Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.68 (tissue plasminogen activator)
 11,311 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A newly developed low molecular weight heparin (LU 47311) was given to 6 healthy volunteers (males, mean age: 30.5 years, range: 20-39 years). They obtained a single dose of 40 and 60 anti FXaU per kg body weight, respectively, by subcutaneous administration. The anti FXa elimination half-life was close to 3 hours. The APTT showed slight response following high dose. No significant influence on fibrinolysis as measured by t-PA and PAI assays was noticed. There was no clear evidence of enhancement of platelet function when detected by Born's method and platelet factor 4 and beta-thromboglobulin assays. However, a moderate but significant increase of thromboxane B2 was noticed in the group obtaining an elevated dose of LMW heparin. Serum levels of triglycerides and cholesterol remained unaltered. The aminotransferases, electrolytes, renal function parameters and cell counts of the peripheral blood were not influenced by LMW heparin.
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PMID:Study of a new low molecular weight heparin (LU 47311) administered to healthy volunteers. 248 3

Heparin and a low molecular heparin fragment, injected intravenously in volunteers, increased the plasma concentrations of platelet factor 4, but did not induce platelet activation as judged from excretion of 2,3-dinor-TxB2 (a major thromboxane A2 metabolite) and beta-thromboglobulin (btg) in urine and from btg levels in plasma. Heparin prolonged, within the normal range, the bleeding time in all six subjects. Platelet aggregation in platelet rich plasma was potentiated by both heparins, but platelet number, mean platelet volume and platelet distribution width were not affected. No evidence for endothelial release of prostacyclin was obtained as judged from urinary excretion of 2,3-dinor-6-keto-PGF1 alpha (a major prostacyclin metabolite), and plasma concentrations of tissue plasminogen activator, its inhibitor (PAI-1) and the von Willebrand-factor were unchanged.
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PMID:Immediate effects of heparin and LMW heparin on some platelet and endothelial derived factors. 284 53

We prospectively examined early changes in platelets and plasma proteolytic systems in 12 vaccinated and 6 unvaccinated volunteers in whom Rocky Mountain spotted fever developed after challenge with Rickettsia rickettsii. The platelet counts declined while the plasma concentration of beta-thromboglobulin and the ratio of beta-thromboglobulin to platelet factor 4 increased, indicating in vivo activation of platelets. Plasma levels of antithrombin III decreased and levels of fibrinopeptide A increased, indicating in vivo activation of the coagulation system. Plasma fibrinogen levels peaked at 24 hours and gradually declined; this is consistent with the behavior of fibrinogen as an acute-phase reactant. Prolongation of the prothrombin time and a decrease in plasma levels of factor VII in the absence of evidence of liver injury suggested possible activation of the extrinsic pathway of coagulation. A decline in plasma prekallikrein levels with an increase in plasma C1-inhibitor-kallikrein complexes suggested activation of kallikrein, probably through the intrinsic coagulation system. Elevations in levels of plasma fibrin-degradation products and alpha 2-antiplasmin-plasmin complexes with declines in plasminogen and alpha 2-antiplasmin levels provided evidence of activation of the fibrinolytic system. Elevated plasma levels of tissue plasminogen activator and von Willebrand factor reflected endothelial stimulation. Thus, even early in the course of Rocky Mountain spotted fever that is treated promptly, there is activation of platelets, coagulation pathways, and the fibrinolytic system. These changes may be related to endothelial perturbation, a major pathogenetic mechanism in the disorder.
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PMID:A prospective study of platelets and plasma proteolytic systems during the early stages of Rocky Mountain spotted fever. 296 2

A two stage method for determination of plasminogen activator inhibitor (PAI) activity in blood plasma is described. In the first stage, an excess of single-chain tissue plasminogen activator (t-PA) is added to plasma. In the second stage, the residual t-PA activity is determined with a plasminogen/chromogenic plasmin substrate assay utilizing poly-D-lysine as a t-PA stimulator. The method proved accurate since it correctly determined the PAI activity (range 0 to 110U/mL) in citrated plasma samples with levels established by time course analysis of t-PA inhibition and by titration with t-PA. Furthermore, correlation was excellent (r = 0.97) with the method of Chmielewska et al Thromb. Res. 31, 427-436, 1983. Plasma samples with increased platelet factor 4, indicative of platelet release, did not show increased levels of PAI activity.
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PMID:Determination of plasminogen activator inhibitor in plasma using t-PA and a chromogenic single-point poly-D-lysine stimulated assay. 313 38

