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)

Excessive hydrogen peroxide (H2O2) generation appears to contribute to the development of the adult respiratory distress syndrome (ARDS), but H2O2-combatting antioxidant defenses have not been evaluated. We found that serum from septic patients with ARDS scavenged more (p less than 0.05) H2O2 in vitro (82.7 +/- 3.8%) than did serum from septic patients without ARDS (56.9 +/- 3.1%) or control subjects (20.2 +/- 2.4%). Serum from septic patients with ARDS also had more (p less than 0.05) catalase activity (54.9 +/- 10.9 U/ml) than did serum from septic patients without ARDS (28.6 +/- 3.4 U/ml) or control subjects (7.3 +/- 0.8 U/ml). In contrast, serum from septic patients with or without ARDS and control subjects had the same glutathione peroxidase (GPX) activity. Serum H2O2 scavenging activity correlated with serum catalase (r = 0.77) but not GPX (r = 0.33) activity and was inhibitable (greater than 90%) by sodium azide, a catalase inhibitor. Increases in serum catalase activity did not appear to be derived from erythrocytes (RBC) because septic patients with or without ARDS and control subjects had similar RBC hemolysis in response to osmotic stress in vitro and serum haptoglobin concentrations. Serum from septic patients with ARDS also protected endothelial cells against H2O2-mediated damage (34.5 +/- 2.2% 51Cr release) better (p less than 0.05) than serum from septic patients without ARDS (47.3 +/- 7.4%) or control subjects (82.1 +/- 10.2%), but killing of bacteria by neutrophils in vitro was the same in serum from patients and control subjects. Our findings indicate that patients with sepsis and/or ARDS have increased serum catalase activity, which may alter H2O2-dependent processes.
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PMID:Increased serum catalase activity in septic patients with the adult respiratory distress syndrome. 141 29

We examined the effects of tumor necrosis factor-alpha (TNF alpha) stimulation of endothelial cells on the increase in endothelial permeability induced by H2O2. Bovine pulmonary microvascular endothelial cells (BPMVEC) were grown to confluence on a microporous filter and the 125I-albumin clearance rate across the monolayer was determined. Pretreatment with TNF alpha (100 U/ml) for 6 h had no direct effect on transendothelial 125I-albumin permeability. However, TNF alpha pretreatment enhanced the susceptibility of BPMVEC to H2O2; that is, H2O2 (10 microM) alone had no direct effect, whereas H2O2 increased 125I-albumin permeability more than threefold when added to monolayers pretreated for 6 h with TNF alpha. Determination of lactate dehydrogenase release indicated that increased permeability was not due to cytolysis. We measured the intracellular contents of GSH and catalase to determine their possible role in mediating the increased susceptibility to H2O2. TNF alpha treatment (100 U/ml for 6 h) decreased total GSH content and concomitantly increased the oxidized GSH content, but did not alter the cellular catalase activity. The role of GSH was examined by pretreating endothelial cells with 2 mM GSH for 3 h, which produced an 80% increase in intracellular GSH content. GSH repletion inhibited the increased sensitivity of the TNF alpha-treated endothelial cells to H2O2. We tested the effects of xanthine oxidase (XO) inhibition since XO activation may be a source of oxidants responsible for the decrease in cellular GSH content. Pretreatment with 0.5 mM oxypurinol attenuated the synergistic effect of TNF alpha and H2O2 on endothelial permeability. The results indicate that decreased oxidant buffering capacity secondary to TNF alpha-induced reduction in intracellular GSH content mediates the increased susceptibility of endothelial cells to H2O2. This mechanism may contribute to oxidant-dependent vascular endothelial injury in septicemia associated with TNF alpha release.
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PMID:Tumor necrosis factor-alpha-mediated decrease in glutathione increases the sensitivity of pulmonary vascular endothelial cells to H2O2. 154 73

We investigated the effects of untreated intraabdominal sepsis on the interrelationship between PMN oxidative metabolism and cell surface receptor expression. Female swine underwent either sham laparotomy (n = 7) or cecal ligation and incision (n = 9) with assays conducted on postoperative days (POD) 0, 1, 4, and 8. Superoxide anion production, intracellular H2O2 production, and the cell surface expression of Fc gamma RII, III, CR1, and CR3 were measured. In addition, phagocytosis of serum-opsonized zymosan was used as a multivalent ligand for CR3 and subsequently Fc gamma RII, III, and CR1 expression were assayed to determine if intraabdominal sepsis induces a linkage between complement and Fc gamma receptor expression. Superoxide anion production increased between POD 0 and 4 and fell between POD 4 and 8 in animals with untreated intraabdominal sepsis. Intracellular H2O2 production rose between POD 0 and 1 and then fell progressively in animals with untreated intraabdominal sepsis. Simulation of the oxidative burst using glucose/glucose oxidase reduced Fc gamma RII and III expression in both sets of animals with a greater reduction seen by POD 4 in animals with intraabdominal sepsis. CR1/CR3 expression was increased with glucose/glucose oxidase by POD 4 in the presence of intraabdominal sepsis. Xanthine/xanthine oxidase did not alter cell surface receptor expression. Phagocytosis of serum-opsonized zymosan decreased subsequent Fc gamma RII expression in animals with intraabdominal sepsis by POD 4.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intraabdominal sepsis: enhanced autooxidative effect on polymorphonuclear leukocyte cell surface receptor expression. 166 27

