Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Burn trauma produces significant fluid shifts that, in turn, reduce cardiac output and tissue perfusion. Treatment approaches to major burn injury include administration of crystalloid solutions to correct hypovolemia and to restore peripheral perfusion. While this aggressive postburn volume replacement increases oxygen delivery to previously ischemic tissue, this restoration of oxygen delivery is thought to initiate a series of deleterious events that exacerbate ischemia-related tissue injury. While persistent hypoperfusion after burn trauma would produce cell death, volume resuscitation may exacerbate the tissue injury that occurred during low flow state. It is clear that after burn trauma, tissue adenosine triphosphate (ATP) levels gradually fall, and increased adenosine monophosphate (AMP) is converted to hypoxanthine, providing substrate for xanthine oxidase. These complicated reactions produce hydrogen peroxide and superoxide, clearly recognized deleterious free radicals. In addition to xanthine oxidase related free radical generation in burn trauma, adherent-activated neutrophils produce additional free radicals. Enhanced free radical production is paralleled by impaired antioxidant mechanisms; as indicated by burn-related decreases in superoxide dismutase, catalase, glutathione, alpha tocopherol, and ascorbic acid levels. Burn related upregulation of inducible nitric oxide synthase (iNOS) may produce peripheral vasodilatation, upregulate the transcription factor nuclear factor kappa B (NF-kappaB), and promote transcription and translation of numerous inflammatory cytokines. NO may also interact with the superoxide radical to yield peroxynitrite, a highly reactive mediator of tissue injury. Free radical mediated cell injury has been supported by postburn increases in systemic and tissue levels of lipid peroxidation products such as conjugated dienes, thiobarbituric acid reaction products, or malondialdehyde (MDA) levels. Antioxidant therapy in burn therapy (ascorbic acid, glutathione, N-acetyl-L-cysteine, or vitamins A, E, and C alone or in combination) have been shown to reduce burn and burn/sepsis mediated mortality, to attenuate changes in cellular energetics, to protect microvascular circulation, reduce tissue lipid peroxidation, improve cardiac output, and to reduce the volume of required fluid resuscitation. Antioxidant vitamin therapy with fluid resuscitation has also been shown to prevent burn related cardiac NF-kappaB nuclear migration, to inhibit cardiomyocyte secretion of TNF-alpha, IL-1beta, and IL-6, and to improve cardiac contractile function. These data collectively support the hypothesis that cellular oxidative stress is a critical step in burn-mediated injury, and suggest that antioxidant strategies designed to either inhibit free radical formation or to scavage free radicals may provide organ protection in patients with burn injury.
 ...
PMID:Free radicals and lipid peroxidation mediated injury in burn trauma: the role of antioxidant therapy. 1282 Dec 84

Skeletal muscle disuse with space-flight and ground-based models (e.g., hindlimb unloading) results in dramatic skeletal muscle atrophy and weakness. Pathological conditions that cause muscle wasting (i.e., heart failure, muscular dystrophy, sepsis, COPD, cancer) are characterized by elevated "oxidative stress," where antioxidant defenses are overwhelmed by oxidant production. However, the existence, cellular mechanisms, and ramifications of oxidative stress in skeletal muscle subjected to hindlimb unloading are poorly understood. Thus we examined the effects of hindlimb unloading on hindlimb muscle antioxidant enzymes (e.g., superoxide dismutase, catalase, glutathione peroxidase), nonenzymatic antioxidant scavenging capacity (ASC), total hydroperoxides, and dichlorohydrofluorescein diacetate (DCFH-DA) oxidation, a direct indicator of oxidative stress. Twelve 6 month old Sprague Dawley rats were divided into two groups: 28 d of hindlimb unloading (n = 6) and controls (n = 6). Hindlimb unloading resulted in a small decrease in Mn-superoxide dismutase activity (10.1%) in the soleus muscle, while Cu,Zn-superoxide dismutase increased 71.2%. In contrast, catalase and glutathione peroxidase, antioxidant enzymes that remove hydroperoxides, were significantly reduced in the soleus with hindlimb unloading by 54.5 and 16.1%, respectively. Hindlimb unloading also significantly reduced ASC. Hindlimb unloading increased soleus lipid hydroperoxide levels by 21.6% and hindlimb muscle DCFH-DA oxidation by 162.1%. These results indicate that hindlimb unloading results in a disruption of antioxidant status, elevation of hydroperoxides, and an increase in oxidative stress.
 ...
PMID:Hindlimb unloading increases oxidative stress and disrupts antioxidant capacity in skeletal muscle. 1282 51

