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

Employing the test model which we developed for the investigation of platelet adhesiveness and aggregation in vivo, experiments demonstrated that the sulfonyl urea derivatives, glibenclamide, gliclazide, and HB 180, as well as the carboxylic acid derivative, meglitinide, are able to inhibit, in a dose-dependent relationship, the adherence of i.v. injected Walker-256-carcinosarcoma cells to the vascular endothelium of the rat mesentery, as well as to reduce significantly the rate of instantly occurring terminal tumor cell embolism of the lung. Since venous blood platelet count in surviving animals is inversely proportional to the number of the tumor cells which adhere to the vascular endothelium, one can deduce that tumor cell embolism is an immediate result of a massively occurring disseminated intravascular coagulation (DIC) which may be induced by i.v. injection of thromboplastic active carcinosarcoma cells and leads primarily to a drastic platelet count reduction. All four substances inhibit this platelet count reduction as well as the directly correlated tumor cell embolism mortality rate in a linear dose-dependent fashion. Their action can therefore be explained as being mediated via an inhibition of platelet adhesion and aggregation to the circulating tumor cells. Our proof of platelet aggregation in vivo correlates with the results obtained by Klaff et al. (1979), as far as a normalization of the pathologically increased platelet aggregation tendency in vitro in diabetics following 4-6 weeks of therapy with the sulfonyl urea derivatives glibenclamide and gliclazide.
 ...
PMID:The inhibition of cancer cell stickiness, a model for investigation of platelet aggregation inhibitors in vivo. Effect of the sulfonyl urea derivatives, glibenclamide, gliclazide, and HB180, as well as the carboxylic acid derivative, meglitinide. 680 52

The interaction of immunocompetent cells with the vascular endothelium is of prime importance for the development of septic multiple organ failure. There is evidence from in-vitro studies that the methylxanthine derivative pentoxifylline can attenuate the extent of inflammatory reactions by amplification of cell-derived endogenous regulators. For instance, pentoxifylline potentiates the anti-inflammatory actions of adenosine, prostacyclin, and prostaglandins of the E series by its synergistic action on intracellular cyclic AMP. By this mechanism, pentoxifylline inhibits the oxygen-radical production of polymorphonuclear leukocytes, the aggregation of platelets, disseminated intravascular coagulation, and the production of cytokines. Consequently, pentoxifylline improves perfusion in the microcirculation as well as tissue oxygenation. Further studies will clarify whether the promising results obtained with pentoxifylline in experimental septic shock will be confirmed under clinical conditions.
 ...
PMID:[Drug therapy of sepsis. An indication for pentoxifylline?]. 817 75

Induction of tissue factor (TF) expression on monocytes and endothelial cells is central to the development of septic coagulopathy. Serum concentrations of endotoxin in septic patients who develop disseminated intravascular coagulation (DIC) do not, however, reach the levels that would directly stimulate TF expression on either monocytes or endothelium. We show, using an in vitro coculture system, that the interaction of monocytes with endothelium induces the expression of significant levels of TF. Unstimulated cocultures of monocytes (2 x 10(4)/well) and endothelial cells (2 x 10(4)/well) produced 35.3 +/- 8.5 mU of PCA/well, representing a 5-fold increase over the combined PCA of each cell type cultured alone (7.1 +/- 1.5 mU, n = 6, P < 0.001). Significant enhancement was also found in the presence of low concentrations of LPS. Induction of TF protein was confirmed by Western blotting. Fixation of monocytes with paraformaldehyde completely abolished TF induction in cocultures, whereas fixation of endothelium had no effect, suggesting that TF induction occurred in monocytes rather than endothelial cells. Induction of TF in cocultures could be further augmented by preincubating the endothelial cells with IFN-gamma. When endothelium was prestimulated with 500 U/ml IFN-gamma there was 142 +/- 11% increase over unstimulated cocultures (n = 5, P < 0.01). TF induction was inhibited by 32 +/- 6% in the presence of anti-ICAM-1 mAb (n = 5, P < 0.01). Our results suggest that monocyte interactions with vascular endothelium, regulated by inflammatory cytokines, and mediated by adhesive ligand binding, leads to the induction of functional monocyte TF protein, which may be responsible for the initiation of DIC in sepsis.
 ...
PMID:Induction of tissue factor expression in human monocyte/endothelium cocultures. 854 49

