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)

The effects of a preparative dose of the leukocyte egesta containing degraded meningococci and a provocative dose of the meningococcal lipopolysaccharide on development of pathological lesions associated with disseminated intravascular coagulation were studied in tissues of 32 rabbits. These effects were compared with effects of a single dose of meningococcal lipopolysaccharide as well as leukocyte egesta containing degraded Staphylococcus epidermidis. Rabbits injected subcutaneously with egesta containing degraded meningococci followed after 12 h with meningococcal endotoxin (intravenously) exhibited heterophilic leukocytosis and disseminated intravascular coagulation mainly in the pulmonary capillaries and venules; focal necroses occurred in myocardium, lungs, and liver, whereas, cortical renal necrosis developed in lethal cases. Similar lesions, however, but less severe and with less frequency, developed even after a single dose of meningococcal endotoxin or after endotoxin that followed a dose of supernatant fluid from normal leukocytes. Our findings suggest that meningococcal material from polymorphonuclear degradation plays a role in the pathology characteristic of meningococcal septicemia.
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PMID:Pathology in rabbits treated with leukocyte-degraded meningococci in combination with meningococcal endotoxin. 40 2

We have studied the role of complement in lipopolysaccharide (LPS)-induced hypotension and disseminated intravascular coagulation (DIC) by comparing the effects of injection of three preparations of LPS from E. Coli 0111:B4, S. minnesota Re595, and S. marcescens. Injections of nonlethal doses of these LPS preparations into normal rabbits produced decreases in mean arterial blood pressure during a 5-h period. When rabbits treated with cobra venom factor (CoF) to deplete C3 were injected with the various LPS preparations, mean arterial pressures fell at a rate and extent essentially identical to that observed in normal rabbits. Rabbits genetically deficient in C6 also demonstrated LPS-induced hypotensive changes. Only minimal, or no changes in plasma C3 levels or serum CH50 values were detected in normal rabbits after LPS injection. Hypotensive changes were also induced in rabbits when complement was rapidly activated by intravenous injection of CoF. In contrast to the hypotension induced by LPS, the fall in arterial pressure associated with the consumption of complement was short lived and required the rapid consumption of considerable amounts of C3. The occurrence of DIC noted in normal rabbits injected with each preparation of LPS was not inhibited in either rabbits treated with cobra factor or in C6-deficient rabbits. The DIC was most pronounced after injection of Re595 and S. marcescens LPS. Injection of the various LPS preparations produced a rapid disappearance of circulating neutrophils and mononuclear cells, which occurred with the same kinetics and to the same extent in normal, CoF-treated, and C6-deficient rabbits. Injection of either Re595 LPS or S. marcescens LPS produced a biphasic disappearance of circulating 51Cr-platelets. In contrast, injection of 0111:B4 LPS affected only slightly the rate of disappearance of 51Cr-platelets. Depletion of C3 by cobra factor treatment had no effect on the disappearance of platelets in animals injected with 0111:B4. In marked contrast cobra factor treatment greatly reduced the initial rapid disappearance of platelets in rabbits injected with either Re595 or S. marcescens LPS, but had no effect in the secondary disappearance phase.
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PMID:Mediation systems in bacterial lipopolysaccharide-induced hypotension and disseminated intravascular coagulation. I. The role of complement. 110 50

Changes in the plasma thrombomodulin (TM) level were examined in endotoxin-infused rabbits. The plasma TM level in normal rabbits was 143.8 +/- 8.4 ng/ml (n = 67) and the molecular weight of the major TM was about 55 kd. Endotoxin (lipopolysaccharide, LPS, E. Coli B8:0127) was intravenously infused. LPS infusion increased the plasma TM level dose-dependently between 0.2 mg/kg and 5 mg/kg. When 5 mg/kg LPS was infused, the plasma TM level started to increase immediately and was 2.3 times higher than the control value within 1 hr. The molecular weight of the major TM was about 75 kd. This rapid increase in TM occurred before the decrease in fibrinogen content and the prolongation of prothrombin time. To examine the effect of circulating leukocytes on the TM increase in endotoxin-infused rabbits, 5 mg/kg LPS was infused into rabbits with leukocytopenia induced by X-ray irradiation. The maximum plasma level of TM was significantly lower than in the untreated rabbits given LPS. These data suggest that the increase in plasma TM is caused by LPS-stimulated leukocyte's prior to hemostaseological changes. It is well known that endothelial cells can be injured by stimulated leukocytes, so this increase in plasma TM probably reflects the deterioration of endothelial cells. This deterioration decreases the ability of endothelial cells to inhibit thrombosis, which would, in turn, contribute to the development of disseminated intravascular coagulation in endotoxin-infused rabbits.
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PMID:Changes in thrombomodulin level in plasma of endotoxin-infused rabbits. 131 90

