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Query: UMLS:C0012739 (disseminated intravascular coagulation)
 8,673 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tissue factor (TF) and lipopolysaccharide (LPS) are frequently used to induce disseminated intravascular coagulation (DIC) in experimental animal models. Although the pathophysiology of DIC may differ depending on which agent is used for induction, previous studies on models of DIC have not distinguished which DIC-inducing agent was used. In the present paper, we evaluate the characteristics of TF-induced and LPS-induced DIC using two types of DIC models, with special reference to selected hemostatic parameters and pathological findings within the kidney. Male Wistar rats were administered TF (3.75 U/kg; sustained infusion for 4 h) or LPS (30 mg/kg; sustained infusion for 4 h) via the tail vein, and blood sampling was performed at 0, 1, 3, 4, 5, 7, 9, 11, and 28 h. Judging from changes in the levels of thrombin-antithrombin complex, fibrinogen levels, and platelet counts, it is reasonable to conclude that the severity of both types of experimental DIC is similar with regard to hemostatic activation and consumption coagulopathy. A marked elevation in the level of D-dimer was noted without any organ dysfunction or much fibrin deposition in the kidney upon administration of TF. However, a markedly prolonged period of elevation in plasminogen activator inhibitor activity, a prolonged depression in antithrombin III activity, severe organ failure, and a markedly prolonged period of fibrin deposition in the kidney was observed following LPS administration. A modest number of the rats from the TF-induced DIC model died during the experimental period, whereas a large number of rats died during LPS-induced DIC, especially after 9 h. Since the time course of the pathophysiology differed remarkably among the TF-induced and LPS-induced DIC models in rats, we recommend that TF-induced and LPS-induced DIC be approached as distinct models in order to determine the implications of their experimental and clinical use.
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PMID:Pathophysiology of disseminated intravascular coagulation (DIC) progresses at a different rate in tissue factor-induced and lipopolysaccharide-induced DIC models in rats. 1269 43

Tissue factor (TF) is an important regulator and effector molecule of coagulation in various inflammatory states. In sepsis, expression of TF by activated endothelial cells leads to disseminated intravascular coagulation. Scoparone is extracted from the traditional Chinese herb ARTEMISIA SCOPARIA and is known to have potent anti-inflammatory properties. In the current studies, we examined the effects of scoparone on inhibiting lipopolysaccharide (LPS)-induced TF expression in cultured human umbilical vein endothelial cells (HUVECs). Flow-cytometric analysis revealed LPS (10 micro g/ml)-activated surface TF induction was concentration-dependently inhibited by scoparone (10-400 micro M). The concentrations of scoparone used in this study did not affect cell viability. The elevation of the procoagulant activity of TF by LPS was suppressed by scoparone. The LPS-induced superoxide formation was markedly decreased by scoparone. Messenger RNA expression of TF in LPS-activated HUVECs was also reduced by scoparone. Furthermore, scoparone did not significantly affect the IkappaBalpha degradation. Our results demonstrate that the inhibition of scoparone on LPS-induced TF expression in HUVECs may mediate by the mechanisms suppressing superoxide anion formation and TF transcription.
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PMID:Scoparone inhibits tissue factor expression in lipopolysaccharide-activated human umbilical vein endothelial cells. 1292 92

Disseminated intravascular coagulation is a disorder that affects the function of the clotting system and is frequently associated with sepsis or septic shock. One of its leading symptoms is the decrease in circulating fibrinogen. We investigated the effect of fibrinogen concentrate (Haemocomplettan P) on fibrinogen plasma levels, coagulation parameters and mortality in a rat model of sepsis-induced disseminated intravascular coagulation. The disseminated intravascular coagulation was characterized by elevated thrombin-antithrombin complex and a sharp drop in circulating fibrinogen. Coagulation abnormalities were evaluated by thrombelastography. Plasma fibrinogen levels decreased from 2.06 +/- 0.2 to 0.16 +/- 0.1 g/l following administration of bacterial lipopolysaccharide. Thrombelastographic measurements revealed a concurrent decrease in maximum amplitude and an increase in reaction time. Treatment with fibrinogen concentrate (Haemocomplettan P, 25-200 mg/kg body weight intravenously) resulted in a statistically significant dose-dependent increase in fibrinogen plasma levels and amelioration of the measured coagulation abnormalities. Fibrinogen plasma concentrations were restored to normal levels when 200 mg/kg body weight fibrinogen concentrate was administered. A significant decrease in sepsis-induced mortality was observed in animals treated with Haemocomplettan P.
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PMID:The effect of fibrinogen concentrate administration on coagulation abnormalities in a rat sepsis model. 1516 42

