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)

Sepsis is a severe catabolic condition. The loss of skeletal muscle protein mass is characterized by enhanced release of the amino acids glutamine and arginine, which (in)directly affects interorgan arginine and the related nitric oxide (NO) synthesis. To establish whether changes in muscle amino acid and protein kinetics are regulated by NO synthesized by nitric oxide synthase-2 or -3 (NOS2 or NOS3), we studied C57BL6/J wild-type (WT), NOS2-deficient (NOS2-/-), and NOS3-deficient (NOS3-/-) mice under control (unstimulated) and lipopolysaccharide (LPS)-treated conditions. Muscle amino acid metabolism was studied across the hindquarter by infusing the stable isotopes L-[ring-2H5]phenylalanine, L-[ring-2H2]tyrosine, L-[guanidino-15N2]arginine, and L-[ureido-13C,2H2]citrulline. Muscle blood flow was measured using radioactive p-aminohippuric acid dilution. Under baseline conditions, muscle blood flow was halved in NOS2-/- mice (P < 0.1), with simultaneous reductions in muscle glutamine, glycine, alanine, arginine release and glutamic acid, citrulline, valine, and leucine uptake (P < 0.1). After LPS treatment, (net) muscle protein synthesis increased in WT and NOS2-/- mice [LPS vs. control: 13 +/- 3 vs. 8 +/- 1 (SE) nmol.10 g(-1).min(-1) (WT), 18 +/- 5 vs. 7 +/- 2 nmol.10 g(-1).min(-1) (NOS2-/-); P < 0.05 for LPS vs. control]. This response was absent in NOS3-/- mice (LPS vs. control: 11 +/- 4 vs. 10 +/- 2 nmol.10 g(-1).min(-1)). In agreement, the increase in muscle arginine turnover after LPS was also absent in NOS3-/- mice. In conclusion, disruption of the NOS2 gene compromises muscle glutamine release and muscle blood flow in control mice, but had only minor effects after LPS. NOS3 activity is crucial for the increase in muscle arginine and protein turnover during early endotoxemia.
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PMID:NOS3 is involved in the increased protein and arginine metabolic response in muscle during early endotoxemia in mice. 1564 57

Recent studies indicated that prefeeding of a glycine supplemented diet reduces the hepatic inflammatory response and liver damage in sepsis. We investigated the effect of a glycine-enriched infusion on hepatic microcirculatory disturbances and mortality in a rat model of sepsis after the onset of the disease. Male Wistar rats (240 +/- 13 g) underwent cecal ligation and puncture (CLP) or laparotomy (LAP). A glycine (CLP + Gly, n = 24), valine (CLP + Val, n = 24), or sodium chlorid (CLP + Sc, n = 24) infusion was started 2 h after CLP. The LAP group received sodium chloride intravenously (LAP + Sc, n = 18 ). Five hours, 10 h, and 20 h after CLP or LAP intravital microscopy (IVM) was performed to investigate leukocyte-endothelial interaction (LEI) and mean erythrocyte velocity in liver sinusoids (sMEV) and postsinosoidal venules (vMEV). The portal blood flow (PBF), hepatic enzyme liberation, and glycine values in blood were measured. Immunohistochemical staining for ICAM-1 in liver tissue was performed and survival was observed. Glycine values were significantly elevated in the CLP + Gly vs. the CLP + Val and the CLP + Sc group at every timepoint of investigation. Glycine infusion had no beneficial effects on sMEV, vMEV, LEI, hepatic enzyme liberation, and survival. Heart rate and mean arterial pressure remained stable but PBF decreased significantly in all groups 20 h after CLP. Although glycine reduces the hepatic inflammatory response and liver damage in pretreatment of septic rats, there was no effect of intravenous glycine after the onset of sepsis in our experiments. Our animal model does not support the use of glycine in patients.
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PMID:Intravenous glycine after cecal ligation and puncture has no effect on impaired hepatic microperfusion, leukocyte adhesion, and mortality in septic rats. 1579 63

Acute and chronic ischaemic diseases are among the main death reasons and civilized world menace. Branched chain amino acids (BCAAs): valine (Val), leucine (Leu), and isoleucine (Ile) are the main source of nitrogen to glutamine (Gln) and alanine (Ala) synthesis in muscles. In numerous cachexy-producing illnesses such as cancer, sepsis, diverse injuries and heart diseases increased consumption of BCAAs occurs. In myocardial ischemia BCAAs derived from the mobilization of muscle protein may be an important alternative energy substrate for the heart. BCAAs are oxidative energy substrates for the heart and may exert anabolic effects on myocardial protein (8). The aim of our study was to determine branched chain amino acids (BCAAs) concentrations in blood plasma of patients with chronic and acute ischeamic heart disease and to find out changes that those amino acids undergo during the first five days of patients' hospitalization.
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PMID:Branched chain amino acids (BCAAs) in heart diseases (ischaemic heart disease and myocardial infarction). 1614 56

