Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The relative contribution of platelets to plasminogen activator inhibitor (PA-inhibitor) activity in blood was investigated. From the difference in PA-inhibitor levels in platelet-poor plasmas of 12 donors (3 +/- 1 U/ml, mean +/- 95% confidence limits) and in the corresponding platelet-rich plasmas after induction of platelet aggregation by collagen, ADP or epinephrine (7 +/- 1 U/ml), it may be concluded that a greater amount of PA-inhibitor in blood is associated with platelets than with plasma. In collagen-stimulated platelets maximal release of PA-inhibitor and of beta-thromboglobulin (beta-TG) was attained within fifteen seconds, whereas in ADP-stimulated platelets the release of both factors was slower. In platelet-poor plasma no correlation was found between the level of PA-inhibitor and that of beta-TG. Thus, the PA-inhibitor found in plasma is not derived from platelets that had been stimulated after blood collection. The rate of complex formation and the Mr of the principal complexes of radioiodinated tissue-type plasminogen activator (t-PA) or urokinase (UK), in platelet-poor plasma, in platelet-rich plasma after platelet aggregation or in an extract of washed platelets was the same. Moreover, complexes of UK or t-PA with plasmatic PA-inhibitor or with the PA-inhibitor(s) from platelets bound to immobilized antibodies against bovine endothelial cell-derived PA-inhibitor. These results show that the PA-inhibitors in plasma and in platelets are very similar or identical.
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PMID:Studies on the release of a plasminogen activator inhibitor by human platelets. 294 Jul 23

The ex vivo aggregability of rabbit platelets was assessed after rabbits were treated in vivo with thrombolytic doses of tissue plasminogen activator (t-PA) or streptokinase (SK). t-PA was evaluated at 2 doses; an effective thrombolytic dose of 10 micrograms/kg/min, i.v. and a higher dose of 30 micrograms/kg/min, i.v.. At both concentrations, ex vivo platelet hyperaggregability was observed when collagen, arachidonic acid or ADP were employed as the aggregating agonists. Significant falls in circulating platelet counts were observed after t-PA infusion. Infusion of SK also resulted in ex vivo platelet hyperaggregation. These data reveal that thrombolytic therapy may result in hyperaggregable platelets which may play a role in reocclusion of successfully recanalized blood vessels.
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PMID:Tissue-type plasminogen activator and streptokinase induce platelet hyperaggregability in the rabbit. 311 93

Haemostatic variables were assessed in 43 patients, 28 insulin-dependent and 15 non insulin-dependent. Maximum aggregation by low concentrations of adenosine diphosphate (ADP) or arachidonic acid and elevated plasma concentrations of TxB2, Factor VIII, vWF:Ag, RCoF and fibronectin (Fnct) indicated a hypercoagulable state. The manifestation of vasculopathy was associated with elevated concentrations of RCoF, Fnct, Hbalc, cholesterol and triglycerides, while impaired fibrinolysis was demonstrated by decreased t-PA levels and the absence of crosslinked fibrin degradation products (XL-FDP).
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PMID:Diabetes mellitus as a hypercoagulable state: its relationship with fibrin fragments and vascular damage. 311 98

The effect of Norplant subdermal implants on 22 different hemostatic variables was determined in 100 women attending the Fertility Control Clinic of the Singapore National University Hospital before and after 6 and 12 months of use. The factors analyzed were: hematocrit, hemoglobin (Hb), prothrombin time (PT), activated partial thromboplastin time (APTT), platelet count, fibrinogen, coagulation factor II, Factor V,Factor VII, Factor VIII, Factor VIIIR:Ag, Factor X, plasminogen activator, FDP, plasminogen (imm), antithrombin III (functional), antithrombin (antigen), protein C, alpha2-antiplasmin, alpha2-macroglobulin, alpha2-antitrypsin, platelet count, platelet aggregation (ADP), and platelet aggregation (collagen). The factors that differed significantly after 12 months were: Hb,PT,APTT, Factors II,V,VII, and VIIIR:Ag, Plasminogen (imm), antithrombin III(antigen), alpha2-antiplasmin, platelet count, and platelet aggregation. Most of these differences, while significant, were still within the normal range, except for PT,APTT, and platelet count. The subjects were considered to be in an enhanced risk for hypercoagulation and thrombosis.
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PMID:The effects of Norplant-2 rods on clinical chemistry in Singaporean acceptors after 1 year of use: haemostatic changes. 314 69