Plasma D-dimer (DD) is considered to be one of the most useful markers in the diagnosis and assessment of disseminated intravascular coagulation (DIC). The present study was performed to clarify the role of DD in a rat model of lipopolysaccharide (LPS)-induced DIC in which low-molecular-weight heparin (LMWH) and tranexamic acid (TA) were used. We investigated whether a relationship exists between plasma DD levels and severity of DIC. Experimental DIC was induced in rats by a sustained 4-hour infusion of 30 mg/kg LPS administered via the tail vein (LPS group). Rats received either LPS alone (LPS group) or LPS combined with 200 U/kg LMWH (LPS+LMWH group) or 50 mg/kg TA (LPS+TA group) from -30 minutes to 4 hours. Blood was drawn from each rat at 4, 8, and 12 hours. Plasma levels of thrombin-antithrombin complex (TAT) and creatinine were suppressed in the LPS+LMWH group, and less glomerular fibrin deposition was observed compared with the LPS group. On the other hand, an increased level of creatinine and increased glomerular fibrin deposition were observed in the LPS+TA group compared with the LPS group. LMWH demonstrated a protective effect against LPS-induced DIC, resulting in increased survival at 12 hours, whereas TA had the opposite effect. From these results, it appears that LMWH protects against LPS-induced DIC, but TA exacerbates LPS-induced DIC. It was interesting that plasma levels of DD were almost completely suppressed by concurrent administration of either TA or LMWH in this LPS-induced DIC model. This finding suggested that plasma levels of DD were suppressed by inhibition of coagulation (reduced deposition of fibrin) in the LPS+LMWH group and that DD levels were also suppressed by inhibition of fibrinolysis (reduced degradation of fibrin by plasmin) in the LPS+TA group. Thus care should be taken when evaluating the significance of plasma DD levels, because suppressed levels can occur with progressive fibrin deposition and worsening organ dysfunction or improvement in the course of DIC.
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PMID:Significance of decreased plasma D-dimer levels following lipopolysaccharide-induced disseminated intravascular coagulation in rats. 1521 73

Gram-negative sepsis is associated with disseminated intravascular coagulation (DIC) due to endothelial damage, which is induced by inflammatory mediators released from phagocytes activated by lipopolysaccharide (LPS). DIC is a systemic hemorrhagic syndrome, which results from the consumption of coagulation factors for the formation of multiple thrombi in the systemic microvessels; it is associated with multiple organ failure. Therefore, not only the systemic activation of coagulation but also the inflammatory response has been perceived as the therapeutic target for DIC in sepsis. We gave attention that protein C inhibitor (PCI) acts as an inhibitor of both plasma kallikrein and thrombin, which are known to act not only as procoagulant proteases but also as chemotactic factors toward phagocytes. Then, we hypothesized that PCI possibly acts as an anti-DIC agent rather than an inhibitor of the protein C anticoagulant pathway under the pathophysiology of DIC, accompanied by the decrease in the thrombomodulin expression on endothelial cells. Our studies have suggested that PCI purified from human urine (uPCI) improves the pathophysiology of DIC through the inhibition of activities of plasma kallikrein and thrombin, and the activities of PCI are regulated by N-glycans. This review introduces the anti-DIC action of PCI and about the modification of N-glycosylation site(s) of PCI to heighten the value of PCI as an anti-DIC agent.
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PMID:Protein C inhibitor as an anti-disseminated intravascular coagulation agent--mechanism and modification. 1532 Aug 3

