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)

A case of Brucella melitensis septicemia in a second-trimester pregnancy causing intrauterine fetal death and Gram-negative septic shock with diffuse intravascular coagulation is reported. The literature is reviewed. This is the first reported case of human brucellosis in association with Gram-negative sepsis and DIC during pregnancy. The importance of blood cultures and agglutinins for Brucella in febrile pregnant patients is re-emphasized.
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PMID:Brucella septicemia in pregnancy. 718 63

A review of the cases of 144 women who presented to the University of Ilorin (Nigeria) Teaching Hospital between July 1992 and June 1994 with complications of illegal abortion underscores the health hazards associated with this procedure. There were 13 deaths (90.3/1000 procured abortions) in this series. 77 of the abortion patients were teenagers; another 35 were 20-24 years old. Teenagers were more likely than women in the older age groups to obtain their abortion in the second trimester of pregnancy. 85 women were single. Major occupations represented in the group included students (32 women), house girls/maids (23 women), and business/trading (20 women). The desire to remain in school or retain employment were the reasons most commonly cited for terminating the pregnancy. Sepsis occurred in 39 women, while 18 experienced hemorrhagic anemia. The causes of death included generalized septicemia (3 cases), sepsis with anemia (3 cases), sepsis with jaundice (2 cases), peritonitis with abscess (2 cases), uterine perforation with peritonitis (2 cases), and endotoxic shock (1 case). The maternal mortality and morbidity associated with illegal abortion in Nigeria suggest a need to make family planning services more available to adolescents and single women and to ensure that the scope of family life education is expanded.
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PMID:Procured abortion in Ilorin, Nigeria. 749 12

Endotoxic shock is associated with a coagulopathy, organ failure, and death. Tissue factor (TF) expression by monocytes exposed to bacterial endotoxin (lipopolysaccharide [LPS]) may mediate the coagulopathy and contribute to the high mortality of this disease. We examined the role of the LPS-binding protein (LBP)/CD14 receptor pathway in the LPS induction of TF expression in human monocytic THP-1 cells and peripheral blood monocytes. In THP-1 cells, the threshold concentration of LPS required to induce TF activity in serum-free medium was reduced 20-fold by purified LBP, which also enhanced TF mRNA synthesis. Similarly, monocytes cultured in the presence of serum were induced to express TF antigen at LPS concentrations 100 times lower than monocytes cultured in serum-free medium. An anti-LBP monoclonal antibody indicated that this effect was dependent on the presence of LBP in serum. LPS/LBP induction of TF activity and TF antigen expression in these monocytic cells were also inhibited by an anti-CD14 monoclonal antibody, indicating a requirement for the CD14 receptor. Thus, we suggest that low levels of LPS (5 to 100 pg/mL) present during sepsis induce TF expression in monocytes via the LBP/CD14-dependent pathway.
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PMID:Role of the lipopolysaccharide (LPS)-binding protein/CD14 pathway in LPS induction of tissue factor expression in monocytic cells. 751 85

Inhibitors of nitric oxide (NO) synthesis have been used in the treatment of septic and endotoxic shock. However, several studies question the beneficial effect of inhibiting NO production in sepsis and endotoxemia. We have investigated the effect of inhibition of NO synthesis after endotoxemia in the isolated perfused rat heart. In hearts from endotoxin-treated animals, coronary flow was elevated 64% and oxygen consumption was elevated 20% compared with control hearts. NADH fluorescence imaging was used as an indicator of regional hypoperfusion. A homogeneous low-surface NADH fluorescence, indicative of adequate tissue perfusion, was observed in both control and endotoxin-treated hearts. The increase in coronary flow and oxygen consumption could only partially be prevented by pretreatment of the animals with dexamethasone. Addition of N omega-nitro-L-arginine (NNLA), an inhibitor of NO synthesis, to the perfusion medium eliminated differences in coronary flow and oxygen consumption between normal and endotoxin-treated hearts. However, NADH surface fluorescence images of endotoxin-treated hearts after NNLA revealed areas of high fluorescence, indicating local ischemia, whereas the control hearts remained without signs of ischemia. The ischemic areas were present at various perfusion pressures and disappeared after the infusion of L-arginine, the natural precursor of NO, or the exogenous NO donor sodium nitroprusside. Methylene blue (MB), an inhibitor of soluble guanylate cyclase, the effector enzyme of NO, also eliminated differences in coronary flow and produced similar areas of local myocardial ischemia in endotoxin-treated hearts but not in control hearts.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibition of nitric oxide synthesis causes myocardial ischemia in endotoxemic rats. 753 18

