Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0012739 (disseminated intravascular coagulation)
 8,673 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

ABT-299, a highly potent and selective platelet activating factor (PAF) antagonist, was found to be effective in rat models of endotoxic shock. ABT-299 inhibited and reversed LPS-induced hypotension (ED50 of .008 mg/kg, intraarterially). When given prior to LPS challenge, ABT-299 (.1 mg/kg, intravenously) completely inhibited LPS-induced intestinal damage for as long as 8 h after the administration of the antagonist. Pretreatment of rats with ABT-299 (5 mg/kg, intravenously over 4 h) prevented by 85-95% symptoms of disseminated intravascular coagulation (DIC) induced by LPS, including thrombocytopenia, prolongation of prothrombin and partial thromboplastin time, decreased serum fibrinogen, and elevation of serum fibrinogen/fibrin degradation products. A .1 mg/kg dose of ABT-299 administered orally or intravenously improved long-term survival to 80% and 90%, respectively, following a lethal dose (LD65) of LPS. ABT-299 (.1 mg/kg) was also effective in preventing hypotension and gastrointestinal damage induced by lipoteichoic acid (LTA), a putative causative agent of shock in Gram-positive infections. These results illustrate the impressive potency and duration of action of ABT-299 and support the putative role of PAF in acute models of endotoxic shock.
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PMID:ABT-299, a novel PAF antagonist, attenuates multiple effects of endotoxemia in conscious rats. 885 45

A large animal model of fulminant hepatic necrosis is necessary to test the efficacy of artificial liver support systems. A recent model was developed using D-galactosamine in anesthetized dogs. Because of the difficulties encountered with prolonged anesthesia, a similar protocol was used in 10 unanesthetized dogs. Intravenous infusions of D-galactosamine (1.0 to 1.5 gm/kg) did not result in uniform death of all animals at 72 hours or development of hypoglycemia. Severe hepatic necrosis was observed in all animals, but residual hepatocyte viability was evident in some. All animals developed severe consumption coagulopathy with histological evidence of disseminated intravascular coagulation (DIC) in four. A clinical picture characteristic of endotoxic shock was observed in most animals as a terminal event. The presence of endotoxin was confirmed in all dogs tested after 12 hours (7/10). The differences observed between this model and the anesthetized model are probably because of the toxic synergism between halothane and D-galactosamine. Neither model seems satisfactory for the testing of artificial liver support systems. The halothane model requires extremely long periods of anesthesia and mechanical ventilation. The present model does not cause uniform or universal death of the animals within 3 days. Foremost, both models result in DIC and endotoxic shock, neither of which is likely to respond to bioartificial liver support or treatment with conventional dialysis membranes.
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PMID:Galactosamine-induced fulminant hepatic necrosis in unanesthetized canines. 936 88

In rats with 2-week obstructive jaundice the sensitivity to endotoxin was studied and the effect of a single dose of endotoxin on histological development in the kidney, liver and spleen was also investigated. We were tested the effect on accumulation and distribution within organs, of fibrinogen labelled with radioactive iodine I 125. We showed an increased sensitivity to endotoxin in obstructive jaundice. The cause of death in most rats was acute circulatory failure during the course of endotoxic shock, without clinical features of disseminated intravascular coagulation. In the isotope study, after endotoxin administration there was a specific dynamic increase of fibrinogen accumulation in the kidneys of rats with obstructive jaundice. We proposed, that the cause of the kidney changes during the course of obstructive jaundice could be the local activation of intrarenal coagulation.
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PMID:The role of endotoxaemia in the development of renal disorders in experimental obstructive jaundice in rats. 918 46