Thrombomodulin (TM) is an endothelium-associated glycoprotein that converts thrombin from a procoagulant protease to an anticoagulant. Thrombin, a key enzyme in thrombus formation, binds to TM molecules on endothelium with very high affinity. After binding to TM, thrombin fails to act on the coagulation factors and platelets, and its ability to activate protein C is enhanced more than 1000-fold. We expressed soluble recombinant TM (rTM) in CHO cells and evaluated its antithrombotic effect on thrombin-induced thromboembolism in mice and lipopolysaccharide (LPS) induced disseminated intravascular coagulation (DIC) in rats. Thrombin injection into mouse caused acute thromboembolism resulting instantaneous death, however preinjection of rTM neutralized the lethal effect of thrombin in a dose-dependent manner. Soluble rTM also improved the consumption of fibrinogen and platelets in experimental DIC-rats induced by LPS. The effect of rTM was confirmed in histologically. These data suggest that rTM may have a therapeutic effect on thrombosis or DIC in human.
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PMID:[Therapeutic evaluation of recombinant thrombomodulin]. 133 21

We have evaluated the effect of 1-Deamino-8D-arginine vasopressin (DDAVP) on an experimental model of intravascular coagulation (DIC) induced in rabbits by injection of 20 micrograms kg-1 h-1 during 6 h of E. coli lipopolysaccharide. DDAVP significantly ameliorated the platelet drop and fibrinogen decrease (p less than 0.01) induced by endotoxin in control animals. A significant reduction in factor XII consumption (p less than 0.01) and a decrease in the generation of endotoxin induced PAI-1 activity in rabbits circulation was also observed (p less than 0.005). Moreover, fibrin deposition in kidneys of rabbits receiving DDAVP was significantly reduced as compared to control animals. Finally, the mortality rate in the control group was significantly higher than in DDAVP-treated rabbits (p less than 0.01). The hemostatic changes induced by DDAVP correlated with lower fibrin deposition and reduction in mortality rates.
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PMID:Effect of DDAVP on endotoxin-induced intravascular coagulation in rabbits. 144 Apr 97

Experimental generalized Shwartzman reaction (GSR) in animals can be induced by systemic injection of bacterial endotoxin lipopolysaccharide (ET) and presents with thrombotic occlusions of small blood vessels in different organs analogous to disseminated intravascular coagulation (DIC) in man. It is known that DIC involvement of the central nervous system (CNS) in man presents with grave prognosis, but there is a paucity of information concerning CNS involvement in animals with ET induced GSR. In order to better understand the pathogenesis of CNS involvement of DIC in man, and to search for better prophylactic and therapeutic measures against DIC, animal model of DIC was induced by continuous intravenous infusion of E coli ET. A total of 56 male Donryu rats were divided into 6 groups and infused with physiologic saline (controls) and ET lipopolysaccharide at 88.5 micrograms/hour. The rats were killed at 6 different intervals from 24 to 160 hours and examined postmortem. Intracerebral hemorrhagic lesions were seen in 2 of 7 rats (29%) as early as 24 hours of ET-infusion and increased to 77% to 87% of rats receiving continuous ET infusion up to 160 hours. Formation of fibrin thrombi was uncommon in intracerebral blood vessels, but it was frequently observed in choroid plexus capillaries. Fibrin thrombi in other viscera (heart, lungs, liver, kidneys, spleen) were common but decreased toward the end of 160-hour infusion period. Results of this study showed that a continuous intravenous infusion of large dose ET lipopolysaccharide in rats produces intracerebral hemorrhagic lesions analogous to DIC changes of brain seen in man.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Brain injury induced by continuous infusion of endotoxin (ET) in rat--relationship between ET infusion hours and development of cerebral and visceral lesions]. 156 32

Antithrombotic effect of recombinant human thrombomodulin (TM) on experimentally induced thrombosis in mice was studied. The soluble recombinant human TM (TMD 123), which was expressed in Chinese hamster ovary cells and purified from the conditioned medium, prolonged thrombin clotting time for mouse plasma in a dose-dependent fashion. Thrombosis was induced by the injection of lipopolysaccharide (LPS) from E. coli into a lateral tail vein of mice and was identified as disseminated intravascular coagulation (DIC) syndrome by hematological and histological examinations. Simultaneous injection of TMD 123 with LPS into another lateral tail vein of mice significantly corrected the hematological abnormalities compatible with DIC, and also corrected the histological abnormalities i. e. fibrin deposition and decrease of cellular TM in the target organs including kidney, liver and lung. These results indicate that recombinant human TM is a potent antithrombotic agent and that this would be an expectative anticoagulant for DIC or thrombosis in man.
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PMID:[Antithrombotic effect of recombinant human thrombomodulin on experimentally induced thrombosis in rats]. 165 29