The results of early studies suggest that nitric oxide (NO) synthesis inhibition may be therapeutic in sepsis, but recent data indicate that NO inhibition may be harmful. This study investigates the effects of NO synthesis inhibition with N-nitro-L-arginine methyl ester (NAME) on regional blood flow following endotoxemia. Anesthetized, instrumented swine were randomly divided into four groups. Controls received normal saline resuscitation (NSR) at 1 cc/kg/min beginning at T0. The lipopolysaccharide group (LPS) received NSR and Escherichia coli LPS, 200 micrograms/kg at T0. The LPS+NAME group received NSR and LPS at T0, plus NAME (50 micrograms/kg/min) starting at T1. The NAME group received only NSR and NAME. Hemodynamic data, regional blood flow, and gastric intramucosal pH (pHi) were measured hourly. LPS increased renal and carotid blood flow consistent with a hyperdynamic state. Mesenteric blood flow was decreased. Treatment of endotoxic animals with NAME decreased renal and carotid blood flow. Mesenteric blood flow and gastric pHi were improved by NAME. NO inhibition in endotoxic shock results in decreased carotid and renal blood flow, by decreasing cardiac output. Mesenteric blood flow and perfusion were improved; however, this requires further study for validation.
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PMID:Effects of nitric oxide synthase inhibition on regional blood flow in a porcine model of endotoxic shock. 754 64

Heme oxygenase (HO) catalyzes the rate-limiting step in the degradation of heme to bilirubin. HO-1 is highly induced by heme, its major substrate, and nonheme products, including metal ions and hormones. Interest in HO-1 has been stimulated recently by observations that HO-1 is also highly induced in response to oxidative stress in vitro. The physiologic significance of HO-1 induction following oxidant injury in vivo, however, is poorly understood. In a rat model of lipopolysaccharide endotoxin (LPS)-induced lung injury and sepsis, we demonstrate that the lung responds to LPS by expressing high levels of HO-1 mRNA and enzyme activity. We hypothesize that this HO-1 induction could play a critical role in the lung's defense against LPS. Pretreatment of rats with hemoglobin, a potent inducer of HO-1, resulted in HO-1 induction and more importantly provided complete protection against subsequent lethal endotoxemia (100% survival). Tin protoporphyrin, a competitive inhibitor of HO, blocked this protective effect of hemoglobin and rendered the rats more susceptible to a lethal dose of LPS. Taken together, these data strongly implicate HO-1 in playing an important role in the defense against endotoxic shock, with potential therapeutic implications.
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PMID:Hemoglobin provides protection against lethal endotoxemia in rats: the role of heme oxygenase-1. 757 96

The incidence of sepsis in the United States has risen in the past few years, and mortality from sepsis has risen over the past several decades. These increases have occurred despite the progress made in antibiotic therapy. The high mortality rate may not be related to the bacteria themselves but rather to the host's response. Of particular concern is the bacterial release of endotoxins, the development of endotoxic shock, and the resulting multiorgan failure, which has a high fatality rate and is the leading cause of death in patients admitted to intensive care units. Removing or neutralizing endotoxins are the two major therapeutic approaches to treating sepsis. To date, pharmacological methods have not been successful. Extracorporeal techniques are based on filtration, sorption, or both. Results with hemofiltration have not been definitive, in part because endotoxin levels have not been measured. Sorption devices, based on polymyxin B and anion exchange matrices, do remove endotoxins. Clinical studies in Japan on septic shock or multiorgan failure with polymyxin-B-bound fibers in direct hemoperfusion continue to suggest the utility of extracorporeal techniques for endotoxin removal. Continued effort is required and warranted to assess the clinical efficacy of these techniques.
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PMID:Extracorporeal techniques of endotoxin removal: a review of the art and science. 761 38

