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)

Protein turnover in cardiac and skeletal muscle is affected by the provision of amino acids, particularly the branched chain amino acids (BCAA). The effect of each of the BCAA, valine, leucine, and isoleucine, on the systolic function of isolated normal or septic rat heart perfused as a Langendorff preparation was examined. Thirty normal control and 28 septic rats (cecal ligation and puncture) were perfused with either Krebs + 8.5 mM glucose or Krebs + 5.0 mM glucose and 3.5 mM valine, leucine, or isoleucine. Septic hearts perfused with Krebs + 8.5 mM glucose exhibited developed force (DF) and force velocity (dF/dt) levels which were reduced to an average of 45 and 50%, respectively, compared to normal controls, and improved by 35% during 60 min perfusion over measurements made at time zero. In normal hearts DF and dF/dt decreased significantly during perfusion with leucine (27%) and isoleucine (20%). In sepsis, perfusion with leucine and isoleucine resulted in a mild improvement in systolic function. However, valine was far less effective than leucine and isoleucine in maintaining systolic function in sepsis, due apparently to valine being a less efficient energy substrate for the cardiac muscle in a state of severe energy deficit. Thus, valine, leucine, and isoleucine seem to exert different effects on the systolic function of normal and septic isolated rat hearts.
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PMID:The different effects of leucine, isoleucine, and valine on systolic properties of the normal and septic isolated rat heart. 398 17

The appearance of the adult respiratory distress syndrome (ARDS) during the course of acute illness is believed to result, in part, from intrapulmonary neutrophil sequestration and degranulation induced by circulating inflammatory mediators. To evaluate the role of complement-neutrophil interactions in the pathogenesis of ARDS in man, 34 patients suffering from intra-abdominal sepsis (seven), multisystem trauma (15), or acute pancreatitis (12) were serially studied with regard to neutrophil migratory responses to C5a and F-Met-Leu-Phe, lysosomal content of beta-glucuronidase and lysozyme, and simultaneously obtained plasma levels of immunoreactive C3adesArg and C5adesArg. Nineteen patients developed ARDS. In these patients, plasma C3adesArg levels obtained within 72 hours of admission to the hospital were elevated to 305 +/- 35 ng/ml compared with 145 +/- 16 ng/ml for patients who did not develop ARDS (p less than 0.0005). C5adesArg levels were not elevated in either group. In vitro studies showed that neutrophils from normal persons were able to clear all of the C5a/C5adesArg generated in up to 5% zymosan-activated serum, while no clearance of C3adesArg was identified. Patient migratory responses could be divided into three groups based on their initial (less than 72 hour) samples: (1) hyperresponsive to both N = formyl-methionyl-leucyl-phenylalanine (FMLP) and C5a, (2) specifically deactivated to C5a, and (3) deactivated to both C5a and FMLP. Patients in the latter two groups developed ARDS. Enzyme content of neutrophils from patients who developed ARDS showed a substantial fall in beta-glucuronidase and lysozyme levels. The finding of elevated plasma C3a levels and deactivation of migratory response to C5a support the contention that complement activation had occurred in these patients and that their neutrophils had been exposed to C5a/C5adesArg in vivo. The finding of nonspecific migratory dysfunction associated with lysozymal enzyme loss, a circumstance not reproducible in vitro by C5a exposure, suggests that other stimuli produced degranulation of neutrophils made hyperresponsive by prior exposure to C5a.
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PMID:Complement activation and clearance in acute illness and injury: evidence for C5a as a cell-directed mediator of the adult respiratory distress syndrome in man. 400 15

The oxidation of branched-chain amino acids following skeletal trauma or sepsis is considered a crucial event in the protein wastage that accompanies these stresses. This investigation undertook to monitor changes in leucine oxidation following bilateral femoral fracture to the rat to determine if this model is appropriate for monitoring specific amino acid oxidation after trauma. Thirty-five rats had hindlimb fractures and were fed an oral liquid diet ad libitum; 35 healthy rats were pair-fed with the trauma group. Food intake, body weight, and urinary nitrogens were monitored daily for all rats, and leucine oxidation was measured for five rats from each group on days 1 through 7 post-trauma. Leucine oxidation was qualitatively compared between the groups (from the percentage of isotope respired in 4 hours following a single injection of L-[l-14C] leucine). Skeletal fracture resulted in increased urinary nitrogen excretions on days 2 through 5 when compared to pair-fed animals. The traumatized rats compared to pair-fed controls had elevated leucine oxidation on days 2 through 4, and a tendency towards elevation on day 5. The peak in elevation occurred on day 3 when leucine oxidation was increased 49% above pair-fed rats. The data suggest an association between leucine oxidation and urinary excretion of nitrogen in this trauma model, and when the results are compared to our previous studies of leucine oxidation in traumatized patients, traumatized rats appear to respond similarly to injured patients in the acceleration of leucine oxidation.
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PMID:A rat model for evaluating leucine oxidation after skeletal trauma. 400 50

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

Markedly increased synthesis of alpha(2) and beta globulins and alpha(1), alpha(2), and beta glycoglobulins occurs during pneumococcal sepsis in the rat simultaneously with decreased albumin formation, diminished tritiated leucine incorporation into muscle protein, and enhanced excretion of nitrogen. This augmented synthesis of specific serum proteins does not become evident until fever and bacteremia develop, and it appears to be a fundamental aspect of host response to a proliferating bacterial infection in that it occurs even in rats fed a protein-deficient (6% protein) diet after weaning and before exposure to Diplococcus pneumoniae. Although amino acid catabolism, in general, appears to be increased during infection, tryptophan degradation via the kynurenine pathway, as assessed by measuring diazotizable urinary metabolites, changes little or is, at times, significantly less than in control animals. Coincidentally, functional tryptophan oxygenase activity decreases at 16 hr after exposure. Total tryptophan oxygenase activity, however, is unchanged.
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PMID:Nitrogen metabolism and protein synthesis during pneumococcal sepsis in rats. 440 82

