey models. These included glucose turnover by a pulse-dose technique in infected rats; alanine and glucose production and utilization in control and septic monkeys; in vivo measurement of gluconeogenesis in rats, with and without an alanine load; the in vitro rate of glucose formation from various substrates by isolated liver perfusion and hepatic cells; and in vivo rates of oxidation of glucose labeled with 14C at the 1 or 6 carbon position. In rats, glucose turnover was markedly accelerated 24 hr after inoculation of either 10(4) or 10(7) Streptococcus pneumoniae. Glucose utilization and production were also accelerated during illness and early recovery from a pneumococcal infection in monkeys. The rates of gluconeogenesis as measured by either a pulse technique in rats or continuous infusion of labeled alanine in monkey were significantly elevated during pneumococcal septicemia. During the agonal stages (10(7) of the pneumococcal infection in rat, an alanine load resulted in a decreased rate of labeled glucose production and an increase in plasma glucose when compared to values of fasted control rats. However, early illness caused similar or increased rates of glucose production from alanine in vivo. Similar reduced rates of glucose formation were observed when the isolated livers or hepatocytes from rats during the agonal stages of infection were perfused with excess quantities of gluconeogenic substrates. Thus, in the rat, gluconeogenic capacity (ability to form glucose from excess substrates) appears to decrease only during the agonal stages of pneumococcal infection. During acute pneumococcal sepsis in the rhesus monkey, alanine production and utilization were significantly elevated and it was estimated that over 90% of the newly produced alanine was utilized for glucose synthesis. When arterial--venous differences were measured across the hindquarters, significantly more alanine was released, presumably from skeletal muscle of the septic monkey, compared to the recovery period or in the control groups. Thus, the increase in glucose synthesis in both rat and monkey appears to be correlated with substrate availability and kinetic rate, rather than gluconeogenic capacity of the liver. The major increase in glucose utilization during both S. pneumoniae and Francisella tularensis live vaccine strain (LVS) infections in rat was a progressive elevation in the rate of oxidation via the pentose phosphate shunt in the rat. Further, the rate of oxidation appeared to be correlated with the magnitude of the bacteremia, which is an indication of the severity of the infection...
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PMID:Glucose and alanine metabolism during bacterial infections in rats and rhesus monkeys. 676 54

Forty-six patients with surgical sepsis were studied prospectively until death or survival to evaluate the effect of exogenous metabolic support on the observed plasma substrate levels and on the differential endogenous utilization of branch chain amino acids. There were no effects of administered glucose or colloid load. The administered amino acid load had little effect on substrate levels in patients who died; but significantly effected the observed levels of glycine, isoleucine, and methionine in patients who survived. Evidence is presented which suggests that fatal sepsis is associated with an increased release of endogenous valine and isoleucine into plasma, as well as increased plasma levels of tyrosine, proline, and methionine. These abnormalities are highly correlated with the increased levels of plasma alanine and occur at a time when the nonsurviving septic patient manifests a tendency toward reduced oxygen consumption and abnormal vascular tone relations--the septic B state. These data are consistent with the hypothesis that increased muscle protein catabolism is occurring with a differential utilization of branch chain amino acids and increased use of leucine and isoleucine and reduced use of valine. This autocannibalism of muscle mass appears to be the source of the increased plasma alanine and is little influenced by administered amino acid support in the absence of control of the septic process.
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PMID:Septic autocannibalism. A failure of exogenous nutritional support. 677 5

A prospective and randomized study was performed in 18 patients with septic peritonitis to investigate the behavior of free amino acids in serum before and during parenteral nutrition with 2 different amino acid solutions. One group received a so called "liver-solution" with 45% branched chain amino acids and reduced aromatic and sulphur-containing amino acids, the other group a conventional solution with 10,5% branched chain amino acids. Amino acid imbalances typically in sepsis--elevation of aromatic and sulphur-containing amino acids as well as alanine and proline, normal or decreased branched chain amino acids--could be observed only to some extend, because the influence of preceding operative trauma was overlapping. However, with conventional parenteral nutrition these imbalances then became clearly apparent. On the other hand, in patients treated with the special amino acid solution nearly complete normalization of amino acid levels took place. This effect was mainly due to the increased supplementation of branched chain amino acids positively influencing protein metabolism, and less produced by the changes in amino acid proportions supplied. Clinically these patients also had a clear improvement of consciousness status. The positive effect of such balanced solution on amino acid metabolism and mental situation of septic patients could be confirmed. Their use in septic peritonitis during necessary parenteral nutrition as an adjunctive treatment therefore seems to be efficient.
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PMID:[Correction of amino acid imbalances as adjuvant therapy in septic peritonitis]. 684 Aug 31