We investigated the relationship between endothelin, a potent vasoconstrictor peptide, and the pathophysiology of disseminated intravascular coagulation (DIC), using two models of DIC. Experimental DIC was induced by sustained infusion of 50 mg/kg lipopolysaccharide (LPS), or 3.75 U/kg thromboplastin, for 4 h via the rat tail vein. The effect of administration of a non-selective endothelin receptor antagonist (TAK-044) (2, 10, or 50 mg/kg, from -0.5 to 4 h) on thromboplastin-induced DIC was not significant. However, LPS-induced elevation of alanine aminotransferase, creatinine and glomerular fibrin deposition was significantly suppressed by co-administration of TAK-044 in a dose-dependent manner, although no effect of TAK-044 was observed on the platelet count, fibrinogen concentration or the level of thrombin-antithrombin complex. Moreover, plasma levels of D-dimer, which reflect the grade of fibrinolysis of cross-linked fibrin, were significantly increased by co-administration of each dose of TAK-044 in the LPS-induced DIC model in rats. Our results suggest that vasoconstriction, as well as depressed fibrinolysis, contribute to severe organ dysfunction in LPS-induced, but not thromboplastin-induced, DIC, and that endothelin plays a role in the development of organ injury in LPS-induced DIC in rats.
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PMID:Relationship between endothelin and the pathophysiology of tissue factor-induced and lipopolysaccharide-induced disseminated intravascular coagulation in rats: a study examining the effect of an endothelin receptor antagonist. 1538 27

Urinary trypsin inhibitor (UTI), a serine protease inhibitor, has been widely used as a drug for patients with acute inflammatory disorders such as disseminated intravascular coagulation, shock, and pancreatitis in Japan. Recent studies have demonstrated that serine protease inhibitors may play an anti-inflammatory role beyond merely an inhibitory action on neutrophil elastase at the site of inflammation at least in vitro. To clarify the direct contributions of UTI to inflammatory condition in vivo, we analyzed its roles in experimental systemic inflammatory response induced by intraperitoneal administration of lipopolysaccharide (LPS) using UTI deficient (-/-) mice and corresponding wild-type (WT) mice. After LPS (1 mg/kg) challenge, UTI (-/-) mice revealed a significant elevation of plasma fibrinogen and fibrinogen/fibrin degradation products and a decrease in white blood cell counts compared with WT mice. LPS treatment induced more severe neutrophilic inflammation in the lung and the kidney obtained from UTI (-/-) mice than in those from WT mice, which was confirmed by histological examination. The protein levels of proinflammatory mediators, such as macrophage chemoattractant protein (MCP)-1 in the lungs, MCP-1 and keratinocyte chemoattractant (KC) in the kidneys, and interleukin-1beta, macrophage inflammatory protein-2, MCP-1, and KC in the liver, were significantly greater in UTI (-/-) mice than in WT mice after LPS challenge. Our results suggest that UTI protects against systemic inflammatory response and subsequent organ injury induced by bacterial endotoxin, at least partly through the inhibition of the enhanced expression of proinflammatory cytokines and chemokines.
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PMID:Urinary trypsin inhibitor protects against systemic inflammation induced by lipopolysaccharide. 1557 31

Disseminated intravascular coagulation (DIC) is a pathological syndrome, which occurs following the uncontrolled widespread activation of blood coagulation, resulting in the intravascular formation of fibrin, which may lead to thrombotic occlusion of small and midsize vessels. The effects of 1-(alpha-naphthylmethyl)-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (YS-49, CAS 132836-42-1) and 1-(beta-naphthylmethyl)-6,7-dihydroxy-1,2,3,4-tetra-hydroisoquinoline (YS-51, CAS 213179-96-5) on the experimental DIC induced by lipopolysaccharide (LPS) in rats, were investigated. The oral administration of YS-49 and YS-51 (10 or 50 mg/kg) attenuated the dramatic increase of serum fibrinogen/fibrin degradation product (FDP) level, the decrease of plasma fibrinogen concentration and the number of platelets in blood and the prolongation of prothrombin time (PT) and activated partial thromboplastin time (aPTT) induced by LPS. The liver and kidney function parameters, aspartate amino-transferase (AST) and blood urea nitrogen (BUN), were also improved with YS-49 and YS-51. The above results suggest that YS-49 and YS-51 have therapeutic potential for DIC and/or accompanying multiple organ failure.
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PMID:Effects of two tetrahydroisoquinolines (YS-49 and YS-51) on experimental disseminated intravascular coagulation induced by lipopolysaccharide in rats. 1561 11