The haem enzyme myeloperoxidase (MPO) (EC 1.11.1.7) with a spectral A430/A280 ratio greater than 0.7 and a specific activity of 125 U/mg was purified from isolated human neutrophils. To obtain a radioimmunoassay (RIA) for this enzyme, a specific antiserum against human neutrophil MPO was raised in rabbits and used at an initial dilution of 1/10,000. MPO labelled with 125iodine by a technique of self-labelling in the presence of H2O2, had a specific activity of 24 mCi/mg. After incubation at room temperature (2 h) and separation by double antibody precipitation in the presence of polyethylene glycol, the sensitivity of the RIA was 21 ng/ml. The RIA showed good precision and accuracy with intra- and interassay coefficients of variation of less than 7% for MPO concentrations ranging from 100 to 800 ng/ml, and satisfactory recoveries of known amounts of exogenous MPO in plasma. For the measurement of MPO in blood, the best sampling technique was to collect blood into EDTA. Rapid centrifugation (within 20 min) was necessary for blood collected into heparin. Mean MPO values in normal individuals were 340 +/- 98 ng/ml in EDTA plasma (n = 152) and 332 +/- 82 ng/ml in heparinized plasma (n = 34). When MPO was measured 12-6 h after injury in critically ill patients high values (above 1000 ng/ml) were found in 6/15 patients with multiple injuries. In patients with sepsis (n = 22), MPO values were always above 1000 ng/ml.
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PMID:Fast double antibody radioimmunoassay of human granulocyte myeloperoxidase and its application to plasma. 184 40

Activated polymorphonuclear neutrophils (PMN) and neutrophil activating mediators such as tumor necrosis factor-alpha (TNF-alpha) are thought to be involved in the pathophysiology of sepsis and multiple organ failure syndrome (MOFS). In critically ill patients at high risk for the development of septic syndrome (n = 17) peripheral blood PMN were assayed for O2- and H2O2 production after stimulation with phorbol myristate acetate (PMA, 40 nM). Serum TNF-alpha levels were determined by ELISA. At the time of admission to the intensive care unit we found significant higher levels of TNF-alpha (P = 0.0001) in the serum of patients finally developing sepsis correlating to higher respiratory burst capability in comparison to nonseptic patients. Additionally we were able to demonstrate a significant (P = 0.0016) lower dismutation rate of O2- to H2O2 in deceased patients in comparison to survivors. These results give further evidence that elevated levels of circulating TNF-alpha and activated PMN play a significant role in the pathogenesis of septic syndrome in critically ill patients.
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PMID:Respiratory burst capability of polymorphonuclear neutrophils and TNF-alpha serum levels in relationship to the development of septic syndrome in critically ill patients. 184 53

Neutrophil (PMN) functions, such as production of toxic oxygen (O2) metabolites, adherence, and chemotactic properties, are modified during local tissue inflammation and sepsis. We hypothesized that PMN would be primed during their transit through injured tissue beds, which in turn can lead to modulation or retention of the primed PMN by downstream tissues like the lungs. We tested this hypothesis by measuring the transpulmonary gradient of hydrogen peroxide (H2O2) production by zymosan-activated PMN. We examined the mixed venous to arterial difference in H2O2(delta H2O2) produced by zymosan-activated PMN in septic patients without lung infiltrates, patients with lung injury, and a control group of patients undergoing elective surgery or coronary catheterization. Septic patients had higher mixed venous H2O2/10(6) PMN, whereas lung injury patients had higher arterial H2O2/10(6) PMN. The control group had the same H2O2/10(6) PMN in mixed venous and arterial blood. The delta H2O2 in septic, lung injury, and control groups were 0.35 +/- 0.22, -0.31 +/- 0.48, and -0.01 +/- 0.04 nmol H2O2/10(6) PMN, respectively. The mixed venous to arterial H2O2 gradient distinguished septic patients from the control and lung injury patients (p less than 0.05). Our results are consistent with the hypothesis that in septic patients PMN are primed in the periphery and downregulated or sequestered in the lung, and in lung injury patients PMN are primed in the lung and sequestered in the periphery. Alternatively, neutrophil-endothelial interactions may downregulate toxic O2 metabolite production by PMN during their transit through microvascular beds.
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PMID:Differential activation of mixed venous and arterial neutrophils in patients with sepsis syndrome and acute lung injury. 202 18