The long-acting antianginal drug molsidomine has been shown experimentally to reduce myocardial infarct size when administered prior to or after cardiac insult. This is due to several drug actions. Dilation of postcapillary capacitance vessels diminishes venous return, preload, heart dimensions, and myocardial oxygen consumption. Relaxation of stenosed conductive coronary arteries increases the perfusion of myocardial areas at risk of infarction due to enhanced collateral circulation. Increased regional blood supply nourishes predominantly subendocardial cardiac muscles as a result of reduction of extravascular coronary pressure, and resistance. The stable heart rate and cardiac contractility favor improved heart performance. The inhibition of platelet aggregation in vivo by molsidomine or its active metabolites, SIN-1 and SIN-1A, is linked to the stimulation of prostacyclin synthesis, inhibition of thromboxane release with induction of thrombosis and vasoconstriction, and enhanced concentrations of cyclic guanosine monophosphate. Dilation of coronary arteries after intracoronary administration of SIN-1, with inhibition of platelet aggregation by restrained release of adenosine diphosphate and stabilization of platelet membranes, facilitates the recanalization of stenosed arteries and reduces coronary muscle tone at the site of thrombosis. Activation of the human fibrinolytic system and drug-induced release of a plasminogen activator favor dysaggregatory effects. The drug's inhibiting actions on lipoxygenase products of arachidonate (e.g., 12-hydroperoxy-eicosatetraenoic acid and leukotrienes) may shift prostaglandin catabolism to cyclooxygenase products (e.g., prostacyclin) that protect against the expansion of ischemia and the induction of coronary spasm. Experimentally, the hemodynamic effectiveness of molsidomine can be antagonized by catecholamines (afterload effects) and dihydroergotamine (preload and afterload effects) respectively. Further clinical investigations will clarify the application of these mechanisms for the therapeutic success of the drug in human myocardial infarction.
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PMID:Molsidomine: alternative approaches to treat myocardial ischemia. 355 58

DNA repair is an important mechanism of chemotherapy resistance in common human tumours. The normal tissues tolerate the drugs also, hence elucidation of normal pathways, rather than markedly resistant mutants, is more likely to be relevant. Specific repair mechanisms may deal with certain lesions (eg O6-methylguanine) but other more general mechanisms (excision repair, poly ADP ribose) can handle a wide range of lesions. The response of human cells to DNA damage is more complex than simply removing lesions. Interactions with growth factors, induction of receptors for growth factors, production of soluble mediators and secretion of plasminogen activator are parts of a cellular and tissue response. These processes may be more active in earlier, less differentiated cells which are more resistant to radiotherapy and chemotherapy. The genetic instability of cancer cells may be related to inappropriately activated DNA repair pathways.
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PMID:DNA repair and resistance to chemotherapy. 391 57

The release and the local activity of plasminogen activator (PA) were studied in isolated perfused dog hearts, without or with intimal injury induced by means of a balloon catheter inserted into the left anterior descending coronary artery (LAD). Thrombin but not DFP-thrombin induced a dose-dependent PA release in doses of 8 to 32 units. ADP 20 or 200 mumol but not ergonovine 20 or 200 micrograms induced a weak PA release. The local PA activity was much lower in the LAD at 1 or 4 weeks after this injury than in the intact LAD. However, the release of PA from the hearts after intimal injury was similar to findings in the intact hearts. We conclude from this study that thrombin plays an important role in regulating the coagulation-fibrinolysis system in endothelial cells and that changes in the properties of the endothelial cells may lead to initiation and enhancement of atherosclerosis.
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PMID:Release of plasminogen activator from isolated perfused dog heart. 403 71