Aeromonas salmonicida subsp. salmonicida is a facultatively intracellular gram-negative bacterium that is the etiological agent of furunculosis, a bacterial septicemia of salmonids that causes significant economic loss to the salmon farming industry. The mechanisms by which A. salmonicida evades intracellular killing may be relevant in understanding virulence and the eventual design of appropriate treatment strategies for furunculosis. We have identified two open reading frames (ORFs) and related upstream sequences that code for two putative superoxide dismutases (SODs), sodA and sodB. The sodA gene encoded a protein of 204 amino acids with a molecular mass of approximately 23.0 kDa (SodA) that had high similarity to other prokaryotic Mn-SODs. The sodB gene encoded a protein of 194 amino acids with a molecular mass of approximately 22.3 kDa that had high similarity to other prokaryotic Fe-SODs. Two enzymes with activities consistent with both these ORFs were identified by inhibition of O(2)(-)-catalyzed tetrazolium salt reduction in both gels and microtiter plate assays. The two enzymes differed in their expression patterns in in vivo- and in vitro-cultured bacteria. The regulatory sequences upstream of putative sodA were consistent with these differences. We could not identify other SOD isozymes such as sodC either functionally or through data mining. Levels of SOD were significantly higher in virulent than in avirulent strains of A. salmonicida subsp. salmonicida strain A449 when cultured in vitro and in vivo.
 ...
PMID:Molecular characterization and quantitative analysis of superoxide dismutases in virulent and avirulent strains of Aeromonas salmonicida subsp. salmonicida. 1286 41

Although Haemophilus somnus causes septicemia and vasculitis in cattle, relatively little is known about how H. somnus affects endothelial cells in vitro. We previously reported that H. somnus lipooligosaccharide (LOS)-induced activation of caspases-3, -8 and -9, and apoptosis of bovine pulmonary artery endothelial cells (BPAEC) in vitro. Previous reports indicate that the generation of reactive oxygen species (ROS) or reactive nitrogen intermediates (RNI) can contribute to the induction of apoptosis. In the present study, we sought to determine whether ROS and RNI are involved in LOS-mediated apoptosis of BPAEC. We found that H. somnus LOS induced the generation of ROS in BPAEC, which was blocked by pretreatment with membrane permeable ROS scavengers, such as dimethylsulfoxide (DMSO) and allopurinol (AP). Addition of DMSO or AP significantly reduced H. somnus LOS-mediated caspase-3 activation. Addition of membrane impermeable ROS scavengers (e.g. catalase and superoxide dismutase), failed to block LOS-mediated caspase-3 activation, suggesting a role for intracellular generation of ROS in LOS-induced apoptosis of BPAEC. Addition of N(G)-nitro-L-arginine methyl ester (L-NAME) or aminoguanidine, which are selective inhibitors of nitric oxide synthase, blocked NO release and significantly reduced caspase-3 activation in LOS treated BPAEC. These data suggest H. somnus LOS triggers endogenous ROS and RNI production by endothelial cells, which contributes to apoptosis.
 ...
PMID:Reactive oxygen and nitrogen intermediates contribute to Haemophilus somnus lipooligosaccharide-mediated apoptosis of bovine endothelial cells. 1474 Nov 39

