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)

Plasma albumin is well known to decrease in response to inflammation. The rate of albumin synthesis from both liver and plasma was measured in vivo by use of a large dose of L-[(2)H(3)-(14)C]valine in rats injected intravenously with live Escherichia coli and in pair-fed control rats during the acute-phase period (2 days postinfection). The plasma albumin concentration was reduced by 50% in infected rats compared with pair-fed animals. Infection induced a fall in both liver albumin mRNA levels and albumin synthesis relative to total liver protein synthesis. However, absolute liver albumin synthesis rate (ASR) was not affected by infection. In plasma, albumin fractional synthesis rate was increased by 50% in infected animals compared with pair-fed animals. The albumin ASR estimated in the plasma was similar in the two groups. These results suggest that hypoalbuminemia is not due to reduced albumin synthesis during sepsis. Moreover, liver and plasma albumin ASR were similar. Therefore, albumin synthesis measured in the plasma is a good indicator of liver albumin synthesis.
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PMID:Synthesis rate of plasma albumin is a good indicator of liver albumin synthesis in sepsis. 1091 22

Although reports of decreased plasma taurine in trauma, sepsis and critical illness are available, very little is known about the relationships among changes in plasma taurine, other amino acid levels and metabolic variables. We analyzed a large series of plasma amino acid profiles obtained in trauma patients with sepsis who were undergoing total parenteral nutrition. The correlations between plasma taurine, other amino acid levels, parenteral substrate doses and metabolic and cardiorespiratory variables were assessed by regression analysis. Post-traumatic hypotaurinemia was followed by partial recovery toward less abnormal values when sepsis developed. Levels of taurine were directly and significantly related to levels of glutamate, aspartate, beta-alanine and phosphoethanolamine (and unrelated to other amino acids). Levels of these amino acids increased simultaneously with increasing doses of leucine, isoleucine and valine in total parenteral nutrition. Decreasing taurine was associated with increasing lactate, arteriovenous O(2) concentration difference and respiratory index, and with decreasing cholesterol and cardiac index. These results characterize the relationships between plasma taurine and other amino acid levels in sepsis, provide evidence of amino acid interactions that may support taurine availability and show more severe decreases in plasma taurine with the worsening of metabolic and cardiorespiratory patterns.
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PMID:The relationship between plasma taurine and other amino acid levels in human sepsis. 1095 16

This study was designed to investigate the effects of dietary fish oil on survival rates, plasma amino acid profiles, and inflammatory-related mediators in diabetic rats with sepsis. Diabetes mellitus (DM) was induced in rats by streptozotocin. The DM rats were maintained for 4 weeks on medium fat (10%, w/w) diets containing either fish oil or safflower oil. After that, sepsis was induced by cecal ligation and puncture (CLP). There were 2 groups in this study: fish oil sepsis group (FOS) and safflower oil sepsis group (SOS). The survival rate was observed after CLP. Also, changes of the amino acid pattern as well as interleukin (IL)-1 beta, tumor necrosis factor (TNF)-alpha, prostaglandin (PG) E(2)at 6, 12, and 24 h after CLP were investigated. The results demonstrated that survival rates were not significantly different between the 2 groups. Plasma arginine levels were significantly lower in sepsis groups than that in the DM-chow group, regardless of whether the diabetic rats were fed fish oil or safflower oil. No significant differences were observed in plasma valine, leucine, isoleucine, glutamine, or arginine concentrations between the FOS and SOS groups at different time points. Concentrations of IL-1 beta in peritoneal lavage fluid (PLF) at 6 h and TNF-alpha at 6 h as well as at 12 h after CLP in the FOS group were significantly higher than those in the SOS group. PGE(2)levels in PLF, by contrast, were lower in the FOS group at 6 and 12 h after CLP than in the SOS group. These results suggest that differences in IL-1 beta, TNF-alpha, and PGE(2)levels in PLF in the early period of sepsis did not influence the survival rates and plasma amino acid profiles of the FOS and SOS groups. Compared with safflower oil, feeding diabetic rats with fish oil had no beneficial effects on survival rates and muscle protein breakdown. The immunologic impact of dietary n-3 polyunsaturated fatty acids on diabetic rats with sepsis requires further investigation.
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PMID:Effects of dietary fish oil on survival rate, plasma amino acid pattern, and inflammatory-related mediators in diabetic rats with sepsis. 1103 Oct 68