In this study, we demonstrate the presence of a previously undescribed fibrinolytic inhibitor in human serum. It has an apparent molecular weight of 50,000 and is not detected in serum derived from platelet-poor plasma, suggesting that it originates from platelets. This conclusion is supported by a number of observations. For example, extracts of washed, gel-filtered human platelets contain an inhibitor of similar activity and size, and physiological concentrations of thrombin induce its release from the platelets. Moreover, the kinetics and dose dependency of this release are similar to those observed for the release of platelet factor 4, and the release of both molecules is blocked by pretreating the platelets with prostaglandin E1 and theophylline. Mixing experiments, which were devised to investigate the specificity of the inhibitor, showed that the fibrinolytic activity initiated by both urokinase and tissue-type plasminogen activator was blocked by platelet releasate in a dose-dependent manner. In both cases, the amount of inhibition increased when the releasates were preincubated with the purified activators, indicating a direct interaction between the activators and an inhibitor(s). The inhibitory activity was removed by preincubating the releasates with antiserum prepared against an antiactivator purified from cultured bovine aortic endothelial cells. These results indicate that platelets contain an inhibitor which is released by thrombin, inhibits both urokinase and tissue-type plasminogen activator, and is immunologically similar to an inhibitor produced by endothelial cells. This molecule may represent a new class of inhibitors, the antiactivators, which function together with alpha 2-antiplasmin to regulate the fibrinolytic system of the blood. Its release from platelets by thrombin may protect the growing thrombus against premature dissolution initiated by plasminogen activators released by the endothelium.
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PMID:Detection and partial characterization of an inhibitor of plasminogen activator in human platelets. 643 94

The effects of acute smoking on hemostatic functions were investigated in healthy young volunteers. Immediately after the volunteers smoked, a significant increase in blood pressure and heart rate was accompanied by a rise in plasma epinephrine. Fibrinopeptide A and thrombin-antithrombin III complex as markers of thrombin generation in vivo were significantly increased after smoking. The increase in thrombin-antithrombin III complex was significantly correlated with that of plasma epinephrine. Both antigen and activity of tissue plasminogen activator and plasmin-inhibitor complex as markers of fibrinolytic activity in vivo were markedly increased after smoking, whereas D-dimer, plasminogen activator inhibitor antigen, fibrinogen, and both beta-thromboglobulin and platelet factor 4 as markers of platelet activation in vivo were not changed. No effects were observed after sham smoking under exactly identical conditions in the same subjects. Thus thrombin generation was observed as acute hemostatic effects of smoking. Enhanced fibrinolytic response may counteract an increased procoagulant activity. Patients with vascular disease might be more susceptible to a state of disequilibrium in favor of coagulation, which may partly explain a mechanism by which cigarette smoking leads to cardiovascular morbidity and mortality.
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PMID:Thrombin generation as an acute effect of cigarette smoking. 801 87

The influence of erythropoietin therapy on platelet function and fibrinolysis was evaluated in 12 anemic hemodialysis patients. Six months of therapy with human erythropoietin (50 to 80 IU/kg initially) raised the hemoglobin level to 10.8 g/dl but did not increase platelet activity in vivo as measured by beta-thromboglobulin or platelet factor 4. There was no change in the platelet aggregation thresholds in vitro for ADP, adrenaline, thrombin or collagen during treatment. Platelet number and volume were also unaffected. Fibrinolytic activity intensified as erythropoietin treatment proceeded, with a fall of euglobulin clot lysis time and rise in the activity of t-PA. PAI-1 levels also showed a downward trend, without reaching significance. Thus erythropoietin treatment in modest doses does not seem to adversely influence the hemostatic system in patients on hemodialysis.
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PMID:The effect of erythropoietin on platelet function and fibrinolysis in chronic renal failure. 805 Aug 4

