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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study assessed the hepatic acute phase response and cellular Ca2+ regulation in septic animals and in hepatoma cell lines in vitro. Sepsis was induced in male Sprague-Dawley rats by implanting in their abdominal cavities fecal pellets impregnated with live Escherichia coli and Bacteroides fragilis. 8 h after implantations, rats were treated with diltiazem (1.2 mg/kg) or superoxide dismutase (SOD) (5 x 10(3) units/kg). After 24 h, plasma acute phase proteins (APP) were determined by immunoelectrophoresis, and hepatic APP-mRNAs by Northern blot hybridization. Effects of diltiazem, verapamil, or SOD on hepatic cells were determined in rat Reuber H-35 and human HepG2 hepatoma cells. Sepsis induced a significant increase in plasma APP and their hepatic mRNAs. Diltiazem and SOD reduced the sepsis-induced elevations in plasma lactate, the febrile response and mortality. APP expression in H-35 and HepG2 cells, stimulated by interleukin 1 (IL-1), IL-6, and dexamethasone, was inhibited by diltiazem or verapamil but not SOD. The results suggest that a heightened hepatic APP response in septic animals accompanies systemic/metabolic derangements and a significant animal mortality. Because diltiazem was previously shown to prevent sepsis-related disturbances in hepatic cellular Ca2+ regulation, its mediation of decrease in APP, systemic/metabolic response, and mortality may be effected through modifications in cellular Ca2+ regulation. The data from hepatoma cells show an attenuation of the AAP can result from direct effects of a calcium blocker. However, whether the blocker primarily modifies cellular Ca2+ regulation and secondarily effects APP gene expression, or directly effects gene expression remains unknown.
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PMID:Diltiazem and superoxide dismutase modulate hepatic acute phase response in gram-negative sepsis. 753 32

The prognostic potential of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) was evaluated in sepsis. Enzyme concentrations were determined in samples obtained from septic patients at time of diagnosis. Statistically significant increases in activities of total plasma SOD (P < 0.003, n = 32), erythrocyte (RBC) SOD (P < 0.007, n = 16), plasma CAT (P < 0.0001, n = 32), and RBC CAT (P < 0.005, n = 16) were found in septic patients when compared with healthy adult controls (n = 7). Further, within the group of septic patients, statistically significant differences were found for total plasma SOD (P < 0.05) and plasma CAT (P < 0.009) (but not for RBC determinations) when survivors (n = 15) were compared with nonsurvivors (n = 17). No significant differences were found for either plasma or RBC enzyme concentrations when patients who developed adult respiratory distress syndrome were compared with those who did not. The most striking finding was that plasma total SOD values of > 10 kU/L were found in 7 of 21 (30%) patients who did not survive their sepsis and that these values did not overlap with any surviving patients or controls. However, while high total plasma SOD activity appears to have some potential as a prognostic indicator, lower values (0.0-8.8 kU/L) do not. For plasma CAT, despite finding statistically significant differences between survivors and nonsurvivors, the substantial overlap in the values obtained for the two groups limits the practical prognostic potential of this enzyme.
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PMID:Prognostic role of antioxidant enzymes in sepsis: preliminary assessment. 776 6

Due to the chemical nature of oxygen, its tendency to accept a single electron to create the superoxide radical, and the fact that every aerobic cell must deal with this difficult situation, the production of oxygen-derived free radicals is an almost universal accompaniment to cellular pathology. In sepsis or immunologic disease, the activated phagocyte becomes a major producer of active oxygen species, contributing to oxidative injury to host tissues. The resulting oxidative stress is seriously exacerbated by the availability of iron, liberated from the body's store of ferritin. The antioxidant vitamins and the body's antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase) can help to restore and maintain proper oxidant/antioxidant balance.
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PMID:Oxygen-derived free radicals. 792 95

Sepsis, as infection associated to systemic manifestations, was produced in rats by cecal ligation and double perforation. Sham-operated rats were used as controls. The spontaneous chemiluminescence of rat adductor muscle and liver were measured at 6, 12, 24, and 30 h after the surgical procedure. Muscle chemiluminescence showed a maximal increase of about twofold (control emission 10 +/- 1 cps/cm2) after 6-12 h of sepsis, while liver chemiluminescence increased by about 80% (control emission: 11 +/- 1 cps/cm2) after 24 h of sepsis. The activities of muscle antioxidant enzymes were found maximally diminished after 12 h of sepsis: 46% decrease for Mn-superoxide dismutase, 83% decrease for catalase, and 55% decrease for glutathione peroxidase. In liver, only catalase activity showed a 52% decrease after 24 h of sepsis. State 3 oxygen uptake of muscle mitochondria with either malate-glutamate or succinate as substrates was 40% decreased after 12 h of sepsis in both cases. State 4 oxygen uptake of muscle mitochondria was not affected. The rate of H2O2 production of muscle mitochondria after 12 h of sepsis with either malate-glutamate or succinate as substrates was increased about 2.5 times but was not affected when assayed in the presence of as rotenone and antimycin. The oxygen uptake of liver mitochondria isolated from septic rats did not show differences as compared with those of control rats after 6 to 24 h of sepsis. Oxidative stress appears to occur in skeletal muscle early at the onset of the septic syndrome, with inhibition of active mitochondrial respiration and inactivation of antioxidant enzymes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Oxidative stress in muscle and liver of rats with septic syndrome. 800 29