The branched-chain amino acids (BCAAs; valine, isoleucine, and leucine) are the major nitrogen source for glutamine and alanine synthesis in muscle. Synthesis of glutamine, alanine, and BCAA use is activated in critical illnesses such as in sepsis, cancer, and trauma. The use of glutamine often exceeds its synthesis, resulting in the lack of glutamine in plasma and tissues. In critical illness, resynthesis of BCAA from branched-chain keto acids is activated, particularly in hepatic tissue. The BCAA released to circulation may be used for protein synthesis or synthesis of alanine and glutamine. Glutamine and/or alanine infusion has an inhibitory effect on the breakdown of body proteins and decreases BCAA catabolism in postabsorptive control, endotoxemic, and irradiated rats. Decreased protein breakdown also was observed when glutamine synthesis was activated by ammonia infusion. In conclusion some favorable effects of BCAA supply can be explained by its role in the synthesis of glutamine and some positive effects of glutamine exogenous supply can be explained by its effect on metabolism of BCAA.
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PMID:Relation between glutamine, branched-chain amino acids, and protein metabolism. 1184 43

The mechanism by which glutamine produces a favorable effect in the treatment of sepsis, injury, burns and abdominal irradiation is not completely understood. The main aim of this study was to evaluate the effect of alanyl-glutamine (AlaGln) administration on the metabolism of proteins in irradiated rats. The rats were exposed to whole-body irradiation (8Gy) and then fed intragastrically with a mixture of glucose and amino acids either with AlaGln or without AlaGln. At 48 hours after irradiation, parameters of whole-body protein metabolism and DNA synthesis in intestinal mucosa were investigated using a primed, continuous infusion of [1-14C]leucine and [3H]thymidine. In addition, we evaluated the effect of irradiation and AlaGln on gut morphology, blood count and amino acid concentrations in blood plasma and skeletal muscle. Control rats were not irradiated but were given identical treatment. An increase in whole-body leucine oxidation, and insignificant changes in whole-body proteolysis and in protein synthesis were observed after irradiation. In irradiated rats we observed a decrease in muscle glutamine concentration, a decrease in protein synthesis in jejunum, colon and heart, and an increase in synthesis of proteins of blood plasma and spleen. Morphological examination and measurement of DNA synthesis failed to demonstrate any favorable effect of AlaGln supplementation on irradiated gut. However, administration of AlaGln resulted in a decrease in whole-body proteolysis and leucine oxidation which caused an increase in the fraction of leucine incorporated into the pool of body proteins. We conclude that the data obtained demonstrate that irradiation induces metabolic derangement associated with increased oxidation of essential branched-chain amino acids (valine, leucine and isoleucine) and that these disturbances can be ameliorated by administration of AlaGln.
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PMID:Effect of alanyl-glutamine on leucine and protein metabolism in irradiated rats. 1202 76

Branched chain organic acidurias are a group of disorders that result from an abnormality of specific enzymes involving the catabolism of branched chain amino acids (leucine, isoleucine, valine). Maple syrup urine disease (MSUD), isovaleric acidaemia (IVA), propionic aciduria (PA) and methylmalonic aciduria (MMA) represent the most commonly encountered abnormal organic acidurias. All these four disorders present in neonates as a neurologic distress of the intoxication type with either ketosis or ketoacidosis and hyperammonaemia. There is a free interval between birth and clinical symptoms. MMA, PA and IVA present with a severe dehydration, leuconeutropenia and thrombopenia which can mimic sepsis. All these disorders can be diagnosed by identifying acylcarnitine and other organic acid compounds in plasma and urine by gas chromatography mass spectrometry or tandem MS-MS. These disorders are amenable to treatment by removing toxic compounds and by using special diets and carnitine.
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PMID:Branched-chain organic acidurias. 1206 39

Bacterial infection alters whole-body protein homeostasis. Although immune cells are of prime importance for host defense, the effect of sepsis on their protein synthesis rates is poorly documented. We analyzed protein synthesis rates in rat primary lymphoid tissues and circulating lymphocytes after infection. Male Sprague-Dawley rats were studied 1, 2, 6 or 10 d after an intravenous injection of live Escherichia coli. Control healthy rats consumed food ad libitum (d 0) or were pair-fed to infected rats. Protein synthesis was quantified using a flooding dose of L-(4,4,4-(2)H(3))valine. Sepsis induced a delayed increase in total blood leukocytes and a rapid and persistent inversion of the counts. Basal fractional rates of protein synthesis (ks) were 117, 73 and 29%/d in bone marrow, thymus and circulating lymphocytes, respectively. Pair-feeding strongly depressed the absolute protein synthesis rates (ASR) of bone marrow (d 2 and 10) and thymus (d 2-10). The infection per se increased bone marrow, thymus and circulating lymphocyte ks but at various postinfection times. It decreased bone marrow (d 1) and thymus (d 1 and 2) ASR but increased lymphocyte (d 2 and 10) and bone marrow (d 10) ASR. Our results reflect the deleterious effect of anorexia on primary lymphoid tissues. The host defense against bacterial infection exhibited time- and tissue-dependent modifications of protein synthesis, indicating that blood lymphocyte protein data are not representative of the immune system as a whole. Optimization of nutritional supports would be facilitated by including protein synthesis measurements of the immune system.
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PMID:Bacterial infection affects protein synthesis in primary lymphoid tissues and circulating lymphocytes of rats. 1209 87