Disseminated intravascular thrombosis is a frequent complication of endotoxic shock, and modulation of endothelial cell hemostatic properties has been proposed to play a role in its pathogenesis based on studies of endothelial cells in culture. This study examined the in vivo expression of tissue factor (TF) and thrombomodulin (TM) in a baboon model of lethal Escherichia coli sepsis using immunohistochemistry with monospecific antibodies. Expression of E-selectin (E-sel) was also determined as a marker of endothelial cell activation. Correlation of immunoreactivity with procoagulant activity in lipopolysaccharide-stimulated cultured human endothelial cells showed that immunohistochemistry was sufficiently sensitive to detect as little as 5% of the maximum in vitro endothelial cell TF response. Vascular endothelium of control animals expressed TM but had no detectable TF or E-sel. Following E. coli infusion, widespread E-sel expression and microvascular fibrin deposition was evident within 6 hours. However, expression of TF by endothelial cells became detectable only in the splenic microvasculature, where endothelial specificity of TF expression was confirmed by dual immunofluorescence of TF with von Willebrand's factor and with TM. In the spleen, there was a dissociation of expression of TF and E-sel, with marginal zone vessels being TF-positive and E-sel-negative, whereas sinusoidal endothelium was E-sel-positive but TF-negative. TM expression was unchanged from controls. Additionally, expression of TF by lung alveolar epithelial cells, splenic macrophages, and epithelial cells of the renal glomeruli was observed to be enhanced in septic animals. This study documents endothelial cell expression of TF in vivo in a relevant pathological setting. At the same time, compared with endothelial cells in culture, there is in vivo both significantly greater control of TF expression than expected, given the strong positive stimuli present in lethal E. coli septic shock and an unpredicted heterogeneity of activation responses.
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PMID:Expression of tissue factor, thrombomodulin, and E-selectin in baboons with lethal Escherichia coli sepsis. 768 96

Vascular endothelial cell (EC) injury by lipopolysaccharides (LPS) plays a major role in the pathogenesis of gram-negative bacterial sepsis and endotoxic shock. The studies described here were performed to define further the molecular mechanisms involved in the EC responses to LPS. We showed that serum was required for LPS-mediated cytotoxicity for bovine brain microvessel, pulmonary, and aortic ECs and that anti-human CD14 antibodies completely blocked LPS-mediated cytotoxicity for ECs in the presence of human serum. The addition of a recombinant soluble form of human CD14 to serum-free medium restored the LPS-mediated cytotoxicity, whereas the addition of LPS binding protein (LBP), a serum protein that potentiates LPS-induced responses to monocytes, had no effect. A similar dependency on serum or recombinant soluble CD14 (under serum-free conditions) was observed for LPS-induced secretion of interleukin-6 by human umbilical vein ECs. These findings indicate that soluble CD14 is required for LPS-mediated EC responses independently of LPB, suggesting that serum soluble CD14 represents a naturally occurring agonist for EC responses to LPS.
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PMID:Endotoxin-mediated endothelial cell injury and activation: role of soluble CD14. 768 81

Evidence of a role for oxygen-derived free radicals in the pathophysiology of endotoxic shock has been found in animal models. However, the importance of free radicals in chronic models of bacterial infection has not been examined. In this study a novel nitrone radical spin trap is described and its activity in animal models of endotoxic shock and chronic bacteremia were explored. MDL 101,002 is a cyclized variant of alpha-phenyl N-tert-butyl nitrone (PBN), an established spin trap. MDL 101,002 can react with free radicals to form persistent adducts as demonstrated by electron paramagnetic resonance (EPR) spectroscopy. This agent is about 10 times more potent than PBN as an in vitro antioxidant and scavenger of hydroxyl radicals. In a rat endotoxic shock model MDL 101,002 (3-30 mg/kg, i.p.) administered 30 min prior to endotoxin (30 mg/kg, i.p.) treatment reduced mortality in a dose-dependent manner. Peroxide-enhanced chemiluminescence in hepatic homogenates from endotoxin treated rats was elevated indicating that oxidative stress and antioxidant depletion was increased. Importantly, treatment with MDL 101,002 (30 mg/kg, i.p.) 30 min prior to, and 120 min following endotoxin, minimized the increase in chemiluminescence. MDL 101,002 also reduced mortality in a model of chronic bacteremia employing implantation of infected fibrin clots into the peritoneal cavity of gentamicin-treated leukopenic rats. MDL 101,002 (2.5 mg/kg/hr) increased survival from 24% to 52% in these rats. These data are consistent with a role for free radicals in the pathophysiology of endotoxic shock and suggest free radicals are also important mediators in chronic models of sepsis.
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PMID:Protective effects of a cyclic nitrone antioxidant in animal models of endotoxic shock and chronic bacteremia. 785 Sep 33


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