Nitric oxide reacts with superoxide to form peroxynitrite, a potential mediator of oxidant-induced cellular injury. The endothelium is a primary target of injury in many pathological states, including acute lung injury, sepsis, multiple organ failure syndrome, and atherosclerosis, where enhanced production of nitric oxide and superoxide occurs simultaneously. It was hypothesized that stimulation of endothelial cell nitric oxide production would result in formation of peroxynitrite. Immediate oxidant production was detected by luminol- and lucigenin-enhanced chemiluminescence from cultured bovine aortic endothelial cells exposed to bradykinin or to the calcium ionophore A23187. Luminol-enhanced chemiluminescence was efficiently inhibited by the nitric oxide synthase inhibitor nitro-L-arginine methyl ester and by superoxide dismutase, implying dependence on the presence of both nitric oxide and superoxide for oxidant production. Inhibition of luminol-enhanced chemiluminescence by nitro-L-arginine methyl ester was partially reversed by L-arginine, but not by D-arginine. Cysteine, methionine, and urate, known inhibitors of peroxynitrite-mediated oxidation, inhibited luminol-enhanced chemiluminescence, while the hydroxyl radical scavengers, mannitol and dimethylsulfoxide, and catalase did not. Bicarbonate increased luminol-enhanced chemiluminescence in a concentration-dependent manner. Superoxide production, detected by lucigenin-enhanced chemiluminescence, was slightly increased in the presence of nitro-L-arginine methyl ester, suggesting that endothelial cell-produced superoxide was partially metabolized by reaction with nitric oxide. These results are consistent with agonist-induced peroxynitrite production by endothelial cells and suggests that peroxynitrite may have an important role in oxidant-induced endothelial injury.
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PMID:Agonist-induced peroxynitrite production from endothelial cells. 817 19

Distinct alterations in fatty acid composition and in the functional state of erythrocyte membranes were detected in 58 patients with sepsis; these alterations were phase-dependent and correlated highly with clinical picture. Considerable increase in content of saturated and monounsaturated fatty acids and a decrease in concentration of lipoproteins were found in erythrocyte membranes under inauspicious conditions of sepsis development. In these patients activities of superoxide dismutase and glucose-6-phosphate dehydrogenase were decreased, while content of SH-groups was lowered and lipid peroxidation was inhibited. The alterations observed in fatty acid composition of erythrocyte membranes and a decrease in metabolic activity of red blood cells may be responsible for hemolysis in patients with sepsis.
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PMID:[Fatty acid composition and functional status of erythrocyte membranes in patients with sepsis]. 827 33

Skeletal muscle is a target organ during sepsis; nevertheless, there is no evidence of a possible free radical overproduction with tissue damage in this situation. We studied Sprague Dawley female rats in two groups: a septic group with cecal ligation and double cecal perforation and a control group that was sham operated. Hind limb adductor muscles spontaneous chemiluminescence was measured at 2, 4, 6, 12, 24, and 30 hr after the surgical procedure as the expression of oxygen excited species generation. Muscle samples were also taken and activity of the principal antioxidant enzymes--superoxide dismutase (SOD), catalase, and glutathione peroxidase--as well as myeloperoxidase, an index of neutrophil infiltration was determined. CPK seric assays at 12 and 24 hr were used to reflect muscle injury and revealed high levels. Previously administered bovine superoxide dismutase was employed to prevent or attenuate oxidative stress. The results showed that light emission by rat skeletal muscle doubled from 4 to 12 hr of sepsis and could be attenuated with SOD pretreatment. Observed changes may be attributed to the production of oxygen free radicals that do not depend on local neutrophil infiltration. The detoxifying antioxidant enzyme activities in skeletal muscle were diminished (Mn SOD 46% at 6 hr, catalase 83% at 12 hr glutathione peroxidase 55% at 12 hr), which would also facilitate muscle septic damage.
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PMID:Oxidative stress in skeletal muscle during sepsis in rats. 838 98