UR-12670 is a novel and potent PAF antagonist, eg., it displaces [3H]WEB-2086 from PAF receptors in rabbit platelet membranes (Ki = 0.6 nM) and inhibits PAF-induced increase in vascular permeability in rat trachea (100%), thymus (44%), seminal vesicles (100%) and stomach (54%) at a dose of 0.01 mg/kg i.v. Since PAF is thought to be an important mediator in endotoxic shock, the effect of pretreatment with UR-12670 on changes in vascular permeability, disseminated intravascular coagulation (DIC) and plasma biochemical parameters were determined in a rat model of acute endotoxemia. UR-12670 and the reference PAF antagonist, lexipafant (10 mg/kg i.v.), strongly inhibited lipopolysaccharide (LPS, 25 mg/kg i.v.)-induced plasma leakage in the trachea (49 and 100%, respectively) and seminal vesicles (81 and 100%), as assessed by the Evans blue extravasation method. Only lexipafant inhibited the increase in vascular permeability in the thymus (36%). Neither PAF antagonist was effective in the stomach. Both UR-12670 and lexipafant at 10 mg/kg i.v. attenuated the LPS-induced variation of some DIC markers, such as activated partial thromboplastin time increase (56 and 58%, respectively) and the fibrinogen concentration decrease (53 and 31%), whereas the increase in prothrombin time was not affected. Increased plasma acid phosphatase (ACP, a lysosomal activation marker) and lactate dehydrogenase (LDH, a tissue damage marker) activity elicited by LPS was attenuated by pretreatment with 10 mg/kg i.v. of either UR-12670 or lexipafant (ACP: 55 and 48%; LDH: 50 and 33%). LPS-induced hyperglycemia (46 and 37%) and hyperlactacidemia (100% both) were also inhibited. UR-12670 protected against several shock symptoms, confirming the role of PAF in the pathogenesis of rodent endotoxemia.
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PMID:Effects of a new platelet-activating factor antagonist, UR-12670, on several endotoxic shock markers in rats. 951 29

A 60-year-old woman undergoing surgery died from endotoxic shock and DIC after receiving a 19-day-old unit of optimal additive red-cell concentrate found contaminated with Serratia liquefaciens. No source of contamination could be found. This normally free-living organism is usually of low pathogenicity. It is a very unusual contaminant of stored donated blood, although it appears to be on the increase. When transfused, blood contaminated with S. liquefaciens always causes severe morbidity and is associated with a high death rate. This is the fifth report in the English literature.
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PMID:Fatal reaction to transfusion of red-cell concentrate contaminated with Serratia liquefaciens. 956 51

Endotoxic shock with multiorgan dysfunction syndrome (MODS) is fatal in more than 80% of cases and is the leading cause of death in patients admitted to intensive care units. The incidence has increased to more then 100% in the last 10 years and there has been no significant decreases in its morbidity and mortality. The systemic inflammatory response to infection, e.g. sepsis, develops when the endotoxins activate various cascade systems. The activation of the cascade systems triggers further release of various active substances and cytokines. The progress may result in consumption coagulopathy, which may further generate an acute septic shock, disseminated intravascular coagulation, and MODS. When more than 3 organs are involved, the risk of fatal outcome exceeds 80%. The use of plasma exchange may be a beneficial adjunct to therapy during a progressive septic shock with MODS, when the patient does not respond to classical intensive care unit therapy. The beneficial effect, recently reported for plasma exchange procedures in patients with sepsis, may be due to the removal of various toxins and waste products from the blood, and administration of plasma from healthy subjects.
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PMID:Therapeutic plasma exchange in severe sepsis or septic shock. 968 1

The influence of social disruption stress (SDR) on the susceptibility to endotoxic shock was investigated. SDR was found to increase the mortality of mice when they were challenged with the bacterial endotoxin lipopolysaccharide (LPS). Histological examination of SDR animals after LPS injection revealed widespread disseminated intravascular coagulation in the brain and lung, extensive meningitis in the brain, severe hemorrhage in the lung, necrosis in the liver, and lymphoid hyperplasia in the spleen, indicating inflammatory organ damage. In situ hybridization histochemical analysis showed that the expression of the glucocorticoid receptor mRNA was down-regulated in the brain and spleen of SDR animals while the ratio of expression of AVP/CRH-the two adrenocorticotropic hormone secretagogue, increased. After LPS injection, the expression of pro-inflammatory cytokines, IL-1beta and TNF-alpha, was found significantly higher in the lung, liver, spleen, and brain of the SDR mice as compared with the LPS-injected home cage control animals. Taken together, these results show that SDR stress increases the susceptibility to endotoxic shock and suggest that the development of glucocorticoid resistance and increased production of pro-inflammatory cytokines are the mechanisms for this behavior-induced susceptibility to endotoxic shock.
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PMID:Social stress increases the susceptibility to endotoxic shock. 1128 52

