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)

Endotoxic lipopolysaccharide (LPS) is a proinflammatory agonist produced by gram-negative bacteria and a contributor to the majority of the 400,000 septic shock cases recorded annually in US hospitals. The primary target cells for LPS are monocytes and macrophages. Their response consists of massive production of proinflammatory cytokines, reactive oxygen- and nitrogen-intermediates, procoagulants, and cell adhesion molecules. In turn, expression of these LPS-responsive factors contributes to collapse of the circulatory system, to disseminated intravascular coagulation, and to a 30% mortality rate. A common intracellular mechanism responsible for the expression of septic shock genes in monocytes and macrophages involves the activation of NF-kappaB. This transcription factor is regulated by a family of structurally related inhibitors including IkappaBalpha, IkappaBbeta, and IkappaBepsilon, which trap NF-kappaB in the cytoplasm. In this report, the investigators show that LPS derived from different gram-negative bacteria activates cytokine-responsive IkappaB kinases containing catalytic subunits termed IKKalpha (IKK1) and IKKbeta (IKK2). The kinetics of IKKalpha and IKKbeta activation in LPS-stimulated human monocytic cells differ from that recorded on their stimulation with tumor necrosis factor-alpha, thereby implying a distinct activation mechanism. LPS-activated IKK complexes phosphorylate all 3 inhibitors of NF-kappaB: IkappaBalpha, IkappaBbeta, and IkappaBepsilon. Moreover, LPS activates IKKbeta preferentially, relative to IKKalpha. Thus, IKK complex constitutes the main intracellular target for LPS-induced NF-kappaB signaling to the nucleus in human monocytic cells to activate genes responsible for septic shock.
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PMID:IkappaB kinase complex is an intracellular target for endotoxic lipopolysaccharide in human monocytic cells. 1047 96

Although morbidity following cryotherapy is usually minor, a syndrome of multiorgan failure and disseminated intravascular coagulation (DIC) has been described and referred to as the cryoshock phenomenon. We hypothesized that mediators similar to those in septic shock may be involved in this syndrome. In this study we aimed to assess the plasma concentrations of the cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) following hepatic cryotherapy and to relate them to the duration and volume of freezing and to hepatocellular injury. Between April and December 1997 blood samples were taken preoperatively and at different times postoperatively from patients undergoing hepatic artery catheter-insertion (HAC) (n = 15), cryotherapy (n = 5), liver resection (n = 9), liver resection and edge cryotherapy (n = 7), or liver resection and cryotherapy of additional lesions (n = 9). They were analyzed for serum aspartate transaminase (AST) and plasma TNF-alpha and IL-6 levels. There was a significant association (Pearson correlation) of serum AST levels 1 hour postoperatively with plasma TNF-alpha and IL-6 levels at the end of the procedure. In patients undergoing cryotherapy or resection with cryotherapy of additional lesions (n = 14), the volume and duration of hepatic freezing were significantly associated with postoperative serum AST and plasma TNF-alpha and IL-6 levels at various postoperative times. Hepatic cryotherapy is followed by cytokine release, with postoperative plasma TNF-alpha and IL-6 levels associated with the degree of hepatic cryotrauma. These mediators may be involved in the occurrence of cryoshock following large-volume hepatic freezing.
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PMID:Interleukin-6 and tumor necrosis factor-alpha levels following hepatic cryotherapy: association with volume and duration of freezing. 1051 41

We investigated the significance of platelet activation and platelet-derived microparticles (PMP) in 14 patients with systemic inflammatory response syndrome (SIRS) and hematological malignancies. In the phenotypic analysis of lymphocytes, there was a significant decrease of total and activated T cells after panipenem/betamipron (PAPM/BP) treatment (p<0.05). The percentages of helper/inducer T cells and suppressor/cytotoxic T cells were insignificantly decreased after PAPM/BP treatment. The number of natural killer (NK) cells of potent activity was significantly decreased after treatment (p<0.05). The levels of the cytokines interleukin (IL)-1beta, IL-6, and IL-8 in the patients were increased before treatment. IL-1beta concentrations were not changed after treatment. In contrast, the IL-6 and IL-8 levels were significantly decreased (p<0.05) after treatment, while tumor necrosis factor (TNF)-alpha and interferon gamma remained almost normal. We found an increase of soluble IL-2 receptor (sIL-2R) and soluble vascular cell adhesion molecule-1 (sVCAM-1) levels in the patients before treatment. After treatment, the sIL-2R concentrations tended to be decreased and sVCAM-1 levels showed a significant decrease (p<0.01). In contrast, soluble thrombomodulin (sTM) level did not change. Regarding the platelet activation markers, CD62P, CD63, and PMP levels in the patients were increased before treatment. CD62P and CD63 tended to be decreased after treatment, whereas PMP levels were significantly reduced from 1,056+/-103 to 762+/-64/10(4) platelets (p<0.05). Furthermore, CD62P, CD63, and PMP correlated with the levels of IL-6 and IL-8. These results suggest that activated platelets and PMP may be predictive markers in pre-disseminated intravascular coagulation and hypercytokine conditions related to SIRS.
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PMID:Relationship between platelet activation and cytokines in systemic inflammatory response syndrome patients with hematological malignancies. 1051 85