Lung fragments from 12 patients were collected immediately after death and studied by light and electron microscopy and by immunohistochemistry to describe the main morphologic and ultrastructural aspects of the lung and platelets in leptospirosis (Weil's syndrome), to search for the possibility of disseminated intravascular coagulation (DIC), and to assess the relationship between endothelial lesions and local platelet aggregation and the leptospiral antigen distribution, as well as its relationship with the intensity of the lesions. The immunohistochemical results for fibrin aggregates were positive in the lumen and/or on the vascular endothelium in nine cases and on the alveolar surface in seven cases, leading to the diagnosis of the adult respiratory distress syndrome in these seven cases. Test results for leptospiral antigen by immunohistochemistry were positive in eight cases with no direct relationship between antigen deposits in the pulmonary vascular endothelium and intensity of the lesions. The ultrastructural findings were uniform and constant. Capillary lesions were characterized by swelling of endothelial cells, an increase in pinocytotic vesicles, and giant dense bodies in the cytoplasm of these cells. No necrosis, rupture, nor exposed subendothelial collagen was observed outside the hemorrhagic areas, and the intercellular junctions were preserved. The lung involvement in severe human leptospirosis presents as hemorrhagic pneumopathy with septal capillary lesions that are the usual cause of death. The thrombocytopenia that was verified in 11 of 12 patients in our study seems to bear no relationship to DIC and seems to be determined by activation, adhesion, and aggregation of platelets to the stimulated vascular endothelium, with an amorphous electron-dense substance between the endothelial cells and the adherent platelets in places where the subendothelial collagen was not exposed.
 ...
PMID:Lung lesions in human leptospirosis: microscopic, immunohistochemical, and ultrastructural features related to thrombocytopenia. 908 Aug 78

We examined hemostatic molecular markers in various thrombotic disorders. The efficacy of treatment in relation to the disseminated intravascular coagulation (DIC) score when the treatment was begun showed that greater efficacy was achieved in Pre-DIC than in DIC patients. The outcome was poorer with increasing DIC score, suggesting that early treatment is important. The sensitivity in some of molecular markers was high for both DIC and Pre-DIC. Receiver operating characteristic analysis suggest that soluble fibrin monomer level could be the most useful marker for the diagnosis of DIC. In examination of these markers in deep vein thrombosis, pulmonary embolism, acute myocardial infarction, and cerebral infarction, plasminogen activator inhibitor-1 and activated protein C-protein C inhibitor complex were useful marker for the diagnosis. Increased plasma GMP-140 was suggested to be the activation of platelets. The patients with high levels of plasma thrombomodulin (TM) considered to be a marker of vascular endothelial injuries became poor outcome. We will term these patients with high TM as systemic vascular endothelium injuries syndrome, and treat those by protecting the vascular endothelium.
 ...
PMID:[Study of hemostatic molecular marker]. 913 93

Activated leukocytes are thought to contribute to respiratory dysfunction, alterations in microvascular permeability, disseminated intravascular coagulation, and thrombosis, all of which can complicate cardiopulmonary bypass (CPB). We have measured the levels of circulating proinflammatory cytokines (IL-6, 8), polymorphonuclear leukocytes elastase (PMNL-E), and vascular endthelial factors (ET-1, TM, sICAM-1) in patients undergoing open heart surgery with CPB. Patients were divided into a control group and a ulinastatin group. We have examined the effects of ulinastatin on these humoral mediators and postoperative pulmonary function. Every factor except IL-8 increased after CBP in control group. IL-6 and PMNL-E declined sharply to normal level in a few hours, but it took several days after surgery for ET-1, TM, and sICAM-1 to return to preoperative levels. Ulinastatin significantly suppressed the elevation of PMNL-E after CPB, indirectly suppressing the increase of other factors. There was no significant relationship between levels of humoral mediators and postoperative pulmonary function between the two groups. Our results suggest that ulinastatin alleviates the damage of vascular endothelium due to CPB (first attack), and this may be beneficial to reduce excessive inflammatory reaction against secondary insults.
 ...
PMID:[Effects of ulinastatin on PMNL and vascular endothelial injury in patients undergoing open heart surgery with CPB]. 949 95

Reactive oxygen species (ROS) are constantly produced in human beings under normal circumstances. Antioxidant systems help defend the body against ROS but may be overwhelmed during periods of oxidative stress, which can cause lipid peroxidation, damage to DNA, and cell death. Critical illness, such as sepsis or adult respiratory distress syndrome, can drastically increase the production of ROS and lead to oxidative stress. Sources of oxidative stress during critical illness include activation of the phagocytic cells of the immune system (the respiratory burst), the production of nitric oxide by the vascular endothelium, the release of iron and copper ions and metalloproteins, and the vascular damage caused by ischemia reperfusion. Only indirect measurements of ROS are available, but the presence of oxidative stress in critical illness is supported by clinical studies. In general, serum antioxidant vitamin concentrations seem to decrease and measures of oxidative stress seem to increase in critically ill populations. Oxidative stress has been associated with sepsis, shock, a need for mechanical ventilation, organ dysfunction, acute respiratory distress syndrome, disseminated intravascular coagulation, surgery, and the presence of an acute-phase response. In addition, higher levels of oxidative stress seem to occur in patients with more notable injuries. Dietary supplementation with antioxidant vitamins seems to be the logical answer to decreasing serum antioxidant concentrations, but antioxidants may have adverse effects. The benefit of supplementing antioxidants in critically ill populations has not been shown and requires further study.
 ...
PMID:Oxidative stress in critical care: is antioxidant supplementation beneficial? 973