A new type adsorbent for removal of bacterial endotoxins was prepared by immobilizing lysine covalently onto cellulose beads. Endotoxins (Escherichia coli O55: B5) were injected into 13 healthy New Zealand white rabbits to induce infectious symptoms. Hemoperfusion using the adsorbent column removed endotoxins in the blood of eight rabbits during 2h while other five rabbits were used as control. The mean blood endotoxin concentration was reduced significantly from 5.56 +/- 0.54 EU/ml (1 EU = 100 pg) before treatment to 0.41 +/- 0.26 EU/ml after perfusion as measured by the limulus amebocyte lysate test (Chromogenix). Liver function and renal function tests showed significant improvement of septic symptoms in contrast to the control group. Other parameters such as superoxide dismutase and malondialdehyde were ameliorated markedly after the treatment. Moreover, the adsorbent showed good results in mechanical strength, blood compatibility and cytotoxicity, which suggested that lysine-cellulose adsorbent was of high ET-binding efficacy without significant side effect. It has a high potential of clinical application for treatment of patients with severe sepsis.
 ...
PMID:In vivo studies of endotoxin removal by lysine-cellulose adsorbents. 1513 Jul 28

The aim of this study was to investigate effects of sesame oil on oxidative stress after the onset of sepsis in rats. Effects of sesame oil on lipid peroxidation, superoxide anion, superoxide dismutase, catalase, glutathione, and nitrite after the onset of endotoxin intoxication were determined. To further examine the protective effect of sesame oil on sepsis, a mortality study was also conduced in cecal ligation and puncture-induced sepsis in rats. Sesame oil was given orally 6 h after endotoxin administration and cecal ligation and puncture, and parameters were then measured in another 6 h. Data demonstrated that a single dose of sesame oil reduced lipid peroxidation 6 h after endotoxin intoxication. Superoxide anion counts were decreased, glutathione levels were increased, and activities of superoxide dismutase and catalase, as well as nitrite levels, were not altered in lipopolysaccharide plus sesame oil-treated groups compared with lipopolysaccharide-treated groups. Furthermore, sesame oil given 6 h after cecal ligation and puncture significantly increased survival rate. Thus, we suggested that sesame oil could be used as a potent antioxidant to reduce oxidative stress after the onset of sepsis in rats.
 ...
PMID:Effects of sesame oil on oxidative stress after the onset of sepsis in rats. 1554 32

We studied the changes in superoxide dismutase activity in organs of Galleria mellonella larvae infected with two strains of Bacillus thuringiensis. A considerable increase in superoxide dismutase activity was observed at the initial stages of infection, later the enzyme activity decreased and this decrease was timed to cessation of feeding and development of sepsis in the infected larvae. Changes in the enzyme activity in the organs of larvae infected with a highly virulent strain of B. thuringiensis correlated with the stages of infection. Involvement of superoxide dismutase in prevention of oxidative stress in the infected larvae is discussed.
 ...
PMID:[Changes in superoxide dismutase activity in various larval organs of greater wax moth (Galleria mellonella L., Lepidoptera: Pyralidae) induced by infection with Bacillus thuringiensis ssp. galleriae]. 1576 35

We investigated the role of oxidative stress in the pathogenesis of septic ileus. Sepsis was induced by intraperitoneal (i.p.) injection of lipopolysaccharides (LPS, 20 mg kg(-1)) in mice. The effect of two i.p. injections of superoxide dismutase [polyethylene glycol (PEG)-SOD, 4000 U kg(-1)] and catalase (PEG-CAT, 15,000 U kg(-1)) was investigated on gastric emptying, intestinal transit and total nitrite plasma concentrations. We also performed immunohistochemical experiments on gastric and ileal tissue. LPS significantly delayed gastric emptying and intestinal transit while plasma nitrite levels increased. Polyethylene glycol (PEG)-SOD reversed the endotoxin-induced delay in gastric emptying and improved the delay in intestinal transit without effect on plasma nitrite levels. PEG-CAT slightly improved the delay in gastric emptying without effect on intestinal transit. Immunohistochemistry showed the presence of nitrotyrosine (NT) and 4-hydroxy-2-nonenal (HNE) in the gastric and ileal mucosa of LPS-treated mice. Treatment with PEG-SOD or PEG-CAT of LPS mice diminished the presence of NT or HNE in both tissues. In addition, LPS induced a significant increase in inducible nitric oxide synthase (iNOS)-positive residential macrophages in the external musculature of stomach and ileum, which significantly decreased after PEG-SOD or PEG-CAT treatment. The present results support a role for oxidative and nitrosative stress in the pathogenesis of septic ileus in mice.
 ...
PMID:Role of oxidative stress in the pathogenesis of septic ileus in mice. 1578 45

