Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Plasma TNF-a and IL-6 levels of endotoxin-induced DIC in rabbits were measured by ELISA methods. Simultaneously, the effects of Reduqing (RDQ) on TNF-alpha and IL-6 were also studied. The results showed that TNF-alpha and IL-6 levels increased markedly in model group, which were confirmed with obvious damage of tissue or organ. Co-administration of RDQ could reduce plasma TNF-alpha and IL-6 levels, together with mild tissue or organ damage. These results indicated TNF-alpha and IL-6 might be involved in pathogenesis of endotoxin-induced DIC, RDQ might be used in preventing or treating DIC through mechanism of reducing TNF-alpha and IL-6 levels.
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PMID:[Effects of reducing injection on plasma TNF-alpha and IL-6 levels in rabbits with endotoxin-induced DIC]. 754 88

The blood coagulation and fibrinolysis of 33 patients with compensated liver cirrhosis and 31 patients with hepatocellular carcinoma were examined using several markers, namely thrombin-antithrombin III complex (TAT), plasmin-alpha 2 plasmin inhibitor complex (PIC), antithrombin-III (AT-III) and prothrombin time, and the relationship between these markers, endotoxemia, and TNF-alpha was examined. These patients had no complications due to hepatic failure, such as infections, encephalopathy, ascites, G-I bleeding and clinical DIC. PIC was not elevated, but TAT tended to be elevated in LC and significantly elevated in HCC. AT-III was decreased in LC and HCC, and the blood endotoxin was partly positive in LC and HCC, but was not correlated with AT-III or PT. The TAT level in the blood-endotoxin-positive patients measured by endospecy methods was higher than that in the negative patients, and was significantly correlated with the blood endotoxin level in the LC and HCC patients (r = 0.57, r = 0.88, p < 0.01). No relationship was observed between TNF-alpha and blood endotoxin. In conclusion, (1) blood coagulability was activated already in compensated LC and HCC, but was not connected with fibrinolysis, (2) the activation of coagulability was closely related with endotoxemia, and (3) TNF-alpha was not correlated with blood endotoxin or TAT.
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PMID:[Blood coagulation and fibrinolysis in relation to endotoxemia in liver cirrhosis and hepatocellular carcinoma]. 756 21

TNF-alpha induces changes in endothelial cell functions, such as upregulation of tissue factor, resulting in endothelial procoagulant activity which may play a role in disseminated intravascular coagulation. The procoagulant activity of TNF-alpha-stimulated endothelial cell monolayers was studied in a human ex vivo native (nonanticoagulated) blood flow system using the three thrombin inhibitors recombinant hirudin, Ro 46-6240, and heparin. Under venous blood flow conditions (shear rate 65 s-1) recombinant hirudin, Ro 46-6240, and heparin inhibited fibrin deposition on the endothelial cells by 50% at concentrations of 14, 28, and 412 ng/ml, respectively. The highest tested concentrations of the thrombin inhibitors reduced the postchamber fibrinopeptide A levels from 713 +/- 69 to < 70 ng/ml. Surprisingly, even at relatively high inhibitor concentrations, some local fibrin deposits were found on TNF-alpha-stimulated cells, suggesting that some endothelial cells possess higher procoagulant activity than others. Therefore, the surface expression pattern of tissue factor, the primary initiator of coagulation in this system, was examined by immunogold-silver staining. The results showed that the tissue factor density on the cell surface varied strongly among TNF-alpha-stimulated endothelial cells. Using TNF receptor-selective agonistic mutants of TNF-alpha, it was demonstrated further that the heterogenous surface expression of tissue factor was mediated entirely by the 55-kD TNF receptor and did not involve the 75-kD TNF receptor. We conclude that in this system TNF-alpha induces heterogenous tissue factor expression which may lead to a high local thrombin concentration, such that even in the presence of thrombin inhibitors focal fibrin deposition occurs.
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PMID:Endothelial cells stimulated with tumor necrosis factor-alpha express varying amounts of tissue factor resulting in inhomogenous fibrin deposition in a native blood flow system. Effects of thrombin inhibitors. 818 39

