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)

The use of EN in diabetics is problematic due to the rapid absorption of the nutrients and difficulties in controlling glycemia. The purpose of this study is to evaluate the clinical tolerance and effects of a special diet for patients unable to tolerate glucose on glycemia and insulin requirements, containing 50% of its caloric intake in the form of fats (mainly monounsaturated fatty acids) and a high fibre content. This diet was used on a group of Intensive Care patients with stress diabetes, comparing it to a high protein diet in terms of Nitrogen Balance and evolution of circulating proteins. 35 patients admitted to Intensive Care with traumas or sepsis were studied. The patients received EN for a period of 14 days. They were divided into two groups at random. Group A received a high protein diet and Group B the special diet for patients with intolerance to glucose. In Group A, the levels of glycemia and insulin requirements were significantly higher than those of Group B. There were no significant differences in albumin, transferrin, prealbumin and RBP levels in both groups. Cholesterol levels remained normal, although on day 14 they were higher in Group B patients. Group A patients had higher triglyceride levels. The nitrogen balance was only higher on days 6 and 7 in Group A patients, with and accumulated Balance for the 14 days of 11.54 +/- 3.5 g. In Group A compared to 6.24 +/- 2.63 g. in Group B. Clinical tolerance to the diet was satisfactory, with the usual problems in critical patients.
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PMID:[Experience with an enteral diet with fiber and a high fat content in ICU patients with glucose intolerance]. 132 77

The objective of this study was to evaluate the safety and the effect of recombinant exogenous growth hormone (GH) on nitrogen production in patients with severe sepsis. It was designed as a prospective, randomized, placebo-controlled trial, and performed in the medical intensive care unit of a university hospital. Twenty patients admitted with septic shock and receiving standard parenteral nutrition served as subjects. Treatment consisted of GH 0.1 mg/kg/day or placebo administered as continuous intravenous infusion on the second, third, and fourth days after admission. The study period was eight days. During GH administration, nitrogen production decreased significantly in the GH group and increased in controls (p < 0.01). Nitrogen balance became slightly positive in the GH group during treatment: 1.2 +/- 6.4 versus controls -3.7 +/- 3.8 g/day (day 3) (p < 0.05). Within 24 hours after cessation of treatment, differences between GH and controls disappeared. 3-Methylhistidine excretion as a measure of absolute muscle breakdown declined during the study period, but did not differ between groups. The levels of insulin, insulinlike growth factor 1, glycerol, free fatty acids, and beta-hydroxybutyrate increased during treatment. Despite continuous intravenous administration, GH levels gradually declined during the 3 treatment days, indicating increased metabolic clearance. Side effects other than insulin resistance were not observed. Growth hormone administration reduces nitrogen production and improves nitrogen balance in patients with severe sepsis. These effects are not sustained after cessation of treatment.
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PMID:Effects of recombinant human growth hormone in patients with severe sepsis. 146 18

The ideal energy substrate for critically ill patients receiving total parenteral nutrition (TPN) remains controversial. While glucose has been proved to have nitrogen sparing properties in postoperative patients, critically ill patients tolerate glucose loads poorly and fat appears to be an obligatory fuel in sepsis. Furthermore, it is not yet certain whether the changes in whole body protein metabolism induced by critical illness are influenced by the nature of the TPN provided. This study was conducted on patients admitted to a surgical intensive care unit (SICU) who fulfilled the criteria of requiring TPN and mechanical ventilation for at least four days. Patients were randomized to receive either glucose (G) or equicaloric proportions of glucose and lipid (GF) as an intravenous energy source. TPN was commenced early, within 24-48 hr of trauma or surgery and admission to the ICU. Nonprotein calorie intake was 125% of calculated basal energy expenditure. Nitrogen balance was calculated from 24-hr urinary urea excretion. Protein synthesis, turnover, and catabolism were measured on Day 4 of the study using an established radiolabeled C14-leucine technique. Degree of sepsis and illness were calculated using published scores. Fifty patients entered the trial but 32 were excluded by Day 4. Of the 18 patients completing an initial four day study, eight went on to complete a second study on the alternative regimen--a total of 26 studies (14 G, 12 GF). Net protein synthesis was achieved in 18 studies (12 G, 6 FG) and positive nitrogen balance by Day 4 in 22 studies. Four patients on the G regimen were withdrawn due to glucose intolerance while none of the patients on GF developed glucose intolerance or hyperlipidaemia. Both whole body protein synthesis and catabolism correlated significantly with degree of sepsis. The type of TPN fuel used, G and GF, did not appear to influence whole body protein dynamics, both regimens achieving greatly improved whole body protein kinetics.
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PMID:The effect of fuel source on amino acid metabolism in critically ill patients. 174 Sep 40