The most frequent cause of toxic shock in our area is meningococcal sepsis. It is currently assumed that endotoxin produce by this bacteria, a lipopolysaccharide with toxic properties, is able to trigger shock and DIC by stimulating both arachidonic acid pathways, among other actions. Previous studies in our laboratory demonstrated significant differences (p +/- 0.001) in the amounts of endotoxins released in vitro by strains from patients and healthy carriers and statistically related criteria of severity with mortality in 256 patients in our center over the last 10 years. In the present study we attempted to establish whether plasma levels of endotoxin were correlated with the severity of the disease. We studied 32 patients with meningococcal sepsis, dividing the subjects into two groups: those in whom six or more criteria of severity were present, and those in whom less than six criteria were found. Blood levels of endotoxin were determined upon admission and after the administration of antibiotics (penicillin and chloramphenicol) using the limulus test with a chromogenic substrate (Coatest, Endotoxin, Kabivitrum, Sweden). Levels of endotoxins were significantly higher in patients with more than six criteria of severity both upon admission (0.6 +/- 0.03) ng/ml) and 4 h. afterward (0.74 +/- 0.006 ng/ml) in comparison to children in whom the clinical picture was less serious (0.27 +/- 0.18 ng/ml and 0.27 +/- 0.18 ng/ml and 0.27 +/- 0.16 ng/ml7 t = 5.8 y t = 5.6 respectively. Endotoxin levels were highest in patients presenting shock, disseminated intravascular coagulation in the hypocoagulability phase and more than 8 criteria.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Studying the levels of endotoxemia in meningococcal sepsis. Its relations to pregnancy and antibiotic treatment]. 188 9

The plasma level of interleukin-1 beta (IL-1 beta) was determined in normal individuals, patients with disseminated intravascular coagulation (DIC), patients in the pre-DIC period (within 7 days before the onset of DIC), and non-DIC patients to examine the relationship between DIC and the plasma IL-1 beta level. The plasma IL-1 beta level was 0-0.085 ng/ml in normal individuals, with little difference being seen according to related age. It was significantly higher in the DIC group (0.19 +/- 0.19 ng/ml) than in the pre-DIC group (0.05 +/- 0.08 ng/ml) or the non-DIC group (0.09 +/- 0.01 ng/ml). The plasma IL-1 beta level was not markedly elevated in leukemia patients, even in the DIC group, but it was significantly increased in the DIC group of solid cancer patients and was generally elevated in patients with sepsis. It was markedly elevated to 0.39 +/- 0.26 ng/ml in patients with organ failure. When mononuclear cells were incubated with lipopolysaccharide, it was found that IL-1 beta, tumor necrosis factor, and tissue factor (TF) were released into the medium, and there was an increase of TF release from endothelial cells incubated with this medium. These results suggest that the increase in IL-1 beta reflected the activation of monocytes and may be an important factor in DIC and its associated organ failure.
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PMID:Plasma level of IL-1 beta in disseminated intravascular coagulation. 205 18

To clarify whether activated platelets play an important role in the occurrence and exacerbation of disseminated intravascular coagulation (DIC), we investigated the effects of 4 anti-platelet drugs, a PGI2 analog (CS-570), a thromboxane synthetase inhibitor (dazoxiben), a thromboxane receptor antagonist (BM-13177), and ticlopidine, in an experimental DIC model in rats. Experimental DIC was induced by a continuous infusion of lipopolysaccharide (LPS derived from E. coli, 055 B5, 25 mg/kg/hr) for 4 hrs. In the time-course determination of the coagulation parameters and prostanoids, an abrupt increase in TxB2 (a stable metabolite of TxA2) and 6-keto-PGF1 alpha (a stable metabolite of PGI2) was followed by a decrease in platelet count, a prolongation of blood coagulation time, and an increase in fibrinogen/fibrin degradation products (FDP). Four hours after the start of LPS infusion, the rats were considered to be in the state of DIC. The effects of the anti-platelet drugs were investigated 4 hrs after the start of LPS infusion. CS-570 and ticlopidine ameliorated DIC in a dose-dependent manner. CS-570 (10 micrograms/kg/min) improved DIC in the platelet count, prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (Fbg), and FDP, without affecting TxB2 and 6-keto-PGF1 alpha formation. Ticlopidine (200 mg/kg, i.p.) prevented the exacerbation of DIC in such item parameters as platelet count, APTT, and FDP. Both dazoxiben and BM-13177 (30 mg/kg, i.p.) ameliorated DIC in following parameters as platelet count, APTT and FDP. Dazoxiben, but not BM-13177, significantly inhibited the increase in TxB2 concentration at 4 hr. These observations suggest that drugs which inhibit platelet activation by a TxA2-dependent route are effective in improving DIC induced by LPS, and that drugs which inhibit multiple platelet-activating routes improve DIC in more item parameters than drugs which inhibit only the TxA2-dependent activating route. Consequently, it is concluded that activated platelets might play an important role in the occurrence and exacerbation of DIC induced by LPS, and that one of the roles of TxA2 in DIC is to activate platelets.
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PMID:Role of activated platelets in endotoxin-induced DIC in rats. 208 Apr 92


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