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 identification of plasma markers of the course of the acute respiratory distress syndrome (ARDS) is needed to improve its treatment and to further advance the development of new therapeutic agents. The status of markers of lung injury in ARDS is reviewed and some new potential markers are proposed. This study focused on plasma amino acids, related amino compounds, and catecholamine levels during the acute phase of endotoxin-induced lung injury in 8 sheep characterized by the onset of pulmonary edema caused by increased microvascular permeability. A number of significant changes from baseline values were found. During the sixth hour of a 12-hour period of endotoxin infusion, norepinephrine, epinephrine, and alanine levels increased whereas the isoleucine level decreased. During the sixth hour of the immediate postendotoxin period, the taurine level increased while the levels of arginine, citrulline, glycine, isoleucine, methionine, ornithine, serine, threonine, and tryptophan decreased. These findings are compared with prior studies in human subjects detailing the amino acid profile characteristic of advanced sepsis. We conclude that the present profile of catecholamine and amino acid changes during endotoxemia in sheep deserves further study in human subjects to determine its significance as a marker of the early stage of ARDS.
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PMID:A profile of amino acid and catecholamine levels during endotoxin-induced acute lung injury in sheep: searching for potential markers of the acute respiratory distress syndrome. 896 Jun 37

This study was designed to investigate the effects of preinfusion with total parenteral nutrition (TPN) using fish-oil (FO) versus safflower-oil (SO) emulsion as fat sources on hepatic lipids, plasma amino-acid profiles, and inflammatory-related mediators in septic rats. Normal rats, with internal jugular catheters, were assigned to two different groups and received TPN. TPN provided 300 kcal. kg(-1). d(-1), with 40% of the non-protein energy as fat. All TPN solutions were isonitrogenous and identical in nutrient composition except for the fat emulsion, which was made of SO or FO. After receiving TPN for 6 d, each group of rats was further divided into control and sepsis subgroups. Sepsis was induced by cecal ligation and puncture; control rats received sham operation. All rats were classified into four groups as follows: FO control group (FOC; n = 7), FO sepsis group (FOS; n = 8), SO control group (SOC; n = 8), and SO sepsis group (SOS; n = 9). The results of the study demonstrated that plasma concentrations of triacylglycerol and non-esterified fatty acids did not differ between the FO and SO groups, regardless of whether the animals were septic. SOS had significantly higher total lipids and cholesterol content in the liver than did the SOC group. The FOS group, however, showed no difference from the FOC group. Plasma leucine and isoleucine levels were significantly lower in the SOS group than in the SOC group, whereas no difference in these two amino acids was observed between the FOC and FOS groups. Plasma arginine levels were significantly lower in both septic groups than in the groups without sepsis when either FO or SO was infused. Plasma glutamine levels, however, did not differ across groups. No differences in interleukin-1beta, interleukin-6, tumor necrosis factor-alpha, or leukotriene B(4) concentrations in peritoneal lavage fluid were observed between the two septic groups. These results suggest that catabolic reaction in septic rats preinfused with FO is not as obvious as those preinfused with SO. Compared with SO emulsion, TPN with FO emulsion prevents liver fat accumulation associated with sepsis. However, parenterally administered FO had no beneficial effect in lowering cytokines and LTB(4) levels in peritoneal lavage fluid in septic rats induced by cecal ligation and puncture.
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PMID:Effects of parenteral infusion with fish-oil or safflower-oil emulsion on hepatic lipids, plasma amino acids, and inflammatory mediators in septic rats. 1075 71

This study was designed to investigate the effects of preinfusion with total parenteral nutrition (TPN) using medium-chain triglycerides (MCT) versus safflower oil (SO) emulsion as fat sources on hepatic lipids, plasma amino acid profiles, and inflammatory-related mediators in septic rats. Normal rats, with internal jugular catheters, were divided into two groups and received TPN. TPN provided 300kcal/kg/day with 40% of the non-protein energy provided as fat. All TPN solutions were isonitrogenous and identical in nutrient composition except for the fat emulsion, which was made of SO or a mixture of MCT and soybean oil (9:1) (MO). After receiving TPN for 6 days, each group of rats was further divided into control and sepsis subgroups. Sepsis was induced by cecal ligation and puncture, whereas control rats received sham operation. All rats were classified into four groups as follows: MCT control group (MOC, n= 8), MCT sepsis group (MOS, n= 8), safflower oil control group (SOC, n= 8), and safflower oil sepsis group (SOS, n= 11). The results of the study demonstrated that the MOS group had lower hepatic lipids than did the SOS group. Plasma leucine and isoleucine levels were significantly lower in the SOS than in the SOC group, but no differences in these two amino acids were observed between the MOC and MOS groups. Plasma arginine levels were significantly lower in septic groups than in those without sepsis despite whether MCT or safflower oil was infused. Plasma glutamine and alanine levels, however, did not differ between septic and non-septic groups either in the SO or MO groups. No differences in interleukin-1b, interleukin-6, tumor necrosis factor-alpha, and leukotriene B(4)concentrations in peritoneal lavage fluid were observed between the two septic groups. These results suggest that catabolic reaction is septic rats preinfused MCT is not as obvious as those preinfused safflower oil. Compared with safflower oil, TPN with MCT administration has better effects on reducing sepsis-induced liver fat deposition. Preinfusion with MCT before sepsis, however, had no effect on inflammatory-related cytokines or leukotriene in peritoneal lavage fluid. In addition, plasma arginine appears to be a more sensitive indicator than glutamine for septic insult.
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PMID:Effects of parenteral infusion with medium-chain triglycerides and safflower oil emulsions on hepatic lipids, plasma amino acids and inflammatory mediators in septic rats. 1086 29

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

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

Vascular permeability plays a key role in a wide array of life-threatening and sight-threatening diseases. Vascular endothelial growth factor can increase vascular permeability. Using a model system for nonproliferative diabetic retinopathy, we found that pigment epithelium-derived factor (PEDF) effectively abated vascular endothelial growth factor-induced vascular permeability. A 44-amino acid region of PEDF was sufficient to confer the antivasopermeability activity. Additionally, we identified four amino acids (glutamate-101, isoleucine-103, leucine-112, and serine-115) critical for this activity. PEDF, or a derivative, could potentially abate or restore vision loss from diabetic macular edema. Furthermore, PEDF may represent a superior therapeutic approach to sepsis-associated hypotension, nephrotic syndrome, and other sight-threatening and life-threatening diseases resulting from excessive vascular permeability.
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PMID:Identification of the antivasopermeability effect of pigment epithelium-derived factor and its active site. 1509 82


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