Pseudomonas aeruginosa alkaline proteinase, which is a zinc-dependent bacterial endopeptidase, preferentially hydrolyzed Boc-Val-Leu-Lys-methylcoumarylamide (MCA) which was originally designed as a specific substrate of plasmin, a plasma serine proteinase. The hydrolytic capacity was resistant to tosyl-lysine chloromethylketone at a concentration as high as 1 mM, but was blocked by a treatment with metal chelator such as o-phenanthroline at the concentration of 5 mM. Kinetic parameters of the amidolytic reaction were Km = 21 microM, kcat = 0.067 s-1 and kcat/Km = 3190 M-1 s-1. A synthetic peptide inhibitor which bore a possible ligand for zinc atom at the carboxy terminal was designed. This inhibitor, Ac-Val-Leu-Lys-4-mercaptoanilide, blocked the amidolytic activity of the pseudomonal alkaline proteinase in a competitive manner with the dissociation constant (Ki) value of 24 microM. The results imply that P. aeruginosa alkaline proteinase must be an unusual zinc-dependent 'C (COOH)-type' endopeptidase, which hydrolyzes the peptide bond of certain amino acid residues at the carboxyl group side by specific recognition, like serine- and cysteine-proteinases. In comparison, P. aeruginosa elastase which is a typical 'N (NH2)-type' metalloproteinase did not hydrolyze all of the commercially available peptide-MCA substrates tested at the present study. P. aeruginosa alkaline proteinase also hydrolyzed natural substrates of plasmin, such as fibrin and fibrinogen, with similar specific activities to plasmin. The susceptible subunits of fibrinogen were the A-alpha and B-beta ones, in this order. P. aeruginosa alkaline proteinase also exhibited an anti-coagulant activity in human plasma attributed to the direct fibrinogenolytic function. Such potential anti-coagulant capacity of the P. aeruginosa alkaline proteinase might explain, at least partly, the most characteristic pathologic feature of the P. aeruginosa septicemia, hemorrhagic lesions with lacking thrombi (Fetzer, A.E. et al. (1967) Am. Rev. Respirat. Dis. 96, 1121-1130).
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PMID:Pseudomonas aeruginosa alkaline proteinase might share a biological function with plasmin. 182 96

Pharmacologic therapy designed to block adrenergic activity or alter hormonal milieu may modulate energy and protein metabolism in stress. The metabolic effects of propranolol (beta adrenergic receptor blocker) in sepsis was investigated in 22 well-nourished rats that underwent superior vena caval cannulation, cecal ligation, and puncture. Animals were randomly assigned to receive either a continuous infusion of 0.7 mg/day of propranolol combined with parenteral nutrition (n = 11) or parenteral nutrition alone (n = 11). Both groups received isocaloric, isonitrogenous, isovolemic, parenteral nutrition post-operatively for 24 hr. Nitrogen balance was better for the propranolol group than for the control group (+743 +/- 84 mg/kg/day versus +300 +/- 63 mg/kg/day, respectively, P less than 0.05). A significant difference between the pharmacologic therapy and control groups was noted for urinary 3-methylhistidine excretion versus control (0.99 +/- 0.08 micrograms/kg/day versus 7.5 +/- 0.37 micrograms/kg/day, respectively, P less than 0.01). Measured energy expenditure was similar for both pharmacologic therapy and control groups (149 +/- 20 kcal/kg/day versus 134 +/- 11 kcal/kg/day, respectively, P = N.S.). No statistically significant difference was demonstrated for 24-hr survival between propranolol and control groups (73 and 64%, respectively). Continuous, low-dose propranolol promotes nitrogen retention and decreases 3-methylhistidine excretion without altering energy expenditure in parenterally fed septic rats.
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PMID:Effect of propranolol on nitrogen and energy metabolism in sepsis. 210 45

To evaluate the efficacy of supplemental arginine with nutritional support in the presence of sepsis, eighty-eight gastrostomized female Hartley guinea pigs were implanted with osmotic pumps effusing an Eschericia coli/Staphylococcus aureus mixture. Animals were randomized and infused for two weeks with isocaloric and isovolumetric diets containing 0%, 2%, 4%, or 6% supplemental arginine as arginine hydrochloride. Survival was 12/22 (54%) in 0%, 9/22 (41%) in 2% and 4%, and 2/22 (9%) in 6%. Analysis by chi-square test of independence was significant (p = 0.0141) with 6% survival lower than the others. Median survival was 11 days in 0%, 8 days in 2% and 6%, and 9 days in 4%. Median survival was longer in 0% than in 2% or 6% (Kruskal-Wallis ANOVA: p = 0.02). Nitrogen balance was significantly lower in 6% compared to 0% on days 2 through 10, and lower than 2% and 4% on days 6 and 9. Nitrogen balance was higher in 0% than in 2% on days 4, 6, 10, and 13. Serum albumin and C3 were lower in all experimental groups than normal controls (ANOVA: p = 0.01). Comparison of liver, spleen, adrenals, gastrocnemius, and carcass weights, cell-mediated immunity as determined by contact sensitivity to DNFB, and transferrin showed no significant differences. There was a positive dose-response effect seen amongst the experimental groups for the amino acids arginine, ornithine, and citrulline in relation to the amount of supplemental arginine. This study suggests that dietary arginine supplementation does not enhance survival in a guinea pig model of established peritonitis.
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PMID:Arginine supplementation and its effect on established peritonitis in guinea pigs. 211 35