In gram-negative septicemia, endotoxin-induced free radicals probably damage the liver cells by membrane lipid peroxidation. Phosphotidylcholine hydroperoxide (PCOOH), a primary lipid peroxidation product can be applied as a parameter to measure the extent of liver damage. The protective effects of urinastatin and free radical scavengers, superoxide dismutase (SOD), and catalase against hepatic lipid peroxidation and tissue energy reserves in the liver during endotoxemia were evaluated in rats with gram-negative septicemia induced by cecal ligation and puncture (CLP). One hundred and sixty-five rats were divided into three groups. The first two groups consisted of 45 rats each. Group (1) was used for blood endotoxin level and liver function tests, group (2) for hepatic energy charge and PCOOH measurement, and group (3) (n = 75) for survival study. In each group, control animals received saline injection only. Urinastatin was injected twice intravenously through tail veins using 50,000 u/kg at 0 and 12 hr after CLP. SOD 90,000 u/kg and catalase 50,000 u/kg were given subcutaneously just before CLP and every 3 hr thereafter up to 24 hr. Liver and blood specimens were taken at time points 0, 12, and 24 hr after CLP. Increased concentration of PCOOH in liver denotes that endotoxemia can damage the liver by hepatocellular lipid peroxidation. Attenuation of lipid peroxidation, which correlated with liver enzyme leakage, was noted by finding significant decreased concentrations of PCOOH (P < 0.001), improvement in energy charge (P < 0.05), and survivability (P < 0.05) was seen in urinastatin or radical scavenger-treated groups. These results suggested that urinastatin has protective effect against free radical-induced lipid peroxidation probably by inhibiting proteases especially elastase, from polymorphonuclear leucocytes. SOD and catalase, which scavenged oxygen free radicals, also suppressed free radical-induced lipid peroxidation. Improvement in survivability was also seen in treated groups.
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PMID:Effects of urinastatin and free radical scavengers on hepatic lipid peroxidation in endotoxemia. 876 68

Nitric oxide release is induced in many cells, including vascular endothelium, as part of the host response to inflammation. Nitric oxide synthase activity is increased in patients with sepsis, associated with increased oxidant demands and decreased antioxidant protection. We used a human vascular endothelial cell line to investigate the influence of antioxidants on nitric oxide synthase activity. Cells were cultured to confluence and incubated with interferon gamma, tumor necrosis factor, and lipopolysaccharide in the combined presence of the antioxidants ascorbic acid, Trolox, catalase, or superoxide dismutase, singly and in combination, for 48 h. Additionally, some cells were incubated with hypoxanthine-xanthine oxidase or a nitric oxide donor. Nitric oxide synthase activity was upregulated by cytokine exposure (p < .0005). Ascorbic acid and superoxide dismutase/ catalase resulted in decreased enzyme activity (p < .05). Superoxide anion release from xanthine oxidase caused increased activity (p < .05) and exogenous nitric oxide tended to suppress synthase activity. We suggest that antioxidants scavenge superoxide anion, enabling feedback inhibition of nitric oxide synthase activity by nitric oxide, and thus reducing enzyme activity. Exogenous nitric oxide also has a similar effect. Superoxide generation suppresses this feedback inhibition. This study has important implications in patients with sepsis in whom nitric oxide synthase inhibitor therapy is currently under investigation.
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PMID:Regulation of nitric oxide synthase activity in cultured human endothelial cells: effect of antioxidants. 879 Oct 97

Reactive oxygen metabolites (ROMs) are thought to play a key role in the pathogenesis of the adult respiratory distress syndrome (ARDS). Accordingly, the use of ROM scavengers, such as N-acetyl-cysteine or dimethylthiourea, as therapeutic adjuncts to prevent oxidant-mediated damage to the lung have been evaluated extensively in animal models of ARDS. Results with this approach have been quite variable among studies. Another strategy that has been examined in animal models of ARDS is the administration of various enzymes, particularly superoxide dismutase (SOD) or catalase (CAT), in an effort to promote the conversion of ROMs to inactive metabolites. In theory, this strategy should be more effective than the use of ROM scavengers since a single molecule of a catalytically active molecule can neutralize a large number of molecules of a reactive species, whereas most scavengers act in a stoichiometric fashion to neutralize radicals on a mole-for-mole basis. This notion is supported by studies showing that prophylactic treatment with CAT provides impressive protection against acute lung injury induced in experimental animals by the administration of lipopolysaccharide (LPS). Results with SOD have been more variable. Recently, we have utilized a porcine model of LPS-induced ARDS to investigate the therapeutic potential of EUK-8, a novel, synthetic, low molecular salen-manganese complex that exhibits both SOD-like and CAT-like activities in vitro. Using both pre- and post-treatment designs, we have documented that treatment with EUK-8 significantly attenuates many of the features of LPS-induced acute lung injury, including arterial hypoxemia, pulmonary hypertension, decreased dynamic pulmonary compliance, and pulmonary edema. These findings support the view that salen-manganese complexes warrant further evaluation as therapeutic agents for treatment or prevention of sepsis-related ARDS in humans.
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PMID:Role of oxidant stress in the adult respiratory distress syndrome: evaluation of a novel antioxidant strategy in a porcine model of endotoxin-induced acute lung injury. 882 94


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