Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0243026 (sepsis)
 52,417 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

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

Adult respiratory distress syndrome (ARDS) can develop as a complication of various disorders, including sepsis, but it has not been possible to identify which of the patients at risk will develop this serious disorder. We have investigated the ability of six markers, measured sequentially in blood, to predict development of ARDS in 26 patients with sepsis. At the initial diagnosis of sepsis (6-24 h before the development of ARDS), serum manganese superoxide dismutase concentration and catalase activity were higher in the 6 patients who subsequently developed ARDS than in 20 patients who did not develop ARDS. These changes in antioxidant enzymes predicted the development of ARDS in septic patients with the same sensitivity, specificity, and efficiency as simultaneous assessments of serum lactate dehydrogenase activity and factor VIII concentration. By contrast, serum glutathione peroxidase activity and alpha 1Pi-elastase complex concentration did not differ at the initial diagnosis of sepsis between patients who did and did not subsequently develop ARDS, and were not as effective in predicting the development of ARDS. Measurement of manganese superoxide dismutase and catalase, in addition to the other markers, should facilitate identification of patients at highest risk of ARDS and allow prospective treatment.
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PMID:Serum antioxidants as predictors of adult respiratory distress syndrome in patients with sepsis. 809 98

Because oxygen free radicals have been implicated in the endothelial cell damage and in the myocardial depression occurring during severe sepsis, we investigated whether N-acetyl-L-cysteine (NAC) could influence the oxygen extraction capabilities during an acute reduction in blood flow induced by cardiac tamponade after endotoxin challenge. Sixteen anesthetized, saline-infused, and ventilated dogs received Escherichia coli endotoxin (2 mg/kg) 30 min before tamponade was induced by repeated bolus injections of warm saline into the pericardial space. Thirty minutes before endotoxin administration, nine dogs received NAC (150 mg/kg, followed by a 20 mg.kg-1.h-1 infusion); the other seven dogs served as a control group. The NAC group maintained higher cardiac index, oxygen delivery (DO2), and left ventricular stroke work index, but lower systemic and pulmonary vascular resistance, than the control group. The oxygen uptake (VO2) levels at critical DO2 (DO2crit) were identical in the two groups. However, DO2crit was significantly lower in the NAC than in the control group (8.1 +/- 1.7 vs. 10.8 +/- 1.8 ml.kg-1.min-1, P < 0.01). Critical oxygen extraction ratio and the slope of the VO2-to-DO2-dependent line were higher in the NAC than in the control group (72 +/- 14 vs. 53 +/- 15% and 0.80 vs. 0.56, respectively; both P < 0.05). The peak lactate and the maximal tumor necrosis factor (TNF) levels were lower in the NAC than in the control group (5.2 +/- 0.4 vs. 7.6 +/- 0.4 mM, and 0.14 +/- 0.03 vs. 1.21 +/- 0.58 ng/ml, respectively; both P < 0.01). NAC significantly increased glutathione peroxidase activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Protective effects of N-acetyl-L-cysteine in endotoxemia. 820 75

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

Reactive oxygen species (ROS) are mediators of cellular injury and play a putative role in the onset of hepatic damage during endotoxemia or sepsis. It has been suggested that induction of glucose-6-phosphate (G-6-P) dehydrogenase, the key enzyme of the hexose monophosphate shunt (HMS), may support ROS-producing or ROS-eliminating pathways in hepatic endothelial and Kupffer cells during endotoxemia. The aim of the study was to assess in vivo lipopolysaccharide (LPS)-induced alterations in rat gene expression of selected enzymes that are in functional relationship with the HMS. mRNA levels and activities of glucose transporter GLUT-1, Mn- and CuZn-dependent superoxide dismutases (Mn-SOD and CuZn-SOD), and Se-dependent glutathione peroxidase (Se-GPX) were determined. Cellular extracts were analyzed 7 or 22 h after injection of LPS (Escherichia coli, 2 mg/kg ip) or injection of saline. Exposure to LPS for 7 or 22 h caused a 10- to 25-fold increase in GLUT-1 mRNA levels in endothelial and Kupffer cells. In parenchymal cells, GLUT-1 mRNA expression was low, and LPS caused no marked changes. Cellular levels of Mn-SOD mRNA were 20-40 times greater in all hepatic cells from LPS-treated animals than in cells from control rats. LPS at 22 h increased Mn-SOD activity by 45% in endothelial cells but caused no significant changes in Kupffer or parenchymal cells. Message levels and enzyme activities of CuZn-SOD and Se-GPX were significantly elevated 22 h after LPS injection in endothelial cells only. Thus LPS results in marked upregulation of functionally related genes in hepatic cells. In endothelial cells, the simultaneous upregulation of GLUT-1, G-6-P dehydrogenase, Mn-SOD, CuZn-SOD, and Se-GPX may represent an important mechanism for accelerated elimination of ROS released from activated sinusoidal phagocytes. In Kupffer cells, upregulated GLUT-1 and G-6-P dehydrogenase, together with constitutively present SOD and lack of upregulated Se-GPX, suggest an elevated capacity to produce O2- and H2O2 that is consistent with primed bacterial killing.
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PMID:Endotoxin stimulates gene expression of ROS-eliminating pathways in rat hepatic endothelial and Kupffer cells. 892 96