A 32-year-old woman in the 16th week of pregnancy was admitted to our hospital because of high fever. Laboratory findings disclosed pancytopenia and extremely elevated serum LDH and ferritin levels. Coagulation tests showed disseminated intravascular coagulation. Serum soluble interleukin-2 receptor, tumor necrosis factor-alpha, and interleukin-6 levels were high, but serum interferon-gamma was below the detectable limit. Reactive Epstein-Barr virus (EBV) infection was diagnosed on the basis of a high titer of IgG antibodies to the EBV capsid antigen and early antigen. EBV was demonstrated in the peripheral blood and bone marrow cells by polymerase chain reaction. Mature histiocytosis and hemophagocytosis were detected in the bone marrow. A diagnosis of EBV-associated hemophagocytic syndrome (EBV-AHS) was made. Neither prednisolone (PSL 30 mg/day, P.O.) nor methylprednisolone (m-PSL) pulse therapy (1,000 mg/day for 3 days) induced a response. Thereafter, treatment with m-PSL pulse therapy (1,000 mg/day for 3 days) and i.v. administrations of high-dose immunoglobulin (20 g/day for 3 days) in combination with acyclovir (750 mg/day) and gabexate mesilate (2 g/day) induced remission of the disease. Maintenance therapy consisted of PSL (5 mg/day, P.O.) and camostat mesilate (600 mg/day, P.O.). The patient delivered a healthy male infant in the 35th week of pregnancy via natural birth. Reports of pregnant women with EBV-AHS are rare, and the choice of therapy has not yet been established. The present case study suggested the above combination treatment is useful and safe, and capable of changing the fulminant course of EBV-AHS during pregnancy without the use of anticancer drugs.
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PMID:[Epstein-Barr virus-associated hemophagocytic syndrome during mid-term pregnancy successfully treated with combined methylprednisolone and intravenous immunoglobulin]. 1065 79

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

Disseminated intravascular coagulation (DIC) is an acquired syndrome characterized by intravascular fibrin formation occurring in the course of a variety of severe diseases. In gram-negative sepsis, endotoxin is the bacterial component eliciting a cascade of tissue factor dependent hypercoagulable reactions mediated by cytokines, including tumor necrosis factor-alpha and interleukin-6. Fibrinolysis is activated in this process by the action of tumor necrosis factor-alpha, but its activity is impaired by the predominant inhibitory effect of plasminogen activator inhibitor-1. Natural inhibitory mechanisms include antithrombin, the protein C system, and tissue factor pathway inhibitor. Each of these defense systems counteracts the harmful effects of DIC, and its acquired deficiency is associated with increased mortality in observational studies. The generation of several proteases in DIC, including factor Xa and thrombin, has potential interactions with inflammatory pathways that may potentiate the systemic inflammatory syndrome that often accompanies DIC. Experimental studies support the notion that defects in the protein C pathway modulate the inflammatory response, and illustrate that coagulation and inflammation are coupled systems in DIC.
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PMID:Pathophysiology of disseminated intravascular coagulation in sepsis. 1100 90

Extracorporeal detoxification has been proposed to treat patients with hepatic encephalopathy (HE) not responding to standard therapy. To investigate the biocompatibility of a cuprophane charcoal-based detoxification device, a prospective, randomized, controlled study was performed. Of 41 consecutive patients with cirrhosis and HE grade II or III who did not improve with conventional treatment, 20 patients (median age, 56 years; range, 33 to 71 years; 13 men) were randomly assigned to either ongoing conventional treatment or one additional 6-hour treatment with a sorbent suspension dialysis system. Main outcome parameters were physiological function and blood parameters of biocompatibility. In the 10 patients undergoing combined conventional and sorbent suspension dialysis treatment, blood pressure remained unchanged and body temperature and heart rate increased (P: < 0.01). Platelet count decreased (medians, from 75 to 26 g/L; P: < 0.001) and international normalized ratio increased after combined treatment (2.0 to 2.2; P: < 0.001). Three patients developed bleeding complications during treatment or shortly after. Treated patients showed increases in levels of plasma elastase (104 to 586 microg/L; P: = 0.001), tumor necrosis factor-alpha (5.4 to 7.5 pg/mL; P: = 0.04), and interleukin-6 (118 to 139 pg/mL; P: = 0.04), but not interferon-gamma and E-selectin. No changes were observed in the 10 patients treated conventionally. In conclusion, despite technical refinements compared with charcoal hemoperfusion, biocompatibility of sorbent suspension dialysis is still very limited. Clinical complications were apparently caused by blood-membrane interactions and disseminated intravascular coagulation. We suggest further developments in design and appropriate strategies of anticoagulation to improve the biocompatibility of artificial liver support.
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PMID:Biocompatibility of a cuprophane charcoal-based detoxification device in cirrhotic patients with hepatic encephalopathy. 1109 44