Ketosis following starvation was suppressed by hindlimb infection in seven fasted sheep. Glucose production determined following the primed constant infusion of [6-3H(N)]glucose was elevated in the fasted-infected animals (9.50 +/- 1.11 mmol X kg-1 X min-1 (mean +/- SE) versus fasted controls (5.56 +/- 2.2). To determine if the ketonemia following sepsis contributed to the increased glucogenesis associated with catabolic disorder, glucose production and arterial substrates were measured before and after infusion of sodium-DL-beta-hydroxybutyrate (beta-OHB, 20 mumol X kg-1 X min-1) in fed, fasted, and fasted-infected animals. Following 3 h of beta-OHB infusion in the awake conditioned animals, beta-OHB and acetoacetate blood concentrations more than doubled. With infusion, blood glucose and alanine concentrations decreased in the fed and fasted sheep but not in the fasted-infected group. Glucose production fell significantly from 10.11 +/- 1.33 to 8.44 +/- 1.05 in the fed animals and from 5.05 +/- 0.28 to 4.11 +/- 0.33 in the fasted group. Glucose production was unaffected by beta-OHB infusion in the fasted-infected animals (9.50 +/- 1.83 vs. 9.11 +/- 1.44). The accelerated rate of glucose production in sheep following infection is not a consequence of the hypoketonemic state associated with sepsis.
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PMID:Ketone-glucose interaction in fed, fasted, and fasted-infected sheep. 684 75

Nitrogen flux across the splanchnic bed is altered following operation, injury, and sepsis, but the individual contributions of gut and liver and their interrelationships remain undefined. Since more than 60% of whole blood amino acid nitrogen is transported as glutamine and alanine, we determined the flux of these amino acids across the gastrointestinal tract and liver in splenectomized, awake dogs during a control period and a 2 and 4 days following a standard laparotomy. Blood flow was measured in all studies and substrate flux calculated from flow and arteriovenous and portovenous concentration differences. Portal blood flow decreased by 25% following operation from a control value of 26 +/- 2 ml/kg body weight . min to 19 +/- 2 (P less than 0.05). Total hepatic blood flow did not change significantly after operation, but the individual contributions of the hepatic artery and portal vein were altered; hepatic artery flow increased from a control value of 10 +/- 1 ml/kg . min to 23 +/- 3 (P less than 0.001). Glutamine uptake by teh gastrointestinal tract nearly doubled from a control value of 0.75 +/- 0.16 microM/kg . min to 1.31 +/- 0.13 (P less than 0.05) on postoperative day 2. This increase in flux occurred despite a diminished arterial concentration and a reduced portal blood flow, indicating that extraction of glutamine by the gastrointestinal tract was not primarily dependent on increased arterial concentration. Alanine, on the other hand, was released by the gut at a rate of 1.97 +/- 0.37 microM/kg . min in controls and decreased to 0.81 +/- 0.13 microM/kg . min (P less than 0.05) in dogs that had operation. Glutamine was released by the liver in control dogs at a rate of 1.59 +/- 0.59 microM/kg . min but switched to an organ of slight glutamine uptake (0.31 +/- 0.31, P less than 0.01) on postoperative day 2. Alanine uptake by the liver doubled from 2.94 +/- 0.29 to 5.46 +/- 0.63 microM/kg . min (P less than 0.05) following surgical stress. The gastrointestinal tract plays an active metabolic role in the processing of amino acids following operation and may be a key regulatory of interorgan substrate flux following injury and infection.
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PMID:Postoperative alteration of arteriovenous exchange of amino acids across the gastrointestinal tract. 687 48

This paper describes the development of a sustained sepsis model, using chronically catheterized conscious unrestrained rats, which simulates the progression of septicemia in man, including a sustained hypermetabolic phase. Following chronic arterial catheterization, sepsis was induced in rats by intraperitoneal administration of 0.5 ml of a pooled fecal inoculum. The pooled inoculum, which was used to ensure a uniform inoculation of microorganisms to all animals, produced a septicemia which was progressively lethal. The resultant peritonitis was characterized as polymicrobial, with gram-negative bacteria being continuously present in both peritoneal fluid and blood. Septic animals were normotensive but tachycardic, compared to time-matched controls, throughout the observation period. In contrast to the stable colonic temperature of control animals, septic rats showed a significant febrile response on the first 3 days following inoculation. The hypermetabolic response in septic rats was also manifested by a 25, 38, and 28% increase in oxygen consumption on Days 1, 2, and 3 postinoculation. Animals responded to sepsis with a fall in blood glucose (on Day 2) which remained 15--20% below control levels. Mild hyperlactacidemia (2 mM) and reduced alanine concentrations (14--33%) were also seen in the septic group on Days 2 through 5. Despite the increased lactate levels, septic animals were mildly alkalotic (pH 7.51) which probably reflected the increased (32%) respiratory rate. Light microscopic findings in the septic animals revealed a spectrum of morphologic lesions including an extensive fibrinopurulent exudate, bacterial colonies, and abscesses, which involved most of the abdominal viscera. This investigation characterizes an experimental model of sustained sepsis in rats which exhibits hemodynamics, metabolic and pathologic alterations similar to those seen in human peritonitis.
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PMID:Sustained hypermetabolic sepsis in rats: characterization of the model. 688 40

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