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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this review-hypothesis is to discuss the literature which had proposed the concept that the mechanisms by which infectious and inflammatory processes induce cell and tissue injury, in vivo, might paradoxically involve a deleterious synergistic 'cross-talk', among microbial- and host-derived pro-inflammatory agonists. This argument is based on studies of the mechanisms of tissue damage caused by catalase-negative group A hemolytic streptococci and also on a large body of evidence describing synergistic interactions among a multiplicity of agonists leading to cell and tissue damage in inflammatory and infectious processes. A very rapid cell damage (necrosis), accompanied by the release of large amounts of arachidonic acid and metabolites, could be induced when subtoxic amounts of oxidants (superoxide, oxidants generated by xanthine-xanthine oxidase, HOCl, NO), synergized with subtoxic amounts of a large series of membrane-perforating agents (streptococcal and other bacterial-derived hemolysins, phospholipases A2 and C, lysophosphatides, cationic proteins, fatty acids, xenobiotics, the attack complex of complement and certain cytokines). Subtoxic amounts of proteinases (elastase, cathepsin G, plasmin, trypsin) very dramatically further enhanced cell damage induced by combinations between oxidants and the membrane perforators. Thus, irrespective of the source of agonists, whether derived from microorganisms or from the hosts, a triad comprised of an oxidant, a membrane perforator, and a proteinase constitutes a potent cytolytic cocktail the activity of which may be further enhanced by certain cytokines. The role played by non-biodegradable microbial cell wall components (lipopolysaccharide, lipoteichoic acid, peptidoglycan) released following polycation- and antibiotic-induced bacteriolysis in the activation of macrophages to release oxidants, cytolytic cytokines and NO is also discussed in relation to the pathophysiology of granulomatous inflammation and sepsis. The recent failures to prevent septic shock by the administration of only single antagonists is disconcerting. It suggests, however, that since tissue damage in post-infectious syndromes is caused by synergistic interactions among a multiplicity of agents, only cocktails of appropriate antagonists, if administered at the early phase of infection and to patients at high risk, might prevent the development of post-infectious syndromes.
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PMID:Can we learn from the pathogenetic strategies of group A hemolytic streptococci how tissues are injured and organs fail in post-infectious and inflammatory sequelae? 1049 63

Organisms with little pathogenic potential in immunocompetent hosts may produce disease in HIV-1 + patients. We describe three HIV-1 + patients in late disease who presented with pruritic papules with central ulceration over the face and arms. In all the patients the eruptions had been present for months, and the patients did not develop sepsis. Biopsy specimens in all the patients showed large Gram-positive cocci, forming tetrads. Colony morphology, catalase positivity and coagulase negativity, and resistance to nitrofurantoin were used to separate micrococci from staphylococci. Micrococcus species are usually considered normal inhabitants of the skin; however, in patients with HIV-1 disease, Micrococcus species can produce localized cutaneous infections.
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PMID:Micrococcus folliculitis in HIV-1 disease. 1058 69

A 4-day-old baby weighing 1.7 kg was admitted to the neonatal intensive care unit of Ga-Rankuwa Hospital, Pretoria, with a history of apneic attacks. On examination there was an umbilical sepsis and the neonate was septicemic. The baby had been delivered at home and the umbilical cord had been cut by the grandmother using unclean scissors and chimney soot applied to the umbilical stump. On admission, a septic screen was done and antibiotic treatment was started with penicillin and amikacin. The investigations showed that the baby was slightly anemic, with hemoglobin levels of 10.0 g/dL (14.9-23.7 g/dL), and a pure growth of a Gram-negative bacillus was obtained from the cerebrospinal fluid, blood culture and suprapubic aspirate urine specimens. The Gram-negative bacillus was catalase and oxidase positive and it was identified as Pasteurella gallinarum. Antimicrobial profiling showed the organism to be susceptible to penicillin, cefotaxime, gentamicin and amikacin. Despite having received antimicrobial agents to which the etiological agent was susceptible, the neonate died within 5 days of admission. The cause of death was postulated to be due to overwhelming sepsis which resulted in septic shock.
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PMID:Pasteurella gallinarum neonatal meningitis. 1266 60