Administration of extra branched chain amino acids (BCAA) has been associated with a nitrogen sparing effect in septic and traumatized patients. Whether nitrogen sparing is associated with decreased morbidity and mortality rates is unknown. We therefore undertook a prospective, randomized, double blind trial investigating the effects of BCAA enrichment of a total parenteral nutrition (TPN) regimen on nitrogen balance, 3-methylhistidine excretion, morbidity as evidenced by disturbances in organ function, severity of sepsis and mortality. One hundred and one patients entered the study; 52 received a standard TPN solution and 49 a BCAA-enriched solution. Both groups received 30 kcal kg-1 body-weight, 15 per cent fat calories and 0.17 g nitrogen kg-1 body-weight. In the BCAA-enriched group, patients received 0.56 g BCAA kg-1 body-weight (50.2 per cent BCAA). Standard group patients received 0.18 g BCAA kg-1 body-weight (15.6 per cent BCAA). Nitrogen balances and 3-methylhistidine excretion were not significantly different between groups. Although morbidity scores tended to decrease during the study no difference was observed between groups. Mortality (early or late), sepsis or stress-related, did not differ significantly between groups. We were not able to confirm the reported beneficial effects of BCAA-enriched TPN solutions for use in septic and traumatized patients.
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PMID:Effect of branched chain amino acid enrichment of total parenteral nutrition on nitrogen sparing and clinical outcome of sepsis and trauma: a prospective randomized double blind trial. 211 8

Vibrio vulnificus, an etiologic agent of wound infections and septicemia in humans, elaborates a metalloprotease which is known to be an important virulence factor of the Vibrio. The proteolytic activity of V. vulnificus metalloprotease (VVP) toward casein and elastin was inhibited by alpha 2-macroglobulin (alpha 2 M) at the molar ratio of 1:1, although partial activity was maintained. Permeability-enhancing and hemorrhagic activities were also inhibited, but the peptidase activity toward Z-Gly-Phe-NH2 was not reduced, even by an excess amount of alpha 2 M. VVP formed a complex with alpha 2 M through cleavage of the bait regions of all four alpha 2 M subunits and elicitation of conformational change of the alpha 2 M molecule, which resulted in entrapment of VVP in the alpha 2 M molecule. The peptidase activity of alpha 2 M-VVP complex was inhibited by low-molecular-weight inhibitors such as phosphoramidon, but IgG antibody against VVP failed to neutralize its peptidase activity. Of human plasma proteins, alpha 2 M was the only inhibitor for VVP. These findings indicate that VVP produced during V. vulnificus infection is inactivated by plasma alpha 2 M that leaks from the vascular system.
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PMID:Inhibitory effect of alpha 2-macroglobulin on Vibrio vulnificus protease. 247 26

The metabolic alterations, nutritional and metabolic assessment, and nutritional requirements of critically ill patients are discussed, and parenteral nutrition support therapies are reviewed. Physiological alterations in the metabolism of the injured or septic patient are mediated through the interactions of neuroendocrine, cardiovascular, toxic, and starvation responses. These responses cause mobilization of nutritional substrates in an effort to maintain vital organ function and immune defenses. A patient's nutritional status can be determined from anthropometric measurements, creatinine excretion rate, and evaluations of protein stores and immune reserves and function; body weight is a poor indicator. Nitrogen-balance calculations are also useful for determining the adequacy of nutritional intake and the degree of metabolic stress. Early assessments of nutritional status may assist in identifying those patients for whom nutritional support interventions are needed. Nutritional requirements are altered by the metabolic responses to injury and sepsis. Studies suggest that use of nutrient solutions enriched for branched-chain amino acids may enhance nitrogen retention and that energy expenditures in injured or septic patients are only moderately elevated. Most nonprotein calories in parenteral nutrient solutions are provided as glucose, but lipids are an important source of energy in the critically ill patient who has high energy requirements or carbohydrate intolerance; however, clearance of lipids may be decreased. Fluid, electrolyte, and mineral status must be evaluated frequently. Critically ill patients have unique nutritional requirements, and parenteral nutrition support therapies for these patients are being investigated and refined.
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PMID:Parenteral nutrition in the critically ill patient. 250 29

A prospective, randomized trial was undertaken to compare the nutritional efficacy in surgical stress of a standard amino acid solution and two branched chain-enriched amino acid solutions: one enriched primarily with valine, the other with leucine. The study comprised 37 patients in the surgical intensive care unit who received isocaloric, isonitrogenous parenteral nutrition started within 24 hours of the onset of major operation, injury, or sepsis. Nitrogen retention was marginally but statistically significantly better on days 5, 7, and 10 in both groups of patients receiving the branched chain-enriched solutions, but differences in cumulative nitrogen balance were not statistically significant. Amino acid composition appeared to be important in that the group receiving the leucine-enriched solution appeared to maintain hepatic protein synthesis better (as manifest by higher short-turnover plasma protein concentrations) and required less exogenous insulin to maintain euglycemia. Improved outcome was not seen in the groups receiving the branched chain-enriched solutions.
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PMID:Branched chain amino acid-enriched solutions in the septic patient. A randomized, prospective trial. 307 94


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