The effect of porins, major hydrophobic outer membrane proteins purified from Salmonella typhimurium, on human blood coagulation was investigated. It was found that micromolar concentrations of porins accelerated markedly human blood coagulation in vitro. Using appropriate experiments, data were obtained showing that the main target of the porin-induced procoagulant effect was thrombin. A possible binding of porins with thrombin has been suggested to be the basis of this effect. The implications of this finding in the pathogenesis of the disseminated intravascular coagulation syndrome (DIC) occurring during the Gram-negative septic shock is discussed.
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PMID:Porins from Salmonella typhimurium accelerate human blood coagulation in vitro by selective stimulation of thrombin activity: implications in septic shock DIC pathogenesis. 1158 72

Endotoxic shock, one of the most prominent causes of mortality in intensive care units, is characterized by pulmonary hypertension, systemic hypotension, heart failure, widespread endothelial activation/injury, and clotting culminating in disseminated intravascular coagulation and multi-organ system failure. In the last few years, studies in rodents have shown that administration of low concentrations of carbon monoxide (CO) exerts potent therapeutic effects in a variety of diseases/disorders. In this study, we have administered CO (one our pretreatment at 250 ppm) in a clinically relevant, well-characterized model of LPS-induced acute lung injury in pigs. Pretreatment only with inhaled CO significantly ameliorated several of the acute pathological changes induced by endotoxic shock. In terms of lung physiology, CO pretreatment corrected the LPS-induced changes in resistance and compliance and improved the derangement in pulmonary gas exchange. In terms of coagulation and inflammation, CO reduced the development of disseminated intravascular coagulation and completely suppressed serum levels of the proinflammatory IL-1beta in response to LPS, while augmenting the anti-inflammatory cytokine IL-10. Moreover, the effects of CO blunted the deterioration of kidney and liver function, suggesting a beneficial effect in terms of end organ damage associated with endotoxic shock. Lastly, CO pretreatment prevents LPS-induced ICAM expression on lung endothelium and inhibits leukocyte marginalization on lung parenchyma.
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PMID:Carbon monoxide pretreatment prevents respiratory derangement and ameliorates hyperacute endotoxic shock in pigs. 1622 83

The spectrum of kidney disease occurring during pregnancy includes preeclampsia, hypertensive disorders of pregnancy, urinary tract infection, acute kidney injury, and renal cortical necrosis (RCN). Preeclampsia affects approximately 3-5% of pregnancies. We observed preeclampsia in 5.8% of pregnancies, and 2.38% of our preeclamptic women developed eclampsia. Severe preeclampsia and the eclampsia or hemolysis, elevated liver enzymes levels, and low platelets count (HELLP) syndrome accounted for about 40% of cases of acute kidney injury (AKI) in pregnancy. Preeclampsia/eclampsia was the cause of acute renal failure (ARF) in 38.3% of the cases. Preeclampsia was the most common (91.7%) cause of hypertension during pregnancy, and chronic hypertension was present in 8.3% of patients. We observed urinary tract infection (UTI) in 9% of pregnancies. Sepsis resulting from pyelonephritis can progress to endotoxic shock, disseminated intravascular coagulation, and AKI. The incidence of premature delivery and low birth weight is higher in women with UTI. The incidence of AKI in pregnancy with respect to total ARF cases has decreased over the last 30 years from 25% in 1980s to 5% in 2000s. Septic abortion-related ARF decreased from 9% to 3%. Prevention of unwanted pregnancy and avoidance of septic abortion are key to eliminate abortion-associated ARF in early pregnancy. The two most common causes of ARF in third trimester and postpartum periods were puerperal sepsis and preeclampsia/HELLP syndrome. Pregnancy-associated thrombotic thrombocytopenic purpura/hemolytic uremic syndrome and acute fatty liver of pregnancy were rare causes of ARF. Despite decreasing incidence, AKI remains a serious complication during pregnancy.
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PMID:The kidney in pregnancy: A journey of three decades. 2308 48


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