The procoagulant activity of mononuclear cells (MNCs) may play an important role in the disseminated intravascular coagulation seen in septic shock. This study compares the capacity of Escherichia coli (E. coli) and recombinant human TNF-alpha (rhTNF-alpha) to induce procoagulant activity by baboon MNCs. In vivo studies showed that MNC procoagulant activity was significantly increased at T + 120 min after LD100 E. coli infusion into baboons. Most of this procoagulant activity was attributable to tissue factor. In contrast, a bolus infusion of rhTNF-alpha (150 micrograms/kg) and a monoclonal antibody to activated protein C (2 mg/kg) did not induce any increase of MNC procoagulant activity at T + 120 min even though the plasma TNF-alpha level was 10 times higher than that seen following infusion of E. coli. In vitro studies showed that E. coli at concentrations comparable to that observed in the vivo study and LPS at a concentration of 2.5 ng/mL induced more intense tissue factor expression by both human and baboon monocytes than rhTNF-alpha in the concentrations ranging from 10 to 1,000 ng/mL. These results suggest that TNF-alpha alone is not sufficient to induced noticeable MNC procoagulant activity, at least, in the early stage of this septic shock model.
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PMID:Comparison of the capacity of rhTNF-alpha and Escherichia coli to induce procoagulant activity by baboon mononuclear cells in vivo and in vitro. 872 87

Adult respiratory distress syndrome and disseminated intravascular coagulation are important pathologic conditions affecting the outcome of patients with sepsis. To elucidate the possible therapeutic efficacy of SM-12502, a novel platelet activating factor antagonist, on acute lung injury and disseminated intravascular coagulation in sepsis, we investigated the effect of SM-12502 on an endotoxin (ET)-induced septic model in rats. SM-12502 prevented ET-induced increases in pulmonary vascular permeability and ET-induced histologic changes, such as leukocyte infiltration and pulmonary interstitial edema, 6 h following the administration of ET (5 mg/kg). SM-12502 also inhibited the decrease in fibrinogen and the increase in fibrin and fibrinogen degradation products observed following ET administration. SM-12502 prevented increases in the serum concentration of tumor necrosis factor (TNF) 90 min following ET administration in vivo, and significantly inhibited the production of TNF-alpha by ET-stimulated monocytes in vitro. These findings suggest that SM-12502 attenuates the actions of endotoxin by the inhibition of TNF production.
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PMID:A novel platelet activating factor antagonist, SM-12502, attenuates endotoxin-induced disseminated intravascular coagulation and acute pulmonary vascular injury by inhibiting TNF production in rats. 882 94

The pathogenesis of disseminated intravascular coagulation (DIC) has, in part, been attributed to the impairment of the natural anticoagulant protein C/protein S pathway. DIC, which frequently occurs during sepsis, has been linked to cytokines that can induce or modulate procoagulant activity. Three of these cytokines, IL-1 alpha, IL-6, and TNF-alpha have been reported to be increased in the early stages of sepsis. In the present study, we have stimulated HepG-2 hepatoma cell cultures with recombinant human IL-1 alpha, IL-6, TNF-alpha, and oncostatin M (OSM). The results demonstrated that TNF-alpha, and to a lesser degree, IL-1 alpha, could significantly suppress IL-6 upregulation of protein S, whereas the effects of OSM was only suppressed by the combination of IL-1 alpha and TNF-alpha. The combination of IL-1 alpha and TNF-alpha also suppressed protein S production below that of control or basal levels. These results indicate that IL-1 alpha and TNF-alpha may play important regulatory roles in coagulation.
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PMID:TNF-alpha suppresses IL-6 upregulation of protein S in HepG-2 hepatoma cells. 892 89

The effect of activated platelets on cytokine production by human peripheral blood mononuclear cells (PBMC) was investigated. When PBMC were coincubated with activated autologous platelets amid lipopolysaccharide (LPS, 50-100 pg/mL) for 8 h, the production of interleukin (IL)-1alpha increased 11- to 18-fold and tumor necrosis factor (TNF)-alpha 3- to 5-fold compared with PBMC without platelets. Activated platelets in a dual-chamber well that prevented platelet-PBMC contact but permitted passage of soluble factors enhanced IL-1alpha production (P < .01). Platelet-PBMC contact in the chamber resulted in a further enhancement of IL-1alpha production. These data suggest that platelet-PBMC interaction, both directly and with platelet-derived factors, enhances production of shock-producing IL-1alpha and TNF-alpha, albeit differently. The interaction of platelets with monocytes may play an important role in the pathophysiology of sepsis and disseminated intravascular coagulation.
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PMID:Interaction with autologous platelets multiplies interleukin-1 and tumor necrosis factor production in mononuclear cells. 898 5