The antioxidant N-acetylcysteine (NAC) prevented sepsis-induced diaphragmatic dysfunction. As an indirect antioxidant NAC was shown to induce superoxide dismutase (SOD) activity in immune cells from endotoxaemic mice. The aim of this study was to assess whether NAC acts as an indirect antioxidant by inducing manganese (Mn)-SOD activity in the diaphragms of endotoxaemic rats, while preventing muscle dysfunction. A controlled study was conducted, in which protein carbonylation, Mn-SOD, catalase, and 3-nitrotyrosine immunoreactivity were detected using immunoblotting and immunohistochemistry in rat diaphragms. Six groups were studied for 24 h after a saline (control) or lipopolysaccharide (LPS; 20 mg.kg-1) i.p. injection in the absence and presence of NAC pre-treatment (either 1.5 or 3 mmol.kg(-1).24 h-1 for 7 days, oral administration). Diaphragm mitochondrial Mn-SOD activity and respiratory muscle function were also determined. Within 24 h, LPS induced maximal inspiratory pressure reduction, increasing diaphragmatic protein carbonylation and nitration. Pre-treatment with 3 mmol.kg-1 NAC clearly increased muscle Mn-SOD protein content and activity in both LPS- and saline-injected animals, while reducing protein carbonylation and nitration, and partially preventing the LPS-induced respiratory muscle dysfunction. Data produced from this study indicate that high doses of N-acetylcysteine induces manganese superoxide dismutase, as well as preserves its activity, possibly by preventing nitration of critical tyrosine residues of the enzyme.
 ...
PMID:N-acetylcysteine increases manganese superoxide dismutase activity in septic rat diaphragms. 1631 32

We investigated the importance of two enzymes (superoxide dismutase--SOD and glutathione peroxidase--GSH-Px) in the antioxidant defence of newborns and analysed their activity in: human colostrum and milk (from 63 mothers, after normal delivery, without complications or signs of infection), gastric fluid (from 10 breast-fed newborns, 7-28 days after birth; and from 15 artificially-fed newborns, with no signs of infection, 7-28 days after birth), and plasma (from 10 newborns, 1-28 days old, with no signs of infection, and 10 newborns, 1-28 days old, with signs of neonatal sepsis). The results of the study showed that there was statistically significant increased activity of SOD (p<0.001) in colostrum compared to mature milk. There was no statistically important difference in the activity of GSH-Px between those two samples. The activity of SOD in the gastric fluid of the artificially-fed newborns was statistically significantly lower than in the breast-fed newborns (p<0.001). The same results were found for mature mother's milk. We discovered a significant increase of SOD plasma activity in the newborns with sepsis, compared to the breast-fed newborns, with no signs of infection. The negative correlation between the activities of SOD and GSH-Px in the gastric fluid samples of the breast-fed and the artificially-fed newborns and the newborns with sepsis, showed that the activities of both enzymes were important for adequate antioxidant defence during the neonatal period. Breast-feeding with both colostrum and mature human milk is probably very important for adequate antioxidant defence in newborns.
 ...
PMID:[Importance of breast-feeding in antioxidant defence]. 1653 93


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>