Increased fibrinolytic activity and consumption coagulopathy are common consequences of liver transplantation and are a major cause of morbidity and death. In the present investigation the effects of hepatic ischemia on the coagulation mechanism were studied in the stump-tail monkey. The results suggest that, although fibrinolytic activity is induced by both major intraabdominal operations as well as one hour of hepatic ischemia, consumption coagulopathy, presumably due to intravascular clotting, is enhanced by the revascularization of the ischemic liver, possibly because of clotting within the liver itself. Release of a plasminogen activator from the liver due to hepatic ischemia alone is not demonstrated by these studies. It is believed that the first phase of intravascular coagulation after liver transplantation is due to release of tissue activators from vascular endothelium, which may be minimized by the action of ganglionic blocking agents. The severity of fibrinolysis in this stage is aggravated by the "liverless state," in which no clearance of plasminogen activators occurs. The degree of liver injury directly affects the ability of the liver to control hypercoagulability in the second phase. Thrombus formation which we believe occurs during this phase may be minimized by use of continuous controlled heparinization.
 ...
PMID:Effects of hepatic ischemia on coagulation in primates. Application to liver transplantation. 1048 79

The ability to transplant pig organs into humans would resolve the current crisis in the supply of cadaveric human organs for the treatment of end stage disease. Several immunologic barriers need to be overcome if pig-to-primate transplantation is to be successful. The presence of preformed antibodies in humans, apes and Old World monkeys directed against galactose epitopes on pig vascular endothelium provides the major barrier, as binding of antibody to antigen leads to graft destruction by complement activation and other mechanisms. Hyperacute rejection can result from the action of complement. If this is prevented, delayed antibody-mediated rejection develops, which can be associated with a state of consumptive coagulopathy (disseminated intravascular coagulation, DIC). Efforts being made to overcome antibody-mediated rejection include depletion of antibody by extracorporeal immunoadsorption, prevention of an induced antibody response by co-stimulatory blockade, B-cell and/or plasma cell depletion, depletion or inhibition of complement, or the use of organs from pigs transgenic for a human complement regulatory protein, such as hDAF. The ultimate solution would be the induction of both B- and T-cell tolerance to the transplanted pig organ, which is being explored by attempting to induce haematopoietic cell chimerism. One complication of this is a thrombotic microangiopathy, similar to thrombotic thrombocytopenic purpura. The many and diverse roles in which pharmacotherapy is involved in attempts to overcome the barriers of xenotransplantation are reviewed and current progress, particularly in our own laboratory, is discussed.
 ...
PMID:Pharmacotherapeutic agents in xenotransplantation. 1124 14

The application of phenol to the femoral veins of anesthetized dogs resulted in an occluding thrombus in 24 of 25 veins at 1 week. Serial venography and eventual histology showed that these veins remained occluded over a 5-week observation period, the thrombi undergoing organization. Therapeutic defibrination was achieved with administration of an enzyme from venom of the pit viper (Arvin). Arvin, administered for 1 week immediately following phenol application and before thrombus formation had occurred, prevented thrombosis in all 10 such veins, and serial venography for a further 4 weeks showed that the veins remained patent. Administration of Arvin was begun 24 hours postoperatively, when venography had demonstrated an occluding thrombus and failed to clear any of 11 veins after 3 weeks of treatment. Intravenous administration of heparin, 10,000 units, at 6, 6, and 12-hour intervals in a 24-hour period, was begun immediately after phenol application and continued for 1 week; 10 of 12 veins were blocked at 1 week. Following the same dose of heparin every 6 hours four of eight veins were blocked at 1 week. The results indicate that when the vascular endothelium is damaged, therapeutic defibrination is more effective than heparin therapy in preventing venous thrombosis. Arvin therapy has no significant thrombolytic effect even if the thrombus is less than 24 hours old.
 ...
PMID:Therapeutic defibrination and heparin therapy in the prevention and resolution of experimental venous thrombosis. 1199 12


<< Previous 1 2 3 4 Next >>