Urinary trypsin inhibitor (UTI), a serine protease inhibitor, has been widely used as a drug for patients with acute inflammatory disorders such as disseminated intravascular coagulation, shock, and pancreatitis. However, direct contribution of UTI to inflammatory diseases has not been established. The present study analyzed acute inflammatory lung injury induced by lipopolysaccharide (LPS) in UTI-deficient (-/-) mice and corresponding wild-type (WT) mice. UTI (-/-) and WT mice were treated intratracheally with vehicle or LPS (125 mug/kg). The cellular profile of bronchoalveolar lavage fluid, lung water content, histology, and expression of proinflammatory molecules in the lung were evaluated. After LPS challenge, both genotypes of mice revealed neutrophilic lung inflammation and pulmonary edema. UTI (-/-) mice, however, showed more prominent infiltration of inflammatory cells and edema than WT mice. After LPS challenge in both genotypes of mice, the lung levels of mRNA and/or protein expression of interleukin-1beta, macrophage inflammatory protein-1alpha, macrophage chemoattractant protein-1, keratinocyte chemoattractant, and intercellular adhesion molecule-1 (ICAM-1) were elevated in both groups, but to a greater extent in UTI (-/-) mice than in WT mice. These results suggest that UTI protects against acute lung injury induced by bacterial endotoxin, at least partly, through the inhibition of the enhanced local expression of proinflammatory cytokines, chemokines, and ICAM-1.
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PMID:Protective role of urinary trypsin inhibitor in acute lung injury induced by lipopolysaccharide. 1579 50

In a rat model of lipopolysaccharide (LPS)-induced disseminated intravascular coagulation (DIC), we used urokinase (UK) in an attempt to clarify the role of fibrinolysis and to investigate changes in plasma endothelin levels. Two kinds of experiment were performed. The first one: experimental DIC was induced by sustained infusion of 30 mg/kg LPS for 4 h via the tail vein, and two doses of UK (2.0 or 10.0 IU/g/4.5 h) were administered to rats 30 min before infusion of LPS, after which UK infusion was continued for a further 4 h. The second one: experimental DIC was induced by sustained infusion of 1 mg/kg/10 min LPS for 10 min, and two doses of UK (2.0 or 10.0 IU/g/4 h) were administered to rats at 30 min after LPS infusion. The parameters described below were determined at 4 h in the first experiment, at 4 h and 8 h in the second one. The similar results were observed in both kinds of experiment. There were no significant differences in plasma thrombin-antithrombin complex, fibrinogen or platelet number among the three DIC groups, in both kinds of experiment. Plasma levels of D-dimer were significantly increased in the LPS + higher dose of UK group when compared with the LPS group. The increased plasma plasminogen activator inhibitor (PAI) activity seen in the LPS group was significantly suppressed in the groups receiving UK (especially higher dose of UK). In addition, the increased plasma levels of creatinine and alanine aminotransferase seen in the LPS group were significantly suppressed in the groups receiving UK (especially higher dose of UK). Plasma levels of endothelin, known to be a potent vasoconstrictive agent, were markedly elevated by LPS infusion, and were significantly suppressed in the groups receiving UK of both kinds of experiment, in a dose-dependent fashion compared with LPS group. Glomerular fibrin deposition was significantly suppressed in the groups receiving UK when compared with the LPS group. No manifestations of bleeding were observed in any of the groups. Enhanced fibrinolysis and depressed endothelin induced by UK thus appear to play an important role in preventing the development of organ failure in the LPS-induced DIC model.
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PMID:Beneficial effects of urokinase on lipopolysaccharide-induced disseminated intravascular coagulation in rats: focus on organ function and endothelin levels. 1584 19


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