It is increasingly apparent that there is a bidirectional interaction between the maternal immune system and the reproductive system during pregnancy. Pregnancy is associated with a suppression of maternal specific immune responses, which process underlies the protection of fetal tissues expressing paternally inherited alloantigens. However, recent evidence indicates that the suppression of specific, lymphocyte-mediated immune responses during pregnancy is accompanied by activation of the non-specific arm of the maternal immune response. In the present study, we have investigated the effect of pregnancy on the non-specific immune response induced by bacterial lipopolysaccharide (LPS, endotoxin) in mice. Pregnancy enhanced the LPS-induced production of proinflammatory cytokines, including tumor necrosis factor-alpha, interleukin (IL)-6, and interferon-gamma. On the other hand, LPS-induced levels of the anti-inflammatory cytokine IL-10 were suppressed in pregnant mice. These alterations in cytokine production correlated with an increased susceptibility for endotoxemic mortality in the pregnant mice. Although adrenergic receptors are important regulators of cytokine production in non-pregnant mice, the alpha(2)- and the beta-adrenoceptor-mediated modulation of cytokine production ceases to operate during pregnancy associated with severe endotoxemia. These data may explain how excessive activation of the non-specific immune responses during pregnancy can contribute to the increased severity of some maternal diseases, including septic shock, and can be an important pathophysiological factor in disseminated intravascular coagulation or preeclampsia.
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PMID:Enhanced tumor necrosis factor-alpha-specific and decreased interleukin-10-specific immune responses to LPS during the third trimester of pregnancy in mice. 1169 56

In the course of sepsis, severe coagulopathy and disseminated intravascular coagulation (DIC) are common events. Therefore, substances known to interfere with the coagulation cascade have been studied in animal models of sepsis. Among them, antithrombin III (AT III) was reported to be a promising therapeutic tool because it exhibited anti-inflammatory properties in addition to its anticoagulative effects. In our studies using vascular smooth muscle cells (VSMC) as a monoculture model, contradictory effects of AT III on the release of the proinflammatory agonists tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) were found. Whereas AT III inhibited the lipopolysaccharide (LPS)-induced production of these cytokines on both the transcriptional and the translational levels when given at higher concentrations (5 or 10 U/ml), lower amounts of AT III did not show this suppressive effect. In contrast, 0.5, 1, and 5 U/ml AT III led to an enhancement of TNF-alpha synthesis when combined with LPS. To date, we cannot provide a mechanism to explain the AT III-promoted modulation of TNF-alpha and IL-1beta generation in VSMC. However, with respect to its potential therapeutic benefit in systemic inflammatory conditions, AT III should not be regarded strictly as an anti-inflammatory modulator.
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PMID:Effects of antithrombin III on tumor necrosis factor-alpha and interleukin-1beta synthesis in vascular smooth muscle cells. 1179 64

Severe consumption coagulopathy has been detected in rats after Lopap (a prothrombin activator from Lonomia obliqua caterpillar bristles) infusion and in humans after accidental contact with L. obliqua bristles. However, platelet count and antithrombin (AT) levels were only modestly affected, suggesting that a different form of blood coagulation activation may be involved in this hemorrhagic syndrome. Here we describe that Lopap had no effect on aggregation of washed human platelets induced by several agonists, suggesting that it might not impair platelet function in vivo. AT was able to inhibit the amidolytic activity of thrombin generated by incubation of Lopap with prothrombin in a purified system, which may be different from that generated by the prothrombinase complex in vivo. The surface expression of both ICAM-1 and E-selectin but not of VCAM-1 was upregulated by Lopap in cultured HUVEC, suggesting that it may behave differently from other mediators, such as thrombin and tumor necrosis factor-alpha.
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PMID:Effects of lopap on human endothelial cells and platelets. 1191 Jan 93


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