The occurrence of thrombotic events remains an important clinical problem in Essential Thrombocythemias (ET). Thus, hemostatic, fibrinolytic and vascular status was investigated in 16 patients (5 males and 11 females) with ET. Among them five presented thromboses in their past history. Platelet hyperactivation, as evidenced by a mean three-fold increase in plasma betathromboglobulin (beta TG), was observed in 13 among 16 patients; surprisingly this activation was present even when the platelet count was normal (in two patients) or subnormal, below 600 x 10(9)/l (in 11 patients). The mean value was 104 +/- 57 IU/ml significantly different from that of normal controls (35 +/- 16.5 IU/ml) (p < 0.001). An artefactual in vitro platelet activation was ruled out by the concomitant measurement of platelet factor 4 (PF4). D-dimers fibrin degradation products (D-Di FDP) were normal in all patients. Vascular endothelial cell function parameters were not markedly modified. The mean value of plasma thrombomodulin (TM) was found slightly but not significantly increased (60.1 +/- 4.9 ng/ml versus 49.1 +/- 10.0 ng/ml in controls). The values of plasma TM correlated neither with that of the platelet count nor with that of plasma beta TG or plasma PF4. The mean values of plasma protein S, von Willebrand factor (vWF), plasminogen activator inhibitor type 1 (PAI-1), tissue plasminogen activator (tPA) were normal and were not correlated neither with that of plasma TM nor with that of plasma beta TG.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Platelet hyperactivation in patients with essential thrombocythemia is not associated with vascular endothelial cell damage as judged by the level of plasma thrombomodulin, protein S, PAI-1, t-PA and vWF. 771 May 37

Thirty healthy young women, non-smokers and of normal weight, used a combined oral contraceptive consisting of 20 micrograms ethinylestradiol and 150 micrograms desogestrel for 9 cycles. Before and during the 3rd, 6th and 9th cycles of contraceptive use, the following parameters were measured: triglycerides, total cholesterol, HDL-cholesterol, apolipoprotein A and B, prothrombin time, partial thromboplastin time, fibrinogen, antithrombin III, protein C, plasminogen, antiplasmin, tissue plasminogen activator, platelet count, platelet aggregation, beta-thromboglobulin and platelet factor 4. The ratios of total cholesterol/HDL-cholesterol and apolipoprotein A/B remained constant or showed only a slight increase. The clotting/fibrinolytic balance showed a similar trend. There was however, an inconstant but significant increase in antithrombin III and protein C. Platelet count and platelet function parameters were unmodified. Hence the contraceptive induced no substantial changes in lipid balance or blood clotting, at least during the study period.
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PMID:Evaluation of risk of thrombosis during use of low-dose ethinylestradiol-desogestrel oral contraceptive. 823 74

In 15 patients with systemic sclerosis (SS) and 8 patients suffering from silicosis and/or silica dust exposure-associated scleroderma (SAS), various parameters of endothelial cell and platelet function and of blood coagulation and fibrinolysis were studied. In 9 of the 23 patients the values for the von Willebrand factor antigen were increased, and the same applied to the endothelin levels in 8 of 23 patients. Protein C, protein S, anti-thrombin III and tissue plasminogen activator (before and after 10 min venous occlusion) were normal. The plasminogen activator inhibitor, however, was increased in 5 patients. Increased levels of platelet factor 4 and of beta-thromboglobulin were found in 20 patients, while the ADP- and epinephrine-induced platelet aggregation was reduced in 5 patients. No individual patient was found to have a general disturbance of all parameters. The deviations in the parameters of endothelial cell and platelet function and of blood coagulation and fibrinolysis proved to be rather inconsistent. This suggests different functional stages in dependence on the various influential factors. There was no close correlation either with the severity of Raynaud's phenomenon or with the type of SS. In addition, there were no basic differences between SS and SAS. The disturbances occurred with similar frequency and in similar proportions in both disease groups.
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PMID:[Vascular function parameters in idiopathic and quartz-induced progressive scleroderma]. 827 90


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