Selenium is an essential component of the intracellular antioxidant system as a structural component of the active center of the glutathione peroxidase enzymes. These selenoenzymes play a major role in protecting cells against peroxidation, especially lipid peroxidation and selenium seems to play a direct role in the regulation of inflammatory processes. In conditions of systemic inflammatory response or sepsis, patients are exposed to severe oxidative stress. These patients already have both, a decreased plasma selenium and glutathione peroxidase activity at admission to the ICU as has been shown in several studies. The degree of selenium deficiency is correlated with the severity of disease and the incidence of mortality. The reason for the low plasma selenium levels is unknown. Especially it would be of interest a) if the low plasma selenium is the consequence of the systemic inflammatory response with distribution of selenium in other compartments of the body, b) most important, whether the substitution of selenium might improve the outcome and decrease the mortality rate of these patients. In 2 independently performed intention-to-treat studies including patients with systemic inflammatory response syndrome or sepsis a beneficial effect of selenium supplementation on multiple organ function and outcome could already be demonstrated as well as a tendency of an improved mortality rate. A prospective analytical study clearly could demonstrate the inverse relationship between low plasma selenium and morbidity and mortality of patients with SIRS/sepsis. The results of these studies are so convincing, that we propose a randomized, prospective, double blind multicenter phase-III study including patients with systemic inflammatory response syndrome or sepsis to investigate, whether a high-dose selenium substitution in addition to the recommended treatment strategies for patients with sepsis improves outcome and mortality rate of these patients.
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PMID:[Significance of selenium in intensive care medicine. Clinical studies of patients with SIRS/sepsis syndrome]. 1055 31

Tumor necrosis factor-alpha (TNF-alpha) and free radicals have been implicated in the pathogenesis of neonatal septicemia and its complications. This case control study was conducted between November 1996 to July 1997 to determine the levels of TNF-alpha and free radical scavengers viz. superoxide dismutase (SOD) and glutathione peroxidase (GPX) in the serum of 30 septic neonates and 20 healthy controls. Patients with neonatal sepsis registered significantly higher levels of TNF-alpha, SOD and GPX in comparison to controls (p < 0.05). The neonates with septic shock had five fold increase in TNF-alpha levels (2262 +/- 605.8 pg/ml) as compared to those without shock (738.8 +/- 728.8 pg/ml). There was no statistically significant difference in levels of antioxidant enzymes between neonates with shock and without shock. The levels of TNF-alpha and antioxidant enzymes were not affected by the type of organism isolated in blood culture.
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PMID:Serum TNF-alpha and free radical scavengers in neonatal septicemia. 1079 4

Septicaemia is a major threat to survival during the early stages of life. There are several reports that suggest that reactive oxygen species (ROs) play a role in a wide variety of diseases. We estimated the activity of xanthine oxidase (XO), malondialdehyde (MDA) content, creatine phosphokinase (CPK) activity, activities of key enzymatic antioxidants, such as superoxide dismutase (SOD), glutathione peroxidase (GPx) and peroxidase (PO), and non-enzymatic antioxidants, viz. uric acid (UA) and albumin (ALB), in 30 neonates with sepsis and 20 age-matched controls. The babies were categorized as preterm/term, early onset/late onset, and shock/without shock, as per clinical and laboratory investigations. The study was carried out to evaluate the status of antioxidant enzymes and non-enzymatic antioxidants with a view to suggesting the introduction of antioxidant therapy in neonatal sepsis. The activities of serum XO, CPK, SOD and GPx, and the content of MDA were found to be significantly elevated in the neonates with sepsis when compared with controls. Conversely, the activity of PO and the levels of UA and ALB were decreased. The septic, full-term neonates registered significantly higher CPK activity (70%) than the preterm septic neonates. However, infants with late-onset and shock sepsis had a significant decrease in CPK activity (p < 0.05) compared with their corresponding sub-groups. Likewise, UA levels were found to be 28% depressed (p < 0.05) in the babies with late-onset sepsis and 51% increased (p < 0.001) in babies with shock compared with their respective sub-groups. Neonates with septic shock also registered a significant elevation in GPx activity (28%) compared with those without shock. This study suggests increased production of ROs in neonates with sepsis, as evidenced by the positive regulation of XO, SOD and GPx activity. The elevation of antioxidant enzymes, however, was not so effective as to protect from cellular damage and thereby result in higher MDA production. It is evident that antioxidant therapy might be useful in the management of neonates with sepsis but further detailed clinico-biochemical investigations are required to define effective antioxidant therapy.
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PMID:Alterations in antioxidant status during neonatal sepsis. 1082 10


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