The myeloperoxidase-hydrogen peroxide-chloride (MPO-H2O2-Cl) system is an antimicrobial system of polymorphonuclear leukocytes. We demonstrated that the MPO-H2O2-Cl system is fungicidal for Trichophyton rubrum. Fungal growth of a synchronous cell culture of T. rubrum germlings was assayed by measuring the uptake of tritiated N-acetyl-D-glucosamine, and the viability of the fungi was assayed by counting colony-forming units. Cytotoxins produced by the interaction of myeloperoxidase with hydrogen peroxide and chloride ion were fungicidal for T. rubrum. Growth inhibition was abolished in the presence of catalase or L-methionine. Polymorphonuclear leukocytes through the MPO-H2O2-Cl system may prevent invasion and sepsis by dermatophytes even in the absence of specific immunity.
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PMID:Inhibition of growth of Trichophyton rubrum by the myeloperoxidase-hydrogen peroxide-chloride system. 253 15

The ability of polymorphonuclear leukocytes to kill bacteria and yeast is reflected by cellular chemiluminescence or similarly by the production of H2O2 during oxidative metabolism. With the use of flow cytometry and 2'7' dichlorodihydrofluorescein-diacetate, we determined the direct effect of thermal injury and the indirect effect of burn serum on murine polymorphonuclear leukocyte oxidative metabolism after stimulation on days 1, 5, and 10 after 25% total body surface area burn. Control or burn peritoneal leukocytes and 10% control or burn serum were incubated in vitro with 2'7' dichlorodihydrofluorescein-diacetate for 15 minutes, then stimulated with phorbol 12-myristate 13-acetate. The change in polymorphonuclear leukocyte fluorescence was calculated from fluorescence histograms before and after stimulation. The oxidative metabolism of burn polymorphonuclear leukocytes was clearly depressed on days 5 and 10 after burn injury. Control polymorphonuclear leukocytes in the presence of day 5 burn serum produced decreased levels of H2O2, returning to normal by day 10. In general, bactericidal activity is markedly depressed on days 5 and 10 after thermal injury and may be associated with increased risk of sepsis.
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PMID:The effect of thermal injury on murine neutrophil oxidative metabolism. 270 18

Acute hypoxemic respiratory failure (AHRF) can result from diverse lung insults. Toxic oxygen metabolites have been implicated in this clinical condition and in animal models of pulmonary edema. Hydrogen peroxide (H2O2), an oxygen metabolite, mediates tissue injury. We measured H2O2 levels by a spectrophotometric technique in the breath condensate of 68 mechanically ventilated patients; 13 patients with normal lungs undergoing elective surgery had no such detectable levels of H2O2. Fifty-five patients in the ICU meeting criteria for the adult respiratory distress syndrome (ARDS) had a higher concentration of H2O2 in the expired breath condensate than ICU patients without pulmonary infiltrates (2.34 +/- 1.15 vs 0.99 +/- 0.72 mumol/L, p less than 0.005). This marker had a sensitivity of 87.5 percent and a specificity of 81.3 percent in separating the two patient populations. Patients with AHRF and focal pulmonary infiltrates who did not meet criteria for ARDS also had higher concentrations of H2O2 (2.45 +/- 1.55 mumol/L) than patients without pulmonary infiltrates (p less than 0.001). No difference was observed between the expired H2O2 concentrations of patients with ARDS or patients with focal pulmonary infiltrates. Patients with brain injury or sepsis tended to have higher levels of H2O2 regardless of lung pathology. Increased levels of H2O2 are detected in the expired breath of ICU patients with focal lung infiltrates and in ARDS patients, which is consistent with the hypothesis that oxygen metabolites participate in the pathogenesis of ARDS and other forms of AHRF.
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PMID:Increased hydrogen peroxide in the expired breath of patients with acute hypoxemic respiratory failure. 276 20

Eighteen white rabbits were subjected to a 30 per cent TBSA full thickness burn. Wound infection was found 9-13 days after injury and became severe a week or so later. ATPase activities, antioxidation ability, the proteins of erythrocyte membranes, and the Na+ contents of erythrocytes and serum were determined. The Ca++-ATPase activity was elevated during the first 17 days postburn, but showed a decline at the time of severe wound infection; the Na+,K+-ATPase activity showed peaks on postburn days 2 and 6, and then fluctuated above the preburn level. The change in Mg++-ATPase activity was similar to Na+,K+-ATPase. The erythrocyte Na+ content was increased, and the level of serum Na+ was decreased up to postburn day 6. Subsequently the erythrocyte Na+ was reduced and the serum Na+ increased up to day 17 postburn. The percentage of erythrocyte haemolysis in H2O2 was increased after the burn and became markedly so during wound infection, indicating that the antioxidation ability of burned rabbit erythrocytes was markedly impaired. During the period of wound infection, Coomassie blue-stained protein bands in SDS-polyacrylamide gel showed some changes in size and proportion in burned rabbits. For example, the second band was wider, the band 2 to band 1 ratio increased, and band 5 was smaller than before injury. These results seem to show that burn injury, especially when associated with sepsis, may affect both the structure and function of biological membranes.
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PMID:Changes in erythrocyte membranes in burned rabbits. 285 50


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