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

---

Query: EC:3.4.21.6 (thromboplastin)
13,278 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

(2R, 4R)4-methyl-1-[N alpha-(3-methyl-1,2,3,4-tetrahydro-8-quinoline- sulfonyl)-L-arginyl]-2-piperidine carboxylic acid monohydrate (MCI-9038) was found to be a potent synthetic inhibitor of thrombin. In concentrations as low as 1 microM, the thrombin time, prothrombin time, and partial thromboplastin time were more than doubled. The venom (Bothrops atrox) time was similarly prolonged. The drug also inhibited the thrombin-induced activation of factors VIII and XIII. While MCI-9038 in concentrations of 10(-4) M had no effect on platelet aggregation induced by collagen, ADP, epinephrine, and arachidonate, nanomolar concentrations inhibited thrombin-induced platelet aggregation and the release of platelet ADP. The drug also significantly inhibited the adhesion of thrombin-treated platelets to cultured bovine aortic endothelial cells. We conclude that MCI-9038 is an extremely potent inhibitor of the effects of thrombin on platelets and clotting factors.
...
PMID:In vitro studies of a new synthetic thrombin inhibitor. 398 96

This study explores the effects on some hematological parameters of a low-dose aspirin regimen (50 mg/day) versus a conventional aspirin treatment with reported antithrombotic efficacy (324 mg/day), in patients with acute myocardial infarction. Fifteen patients were randomized into 3 equal groups receiving 50 mg or 324 mg aspirin or placebo, daily for 21 days. Compared with placebo, bleeding time was significantly and similarly prolonged with both aspirin doses (+ 71 +/- 22% and + 69 +/- 20%, mean +/- S.D.). Aspirin 50 mg/day suppressed arachidonate-induced platelet aggregation and secondary phase aggregation after ADP and adrenaline. Collagen aggregation was inhibited by 44 +/- 15%. In no case were differences in the antiplatelet effects of the two doses observed. The effects of 50 mg/day persisted without attenuation during the observation period. Platelet thromboxane B2 generation during arachidonate-induced aggregation was inhibited by 95 +/- 2 and 99 +/- 1% compared to placebo group after 50 and 324 mg/day, respectively (P between doses less than 0.05). No change was observed with any treatment in coagulation time, prothrombin time or plasma thromboplastin time. Thus, in patients with acute myocardial infarction, the antiplatelet effects of aspirin 50 mg/day are stable over time and superimposable on those of 324 mg/day. The antithrombotic efficacy of aspirin 50 mg/day remains to be tested clinically.
...
PMID:Equal antiplatelet effects of aspirin 50 or 324 mg/day in patients after acute myocardial infarction. 408 90

The effects of 9 beta-methyl carbacyclin, a chemically stable analogue of epoprostenol (prostacyclin, PGI2) were studied, in comparison with epoprostenol, both in vitro and in vivo in man. In vitro 9 beta-methyl carbacyclin and epoprostenol inhibited platelet aggregation induced by ADP, collagen, the endoperoxide analogue U46619 and arachidonic acid. The potency of 9 beta-methyl carbacyclin relative to epoprostenol was comparable in ADP and collagen-aggregated platelet rich plasma (PRP), 9 beta-methyl carbacyclin being 0.01 times as active as epoprostenol. The anti-aggregatory potencies of the two compounds were comparable in PRP and whole blood. The phosphodiesterase inhibitor isobutyl methyl xanthine enhanced the anti-aggregatory activity of both compounds in vitro. 9 beta-methyl carbacyclin and epoprostenol elevated platelet cyclic AMP, 9 beta-methyl carbacyclin being 0.04 times as active as epoprostenol. In a placebo controlled trial both drugs produces significant headache and facial flushing when compared with placebo. Nasal stuffiness, abdominal discomfort and nausea were reported on all three treatments. Both drugs caused significant and comparable increase in heart rate and decrease in pre-ejection (PEP) and PEP/left ventricular ejection time (LVET) ratio compared with placebo. Systolic and diastolic blood pressure, LVET and QS2 index were unchanged. Platelet aggregation responses to ADP were significantly inhibited by all three doses of both drugs compared with placebo. Bleeding time was significantly longer during epoprostenol infusion than either placebo or 9 beta-methyl carbacyclin infusion. Neither drug had significant effect, compared with placebo, on kaolin activated clotting time in PPP, PRP or in PRP in the presence of heparin, prothrombin time, partial thromboplastin time, thrombin clotting time, fibrinogen, fibrinogen degradation products or euglobulin clot lysis time. The pharmacodynamic effects and duration of action of 9 beta-methyl carbacyclin and of epoprostenol are similar; 9 beta-methyl carbacyclin is approximately 100 times less potent than epoprostenol in man.
...
PMID:A chemically stable analogue, 9 beta-methyl carbacyclin, with similar effects to epoprostenol (prostacyclin, PGI2) in man. 608 4