Branched-chain amino acids (BCAAs; valine, leucine, and isoleucine) represent important precursors in the synthesis of glutamine and alanine in the skeletal muscle. Enhanced oxidation of BCAAs can cover the elevated demands of the body on glutamine and alanine during severe illnesses (sepsis, polytrauma, burns). The sufficient supply of the BCAAs in such conditions is facilitated by increased proteolysis in skeletal muscle. However, it can result in muscle wasting and negative protein balance. While concentrations of the BCAAs and alanine are rarely significantly altered, a marked decrease in glutamine concentration, particularly in skeletal muscle, is frequently observed. Glutamine is therefore considered to be a conditional essential amino acid. The manuscript describes the metabolic relations between BCAAs and glutamine, and explains the importance of the recycling of BCAAs and their ketoanalogues between the liver and skeletal muscle. Finally, it is suggested that the favourable effect of glutamine administration on protein metabolism is related to changes in BCAA metabolism.
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PMID:[Glutamine and branched-chain amino acids--practical importance of their metabolic relations]. 1633 56

Various experimental studies conducted in the 1970s demonstrated, at least in the physiological situation, the anabolic and/or anticatabolic properties of branched-chain amino acids (leucine, valine, isoleucine) or their ketoacid derivatives. This led to several clinical studies in the late 1970s and early 1980s that aimed to evaluate the potential benefits of BCAA supplementation in nutritional support of the critically ill. The data on burn, trauma, and sepsis are, however, far from convincing. Besides significant discrepancies in their results and the fact that most of these studies involved very small populations of patients, few of them meet the current standards of therapeutic evaluation. However, some positive results in specific studies suggest that the underlying concept may be correct but that interpretation has been faulty. Indeed, we know now that while the BCAAs possess regulatory properties on protein metabolism, leucine is by far the most potent, while isoleucine and valine are inefficient. However, in the above-mentioned studies, BCAA-supplemented nutrition very frequently supplied almost equivalent amounts of all 3 BCAAs. Moreover, several studies were performed without adequate basal nutritional support, which most probably hampered the correct metabolic utilization of these amino acids. Taken together, these factors mean that the demonstrations of BCAA efficacy were fortunate in the least. In contrast, more recently, leucine was demonstrated to positively affect protein synthesis in an experimental model of sepsis or burn. In parallel, 2 prospective controlled trials of BCAA supplementation in septic patients also demonstrated an improvement in patients' nutritional status and outcome. Thus, we should abandon the concept of BCAA-supplemented nutrition for a more promising leucine-supplemented nutrition that requires further evaluation.
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PMID:Therapeutic use of branched-chain amino acids in burn, trauma, and sepsis. 1636 4

Branched-chain amino acids (BCAA: leucine, isoleucine and valine) are not just structural constituents of proteins, but have ''pharmacologic'' properties, known for several years: BCAA are catabolized mainly in muscle; can be oxidized with energy production, being nitrogen donors for other amino acids; regulate protein synthesis and degradation; modulate metabolism of neuroactive mediators. These properties make the clinical use of BCAA particularly suitable in critical conditions such as liver cirrhosis, sepsis, surgical or nonsurgical trauma, acute renal failure, acute pancreatitis, cancer, in which energy production from conventional substrates is altered and, at the same time, reduction of protein catabolism and enhancement of synthetic processes is advisable. Recently, the changes of plasma aminoacidograms induced by the administration of high-dose BCAA in sepsis have been better detailed: 1) a tendency to normalization of high levels of proline and of other amino acids transported intracellularly by transport system ''A''; 2) less relevant reduction of the levels of other amino acids; 3) increase of the levels of taurine, glutamate and aspartate; more complex interactions with specific amino acids. These changes, and changes of other variables, reconfirm in part some well-known properties of BCAA, and are also objective indicators of an improvement of the metabolic abnormalities of sepsis induced by BCAA administration. In sepsis and in other stress conditions it is recommended to administer, within balanced parenteral nutritional regimens, AA solutions with a 35-50% BCAA concentration.
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PMID:[The branched-chain amino acids]. 1650 46