There is an increased frequency of arterial thrombosis in cigarette smokers. The changes in blood coagulation seen in these subjects have been studied by many workers but results have not always been in agreement. We wished to study the effects of acute smoking on platelet behaviour, fibrinolysis and haemorheology in ten habitual smokers, and to compare these results with non-smoking controls. Results show that the smoking group had higher plasma fibrinogen (p less than 0.04), lower plasminogen (p less than 0.02) and plasminogen activator (p less than 0.05), and higher plasma viscosity (p less than 0.003). The changes seen in cigarette smokers after smoking three cigarettes were an increase in the rate of platelet aggregation to ADP (p less than 0.02), an increase in alpha 2M, (p less than 0.02), and factor VIII RAG (p less than 0.05). Plasma viscosity was decreased (p less than 0.02) as was red cell deformability (p less than 0.02). We confirm an increased tendency to hypercoagulability in smokers compared to controls which becomes more pronounced immediately after smoking three cigarettes.
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PMID:The effects of acute smoking on platelet behaviour, fibrinolysis and haemorheology in habitual smokers. 623 29

In order to compare the metabolic and hemobiological properties of two sulfonylureas, thirty-five non-insulin-dependent diabetics were randomly assigned to two groups. Each group was given either gliclazide (n = 20) or glibenclamide (n = 15) for six months. Metabolic control was improved in both groups, as evidenced by the decrease in HbA1 concentrations. A significant fall in ADP (1 and 4 microM)--induced platelet aggregation was recorded in the gliclazide group, while antithrombin III levels remained normal throughout the trial and plasminogen activator levels increased. These hemobiologic changes may be effective in preventing the vascular complications of diabetes. In contrast, glibenclamide did not alter platelet aggregation. Furthermore, a significant decrease in both antithrombin III levels and basal and venostasis-stimulated plasminogen activator levels were seen in glibenclamide patients. The beneficial changes in hemostasis seen in gliclazide patients probably result from a direct effect of the drug since hemobiological parameters and metabolic control parameters were not correlated.
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PMID:[Effects of gliclazide and glibenclamide on platelet function, fibrinolysis and metabolic control in diabetic patients with retinopathy (author's transl)]. 628 3

The absence of fibrinogen and the presence of plasmic fragments X, Y, D, and E were demonstrated in a patient bitten by a western diamondback rattlesnake, Crotalus atrox. The factor VIII level and the platelet count were within normal limits. There were distinct changes of protease inhibitors in the patient's plasma. Alpha-1-protease inhibitor was elevated. Antithrombin-III was only slightly decreased after the envenomation, but alpha 2-antiplasmin and alpha 2-macroglobulin were initially significantly lowered, returning to normal values in 38 and 3 days, respectively. Plasmin-alpha 2-antiplasmin complex was present until day 10 after the envenomation. However, purified plasminogen was not activated in vitro by the venom. Cultured endothelial and smooth muscle cells from human blood vessels released an increased amount of plasminogen activator upon incubation with the venom. The release did not result from cell lysis. Platelets in normal human platelet-rich plasma were aggregated by 10 micrograms/ml of the venom, without serotonin secretion. The aggregation kinetics and serotonin secretion induced by adenosine diphosphate (ADP) or arachidonate were not significantly affected by the venom at 1-10 micrograms/ml. It is concluded that the predominant mechanism of afibrinogenemia in the patient after Crotalus atrox bite resulted from primary fibrinogenolysis and not from a consumptive coagulopathy. The lytic state seemed to be induced through an indirect activation of plasminogen by vascular plasminogen activator, which was probably released from endothelial cells and smooth muscle cells by the snake venom.
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PMID:Fibrinogenolytic afibrinogenemia after envenomation by western diamondback rattlesnake (Crotalus atrox). 653 96


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