A double blind study was performed on 20 atherosclerotic patients. A placebo was administered to one group of 10 patients (group A) and ticlopidine (500 mg/day) was administered to another group of 10 patients (group B) for one month. ADP and collagen-induced platelet aggregation (PA), platelet malondialdehyde (MDA) produced by thrombin stimulation and plasma beta-thromboglobulin (beta TG) levels, prothrombin time, activated partial thromboplastin time (APTT) fibrinogen, antithrombin (AT) III fibrin(ogen) degradation products, alpha 2-antiplasmin and plasminogen were evaluated in both groups before and after treatment. No changes in PA, MDA and beta TG were seen in group A. Group B showed a significant decrease of PA, beta TG and a significant increase of MDA. No changes on blood coagulation data were seen in either group. This study suggests that ticlopidine is able to inhibit platelet function in vivo.
...
PMID:Effects of ticlopidine on platelet function and blood coagulation. 621 77

Porcine mucosal heparin was chemically depolymerized. The depolymerization was stopped at different steps to obtain two low molecular weight (LMW) heparins with a molecular weight of 10 000 and 6000, respectively. The LMW heparins were tested in vitro for anti-clotting activities and for platelet serotonin release in different systems in comparison with normal heparins, dermatan and heparan sulphate. After addition of various amounts of heparin preparations to washed platelets, no significant release was observed for all tested heparins. On the contrary, different heparins showed an inhibition of serotonin-release induced by collagen in platelet rich plasma, whereas the ADP-induced release was increased. The effect on the platelet release appears related to the molecular weight. In fact, it is significant only for normal heparins whereas it is not for LMW heparins. A good relation was observed, also, between anti-activated factor X activity/antiglobal clotting activity (Xa/APTT) ratio of different heparins and the effect on platelet release.
...
PMID:Normal and low molecular weight heparins: interaction with human platelets. 622 24

Normal plasma exposed to an insolubilized omega-NH2-hexyl-agarose derivative of PGE1 inhibits ADP-induced platelet aggregation. To define the plasma macromolecule responsible, we tested plasma congenitally deficient in coagulation factors for this property. Only plasma deficient in factor X failed to inhibit platelet aggregation under these conditions. The inhibition could be restored by reconstituting the defective plasma with bovine or human factor X. Purified factor X or Xa exposed to insolubilized PGE1 also inhibited ADP-induced platelet aggregation. Factor Xa could reverse suggesting that factor Xa was the responsible component. This conclusion was further supported by the ability of heparin to reverse the inhibitory effect of altered factor Xa when the anticoagulant was added simultaneously to platelets. The results were not due to the release of PGE1 from the insoluble derivative. Factor Xa may have a heretofore unrecognized effect on modulating platelet functions.
...
PMID:Cyclic AMP independent inhibition of platelet aggregation by prostaglandin E1 is mediated through factor Xa. 631 Aug 17

With current technological advances, it is now possible to measure in less than 50 microL of plasma picomolar amounts of circulating products of platelet activation, products of protease activation related to coagulation and fibrinolytic pathways, and prostaglandin metabolites formed during a physiologic or pathologic process. Most of these markers, which circulate in blood in nanogram or picogram amounts per milliliter during or after pathologic activation, provide pertinent information on the status of a patient in terms of specificity and early detection, and will be of crucial value in the diagnosis of hemostatic defects and the management of newer antithrombotic drugs that cannot be monitored by currently available assays. Currently, 125I- and 3H-based simple radioimmunoassays are available for platelet factor 4, beta-thromboglobulin, fibrinopeptide A, B beta 15-42 related peptides, thromboxane B2, and the prostaglandins 6-keto-PGF1 alpha and PGE2. Nonisotopic methods such as enzyme-linked immunosorbent assays and fluoroimmunoassays are being developed. Serotonin and ADP, products of platelet activation, are measurable by liquid-chromatographic, immunoenzymatic, and spectrophotofluorometric methods. Analytical methods for fibrin split products (fragments D and E) and serine protease inhibitor complexes such as thrombin-antithrombin-III, factor Xa-antithrombin-III, and kallikrein-C1-esterase are also being developed. We have evaluated all of these methods and found them to be very sensitive to those components of endogenous activation of the hemostatic system listed above.
...
PMID:Molecular markers of hemostatic disorders: implications in the diagnosis and therapeutic management of thrombotic and bleeding disorders. 634 55