Nitric oxide (*NO) and its by-products modulate many physiological functions of skeletal muscle including blood flow, metabolism, glucose uptake, and contractile function. However, growing evidence suggests that an overproduction of nitric oxide contributes to muscle wasting in a number of pathologies including chronic heart failure, sepsis, COPD, muscular dystrophy, and extreme disuse. Limited data point to the potential of inhibition various enzymes by reactive nitrogen species (RNS), including (.)NO and its downstream products such as peroxynitrite, primarily in purified systems. We hypothesized that exposure of skeletal muscle to RNS donors would reduce or downregulate activities of the crucial antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX). Diaphragm muscle fiber bundles were extracted from 4-month-old Fischer-344 rats and, in a series of experiments, exposed to either (a) 0 (control), 1, or 5 mM diethylamine NONOate (DEANO: *NO donor); (b) 0, 100, 500 microM, or 1 mM sodium nitroprusside (SNP: *NO donor); (c) 0 or 2 mM S-nitroso-acetylpenicillamine (SNAP: *NO donor); or (d) 0 or 500 microM SIN-1 (peroxynitrite donor) for 60 min. DEANO resulted in a 50% reduction in CAT, GPX, and a dose-dependent inhibition of Cu, Zn-SOD. SNP resulted in significantly lower activities for total SOD, Mn-SOD isoform, Cu, Zn-SOD isoform, CAT, and GPX in a dose-dependent fashion. Two millimolar SNAP and 500 microM SIN-1 also resulted in a large and significant inhibition of total SOD and CAT. These data indicate that reactive nitrogen species impair antioxidant enzyme function in an RNS donor-specific and dose-dependent manner and are consistent with the hypothesis that excess RNS production contributes to skeletal muscle oxidative stress and muscle dysfunction.
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PMID:Specificity of antioxidant enzyme inhibition in skeletal muscle to reactive nitrogen species donors. 1207 89

Shock states induce the expression of inducible nitric oxide synthase (iNOS) in both Kupffer cells and hepatocytes in the liver, but little is known about its subcellular localization in these cells. Studies were undertaken to characterize the subcellular location of iNOS in hepatocytes in response to sepsis. By immunofluorescence analysis, intraperitoneal challenge with bacterial lipopolysaccharide induced cytosolic iNOS in Kupffer cells but punctate labeling in hepatocytes. Cultured rat hepatocytes exposed to interferon gamma, interleukin 1, and tumor necrosis factor alpha showed iNOS protein expression within peroxisomes as early as 4 hours after stimulation, as determined by colabeling for catalase or PMP70. To a lesser extent, iNOS was also observed associated with the plasma membrane and in undefined intracellular aggregates. The nitric oxide synthase (NOS) antagonist L-N-imino-ornithine (L-NIO) did not affect the expression of iNOS within peroxisomes, cytoplasmic aggregates, or cytosol but increased plasma membrane localization of iNOS. Human iNOS transduced into iNOS-null mouse hepatocytes using an adenoviral vector also localized to peroxisomes. The expression of iNOS often resulted in the disappearance of detectable catalase in many hepatocytes. In conclusion, these studies establish the peroxisome as a site of iNOS localization in hepatocytes and show a relationship between iNOS up-regulation and decreased expression of catalase.
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PMID:Peroxisomal localization of inducible nitric oxide synthase in hepatocytes. 1208 52

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.
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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.
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PMID:Hindlimb unloading increases oxidative stress and disrupts antioxidant capacity in skeletal muscle. 1282 51

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.
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PMID:Effects of sesame oil on oxidative stress after the onset of sepsis in rats. 1554 32

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.
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PMID:Role of oxidative stress in the pathogenesis of septic ileus in mice. 1578 45

Several studies demonstrated that previous heat shock treatment caused expression of heat shock proteins (HSPs) and reduced organ dysfunction and mortality in experimentally induced severe sepsis. However, the protective mechanism on platelet function remains unclear. The aim of this study was to investigate the effect of heat shock treatment on platelet aggregation ex vivo in endotoxin-induced rats with sepsis. Rats of the heated group were heated by whole-body hyperthermia 18 h before lipopolysaccharide (LPS) injection. Blood samples were obtained from the carotid artery 90 min after LPS injection. Platelet aggregation ability was measured by aggregometer. Results revealed that platelet aggregation ex vivo was significantly inhibited in LPS-induced rats in a manner of dose dependence. Previous heat shock treatment caused overexpression of HSPs and significantly attenuated the LPS-induced platelet hyporesponsiveness. This attenuation disappeared in accordance with absence of HSP72 at 7 days after heat shock treatment. Aggregation of normal platelets was also inhibited by incubating with plasma obtained from endotoxemic rats but not from preheated endotoxemic rats. Furthermore, no significant hyporesponsiveness was found in endotoxemic platelets in addition to preheated endotoxemic plasma. The addition of H2O2 scavenger catalase diminished the platelet hyporesponsiveness significantly only in nonheated endotoxemic rats. Moreover, the plasma nitrite and nitrate levels were significantly attenuated in preheated endotoxemic rats. These results revealed that previous heat shock treatment might attenuate LPS-induced hyporesponsiveness of platelets by changing the plasma components possibly through altering H2O2 and nitric oxide concentrations.
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PMID:Previous heat shock treatment attenuates lipopolysaccharide-induced hyporesponsiveness of platelets in rats. 1613 63


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