The goal of nutritional support in sepsis is, as in other conditions, to prevent the use of endogenous protein as an energy substrate and, ideally, to promote the synthesis of proteins specifically required in responding to the particular insult or stress at hand. This entails provision of an utilizable fuel, in sufficient quantity, that does not inhibit the use of endogenous nonprotein sources; preservation of the existing protein mass by minimizing skeletal muscle and visceral proteolysis; provision of amino acids in sufficient quantity and in the appropriate proportions such that protein synthesis is optimized. Specifically, this includes the synthesis of those proteins required to maintain hyperdynamic function of the essential organs as well as the hepatic and leukocytic synthesis of proteins required in immunologic defense. This study has assessed one aspect of this goal during the administration of nutrient solutions differing primarily in branched chain amino acid content. We conclude that leucine is fundamental among the branched chain amino acids for reducing skeletal muscle proteolysis. Solutions designed for sepsis or stress should, therefore, contain adequate amounts of this amino acid.
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PMID:Infusion of branched chain-enriched amino acid solutions in sepsis. 642 47

Serum amino acid (AA) levels were determined for 18 cholecystectomy patients who had preserved and immediately utilized G-I function for absorption of 3,000 kcal/day elemental diet. Ten were given 132 gm AA/day; eight were given only 66 gm AA/day. Historical controls were 27 comparable patients who had received conventional hypocaloric intravenous (IV) regimens. Unfed patients' branched chain AAs (BCAAs) + TYR were depressed initially, then rebounded by day 3 or 4. Their glucogenic AAs were still depressed after 72 hours. Complete restoration of the basal pattern required five to ten days. Fully nourished patients maintained basal levels of all AAs on day 1. Every AA rose above basal, some with statistical significance as early as day 2. Moderately fed patients had BCAA depression, but for only 24 hours. LEU, ILE, VAL, TYR, MET, ASP, LYS, and ARG had already returned to basal levels on day 2, while the remaining AAs were much less depressed than in the unfed controls. All fed patients were discharged uneventfully 24-48 hours postcholecystectomy. The positive protein balance and elevated AA levels correlate with enhanced wound healing, host sepsis resistance, and shortened hospitalization.
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PMID:Elevation of postoperative plasma amino acid concentrations by immediate full enteral nutrition. 643 8

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

Liver blood flow and exchange of oxygen, glucose, lactate, and amino acids were measured in pigs at the same time as the peripheral arteriovenous (A-V) difference of these substances was determined. Four groups of animals were studied; they were normal postabsorptive, septic fasted, and septic infused either with complete parenteral nutrition (4.25% mixed amino acid solution with 25% glucose) or an isocaloric solution of 1.8% leucine with glucose. Sepsis in the pig caused a rise in arterial concentration of all essential amino acids except tryptophan and a decrease of most of the others. The liver uptake of the sum of all amino acids rose from nonsignificant values to 26.03 mumol/min/kg at the same time as the peripheral A-V difference changed from +20.4 to -678.0 mumol/l. Hyperalimentation increased arterial amino acid concentration, whereas peripheral A-V difference decreased to -132.3 mumol/l. The total liver uptake of amino acids was 24.80 mumol/min/kg but with a higher proportion of essential amino acids than in the fasted septic state suggesting increased liver protein synthesis. When leucine and glucose were infused the peripheral A-V difference of the sum of all amino acids was only -45.6 mumol/l indicating an almost complete cessation of muscle proteolysis. The arterial plasma concentration of all amino acids except leucine, glutamine, and glutamate were markedly reduced. Although hepatic clearance rate of amino acids fell only slightly, due to the low plasma concentrations, the liver uptake decreased substantially to 7.37 mumol/min/kg suggesting a decreased liver protein synthesis which could be deleterious in the presence of sepsis.
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PMID:The effects of hyperalimentation and infused leucine on the amino acid metabolism in sepsis: an experimental study in vivo. 678 84

Non-fasting plasma amino acids, proteins, anthropometric measurements, urea, and creatinine for 17 hemodialysis patients were compared with values in normal patients of similar age and sex. Values were characteristic for renal failure but with similarities to protein-energy malnutrition. Partial correlation coefficients, correcting for age and height, identified nutritional and non-nutritional factors. Plasma valine was the most correlated variable and was used to rank and group the patients. The group with valine less than 150 micrometers/liter had low values for 17 variables. Valine, isoleucine, leucine, threonine, asparagine, weight, and arm muscle circumference were interrelated and reflected malnutrition whereas fat correlated with calorie intake, and histidine and serine with protein intake. Taurine, aspartic acid, cystine, citrulline, urea, creatinine, prealbumin and retinol-binding protein were decreased in malnutrition but were higher than normal due to a loss of renal function. Fourteen variables, less affected by malnutrition, were changed by specific non-nutritional factors. Hemodialysis patients of long standing (1 to 11 years) apart from two patients with recurrent sepsis, were adequately nourished, but those on hemodialysis for less than 15 months, most of whom had previously received peritoneal dialysis, were malnourished. Malnutrition in dialysis patients was due to protein and energy deficiency enhanced by metabolic abnormalities of amino acids. Our study shows that plasma valine is interrelated with other nutritional variables and may be used to assess protein-energy malnutrition.
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PMID:Anthropometry and plasma valine, amino acids, and proteins in the nutritional assessment of hemodialysis patients. 680 21


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