Tumor necrosis factor (TNF)-alpha and platelet-activating factor (PAF) are important mediators of inflammatory reactions, and their release is controlled by a positive feedback network. However, the regulatory mechanisms underlying the interaction of these two molecules are unknown. Within 10 min of the injection of lipopolysaccharide (LPS) into C57BL/6 mice, effects inducible by PAF such as anaphylactic shock-like symptoms, disseminated intravascular coagulation, and hemorrhage in renal medullae were observed, and all these pathological changes were prevented by the PAF antagonist, BN 50739. The plasma level of PAF after LPS injection reached a peak at 5 min. TNF-alpha gene expression was evident 20 min after LPS injection and was maximal at 40 min, and the level of serum TNF-alpha reached a peak at 1 h. Pretreatment with BN 50739 inhibited LPS-induced TNF-alpha gene expression and protein synthesis in a dose-dependent manner. Injection of PAF or treatment of the macrophage cell line, J774A.1, with PAF activated the transcription factor, nuclear factor (NF)-kappa B, which is essential for inducible TNF-alpha transcription. The activation of NF-kappa B by PAF preceded the LPS-mediated TNF-alpha gene expression. Pretreatment with BN 50739 inhibited LPS-induced mobilization of NF-kappa B in a dose-dependent manner in vivo as well as in vitro. These data suggest that PAF, which is released immediately or shortly after LPS injection, induces the expression of TNF-alpha through the activation of NF-kappa B.
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PMID:Involvement of nuclear factor-kappa B in platelet-activating factor-mediated tumor necrosis factor-alpha expression. 939 2

Systemic inflammatory response syndrome(SIRS) is a pathologic condition associated with infection and tissue injury and it frequently leads to multiple organ dysfunction syndrome and disseminated intravascular coagulation(DIC). Pathologic events observed in SIRS can be attributable to the actions of cytokines such as tumor necrosis factor-alpha(TNF-alpha) and interleukin-1 beta. These cytokines activate monocytes and endothelial cells to induce the expression of tissue factor on their cell surfaces. Tissue factor then activates the extrinsic pathway of the coagulation system to induce microthrombus formation. These cytokines also contribute to microthrombus formation by decreasing the endothelial expression of thrombomodulin and glycosaminoglycans that regulate the coagulation system. Consequently, these cytokines induce DIC. These cytokines can activate neutrophils to release various inflammatory mediators which are capable of damaging the endothelial cell. The resultant endothelial cell injury, together with the microthrombus formation, may lead to microcirculatory disturbance which plays a role in ischemic organ dysfunction. Although physiological anticoagulants such as antithrombin and activated protein C can prevent endothelial cell injury by inhibiting leukocyte activation, heparin does not. Thus, these anticoagulants except for heparin may be effective in treating DIC associated with SIRS.
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PMID:[SIRS and the coagulation of normality]. 1089 68

Although it has been suggested that some biological activities of platelet-activating factor (PAF) are mediated by, at least in part, reactive oxygen intermediates (ROI), the precise mechanisms underlying the interaction between the two remains to be elucidated. Antioxidants, such as alpha-tocopherol acid succinate, N-acetyl-L-Cysteine, pyrrolidinedithiocarbamate failed to inhibit PAF-induced immediate systemic reactions such as lethality, symptoms of disseminated intravascular coagulation, and histological changes such as pulmonary edema and hemorrhage in renal medullae 10 min following PAF injection. In contrast. antioxidants significantly inhibited both the in vivo and in vitro PAF-induced NF-kappaB activation and NF-kappaB-dependent TNF-alpha expression. The effects of the antioxidants were due to their inhibition of PAF-induced degradation of IkappaBalpha, a protein responsible for keeping NF-kappaB in an inactive form. A protein tyrosine kinase and N-tosyl-L-phenylalanine chloromethyl ketone sensitive serine protease were involved in both PAF- and H2O2-induced NF-kappaB activation. Collectively, these data indicate that the PAF-induced NF-kappaB activation is selectively mediated through the generation of ROI.
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PMID:Selective involvement of reactive oxygen intermediates in platelet-activating factor-mediated activation of NF-kappaB. 1092 4


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