The metabolic profiles of 14 patients with prolonged abdominal sepsis were analysed on the second day after laparotomy. The profiles of survivors were compared with those of non-survivors who died one to five days after the time of evaluation due to uncontrollable multiple organ failure. In the non-surviving patients plasma glucose and glucagon levels were significantly higher than in surviving patients. The plasma concentrations of phosphoserine, cysteine, valine, phenylalanine, and 3-methylhistidine were found to be significantly increased in non-survivors and their muscle tissue showed significantly decreased concentrations of glutamine, proline and lysine with increases in valine and leucine. A correct classification of non-survivors and survivors could be obtained from the plasma and muscle amino acid concentrations, the highest discriminant power being from muscle glutamine. In severe sepsis metabolic changes correlate with the outcome of the patients, and amino acid metabolism seems to be characterised by low concentrations of muscle glutamine and high levels of the branched chain amino acids possibly indicating an inhibited intracellular glutamine formation in muscle tissue.
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PMID:Metabolic disorders in severe abdominal sepsis: glutamine deficiency in skeletal muscle. 1682 66

Total parenteral nutrition with branched chain amino-acids enriched solutions has been advocated in patients with sepsis and stress because of favourable effects on nitrogen balance, protein synthesis and immune competence. The rationale for the use of BCAA-enriched solutions is based on their potential to correct the plasma amino-acid imbalances seen in these patients. In a 7-day prospective randomised study we investigated the effects on plasma amino-acid concentrations of a standard amino-acid solution (15.6% BCAA) and a branched chain amino-acid enriched solution (50.2% BCAA) in 101 parenterally fed patients with carefully assessed sepsis and/or stress scores. The infusion of the BCAA-enriched solution led to an imbalance of the essential plasma amino-acids. The branched chain amino-acids valine, leucine and isoleucine increased significantly while the non-BCAA essential amino-acids decreased significantly. In the standard solution the non-BCAA-essential amino-acids increased significantly with a slow and insignificant rise in the levels of the branched chain amino-acids. We conclude that infusion of a BCAA enriched TPN formulation induced amino-acid profile derangements that can be considered ill-suited to the achievement of anti-catabolic effects.
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PMID:Effects of infusion of branched chain amino-acids enriched TPN solutions on plasma amino-acid profiles in sepsis and trauma patients. 1683 65

We hypothesized that the dietary threonine demand for the anabolic response may be increased more than that of other essential amino acids during sepsis. Using a flooding dose of either L-[1 -13C]valine or L-[U -13C]threonine, we measured valine and threonine utilization for syntheses of plasma proteins (minus albumin), and wall, mucosal, and mucin proteins of the small intestine in infected (INF; d 2 and d 6 of postinfection) and control pair-fed (PF) rats. At d 2, the protein absolute synthesis rate (ASR) of INF rats was 21% (mucins) to 41% (intestinal wall) greater than that of PF when measured using valine as tracer, and 45% (mucosa) to 113% (mucins) greater than that of PF when measured with threonine as tracer. Plasma protein ASR was higher in INF than in PF rats, reaching 5- to 6-fold the value of PF. The utilization of both amino acid tracers for the protein synthesis was significantly increased by the infection in all compartments studied. The daily increased absolute threonine utilization for protein synthesis in gut wall plus plasma proteins was 446 micromol/d compared with 365 micromol/d for valine, and it represented 2.6 times the dietary threonine intake of rats at d 2. Most changes in protein ASR and threonine utilization observed at d 6 of postinfection were limited. In conclusion, sepsis increased the utilization of threonine for the anabolic splanchnic response. Because this threonine requirement is likely covered by muscle protein mobilization, increasing the threonine dietary supply would be an effective early nutritional management for patients with sepsis.
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PMID:Threonine utilization for synthesis of acute phase proteins, intestinal proteins, and mucins is increased during sepsis in rats. 1758 34

Maple syrup urine disease (MSUD) is a rare inborn error of metabolism, caused by a deficiency in activity of the branched chain alpha-keto acid dehydrogenase impairing the degradation of the branched-chain amino acids (leucine, isoleucine and valine). Classic MSUD usually manifests in the neonatal period with poor feeding, vomiting, lethargy, muscular hypertonicity, seizure, coma and death. Thirteen cases of classic MSUD were diagnosed from 1997-2007 at the Queen Sirikit National Institute of Child Health. All cases presented in the neonatal period. The onset of symptoms ranged from 3 to 20 days (median 8 days). The time taken to make the diagnosis ranged from 18 to 356 days (median 55 days). The diagnosis was accomplished by clinical diagnosis and confirmed by detecting abnormal levels of amino acids in the blood and organic acids in the urine. Clinical manifestations were non-specific such as poor suck, weak cry, drowsiness and seizures. Majority of cases were initially diagnosed as sepsis and/or meningitis. All patients had neurological sequelae and psychomotor retardation. This results show the need for increase awareness of metabolic disorder such as MSUD and the requirement for early detection and treatment to ensure a better outcome.
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PMID:Maple syrup urine disease in Thai infants. 1925 91


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