Two family members (daughter and mother) with a bleeding disorder showed prolonged bleeding time and activated partial thromboplastin time associated with decreased plasma levels of factor VIII procoagulant activity, factor VIII-related antigen, and factor VIII-ristocetin cofactor activity. The ristocetin-induced platelet agglutination (RIPA) was enhanced, ADP-, collagen- and Ca ionophore-induced platelet aggregation were also increased at low concentrations of these compounds. In the mother, spontaneous platelet aggregation (SPA) was also observed. Contrary to type II B von Willebrand's disease (vWd), pseudo-vWd and platelet-type vWd, the patients did not show any increased binding of factor VIII/vWf to platelets in the presence of ristocetin. The RIPA in normal controls were inhibited by addition of antifactor VIII antiserum to the platelet-rich plasma, but not in cases 1 and 2. In this atypical vWd, therefore, the hyperreactivity of platelet aggregation may be due to an intrinsic abnormality of the platelets, but not to any enhanced interaction between plasma factor VIII and the platelets.
...
PMID:An atypical von Willebrand's disease with hyperreactivity of platelet aggregation. 642 80

The effects of treadmill exercise (up to 85% of the predicted maximum heart rate) on platelet functions and coagulating activities were studied in 26 normal men. Blood sampling for the measurements were performed from the antecubital vein at rest, at 3, 6, 9, and 12 min during exercise, immediately postexercise, and at 6 and 30 min after exercise. Measurements for blood analysis included the following: platelet sensitivity and percent aggregation to ADP, platelet counts, plasma thromboxane B2 and 6-keto-prostaglandin F1 alpha levels, plasma epinephrine and norepinephrine levels, plasma fibrinogen level, activity of plasma antithrombin III, and of plasma factors VIII, IX, XI, and XII. No significant changes were induced by dynamic leg exercise in platelet sensitivities and the maximum and 3-min percent aggregation. The platelet counts increased during exercise in platelet-rich plasma without a significant change in that in whole blood. During exercise, plasma thromboxane B2 levels showed a tendency to increase, while plasma 6-keto-prostaglandin F1 alpha levels to decrease. Plasma epinephrine levels showed a tendency to increase and norepinephrine levels increased during exercise. Among coagulating factors, factor VIII activities and fibrinogen levels increased without altering activities of factors IX, XI, and XII. Antithrombin III activities also increased during exercise. In spite of significant changes in several coagulating factors, prothrombin time and partial thromboplastin time were not influenced by exercise. In conclusion, dynamic leg exercise of a moderate to high intensity produced a significantly elevated plasma level of factor VIII, fibrinogen, antithrombin III, and catecholamines without affecting the hemostatic balance in normal subjects.
...
PMID:Effects of treadmill exercise on platelet functions and blood coagulating activities in healthy men. 643 Nov 40

The relationship between platelet release and fibrinopeptide A cleavage from fibrinogen to form fibrin I in vitro was examined in blood allowed to clot undisturbed or with gentle agitation. In undisturbed or agitated blood platelet release and fibrin I formation occurred simultaneously. When hirudin was added to undisturbed blood it prevented platelet release as well as fibrin I formation. In contrast, hirudin added to agitated blood had little effect on platelet release despite complete inhibition of fibrin I formation. Collagen added to either undisturbed or agitated blood increased platelet release and then fibrin I formation, and ADP added to undisturbed blood caused an initial burst of platelet release followed by slight acceleration of fibrinopeptide A cleavage. Prostaglandin E1 and theophylline prevented platelet release in both undisturbed and agitated blood, but did not affect fibrin I formation. The results with inhibitors in agitated blood suggest that fibrin I formation and platelet release can occur independently in the presence of the increased interactions induced by agitation. Addition of thrombin or tissue thromboplastin to undisturbed blood accelerated fibrin I formation with little effect on platelet release. Finally, initial thrombin formation in undisturbed blood appeared to be associated with the platelet surface. These relationships suggest that thrombin formation via the intrinsic system leads to thrombin generation on the platelet surface and simultaneous platelet release and fibrin I formation, while thrombin generated via tissue thromboplastin leads to thrombin formation in the plasma and fibrin I formation preceding platelet release. Activation by interaction of blood with collagen causes initial acceleration of platelet release and later acceleration of fibrin I formation.
...
PMID:Fibrinopeptide A cleavage and platelet release in whole blood in vitro. Effects of stimuli, inhibitors, and agitation. 645 36


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---