Dyskeratosis congenita (DKC) is a rare inherited disease characterized by the triad of abnormal skin pigmentation, nail dystrophy, and mucosal leukoplakia. Recent studies demonstrated mutations in the DKC1 gene encoding a protein named dyskerin, which is a component of human telomerase. In addition to the hypothesized function of pseudouridination in rRNA biosynthesis, ribosomal subunit assembly, and/or centromere/ microtubule binding, lower levels of telomerase activity in cells from patients with X-linked DKC have been observed. We report the mutation analysis of a Taiwanese family with X-linked DKC. The patient was a 19-year-old man who presented with progressive reticulate hyperpigmentation, nail dystrophy, alopecia, leukoplakia of the tongue, and pancytopenia. He died of enterocolitis and Escherichia coli sepsis at the age of 20 years. Only his mother's DNA was available for mutation analysis, which revealed a nucleotide transition of C to T (1058 C --> T), a hotspot mutation in DKC, resulting in an amino acid change from alanine to valine (A353V) in the DKC1 gene. Recent advances in the research of telomerase and its implications in the human aging process and cancer are discussed.
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PMID:DKC1 gene mutation in a Taiwanese kindred with X-linked dyskeratosis congenita. 1251 20

Many bacterial pathogens secrete proteins that activate host trypsinogen-like enzyme precursors, most notably the proenzymes of the blood coagulation and fibrinolysis systems. Staphylococcus aureus, an important human pathogen implicated in sepsis and endocarditis, secretes the cofactor staphylocoagulase, which activates prothrombin, without the usual proteolytic cleavages, to directly initiate blood clotting. Here we present the 2.2 A crystal structures of human alpha-thrombin and prethrombin-2 bound to a fully active staphylocoagulase variant. The cofactor consists of two domains, each with three-helix bundles; this is a novel fold that is distinct from known serine proteinase activators, particularly the streptococcal plasminogen activator streptokinase. The staphylocoagulase fold is conserved in other bacterial plasma-protein-binding factors and extracellular-matrix-binding factors. Kinetic studies confirm the importance of isoleucine 1 and valine 2 at the amino terminus of staphylocoagulase for zymogen activation. In addition to making contacts with the 148 loop and (pro)exosite I of prethrombin-2, staphylocoagulase inserts its N-terminal peptide into the activation pocket of bound prethrombin-2, allosterically inducing functional catalytic machinery. These investigations demonstrate unambiguously the validity of the zymogen-activation mechanism known as 'molecular sexuality'.
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PMID:Staphylocoagulase is a prototype for the mechanism of cofactor-induced zymogen activation. 1452 51

The aim of this experiment was to clarify whether an amino acid supplement could enhance the therapeutic effect of vitamin B2 (riboflavin 5'-sodium phosphate; purity > 97%) in mice with lipopolysaccharide-induced shock. Six hours after injection of a lethal dose of lipopolysaccharide, treatment (6-h i.v. infusion) was commenced. All mice died in the groups treated with saline or aminolevane (an amino acids mixture used to treat hepatopathy); however, the survival rates in the vitamin B2 (10 mg/kg/6 h) and vitamin B2 plus aminolevane groups were 45% (P < 0.05) and 80% (P < 0.05), respectively. Valine (200 mg/kg/6 h) alone had little effect on the survival rate (10%), but the combination of vitamin B2 (10 mg/k/g/6 h) and valine was highly effective (80%, P < 0.05). Clinical trials of vitamin B2 plus amino acids for the treatment of patients with sepsis would appear to be warranted.
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PMID:Potentiation by amino acid of the therapeutic effect of highly purified vitamin B2 in mice with lipopolysaccharide-induced shock. 1518 80


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