Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.6 (thromboplastin)
 13,278 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Platelets provide a procoagulant activity for the conversion of prothrombin to thrombin during normal hemostatis. This activity designated as platelet prothrombin-converting activity (PPCA) was monitored as rate of thrombin production in a two-stage assay using gel-filtered bovine platelets, factor Xa, and prothrombin. Expression of PPCA was not associated with ADP-induced release or platelet shape change but was associated with aggregation. Release of the contents of dense bodies, measured by release of 14C-5-hydroxytryptamine, was not required for expression of PPCA during platelet aggregation. During the PPCA assay, 5-hydroxytrypamine was released, but only after onset of thrombin production. Furthermore, the release of 5-hydroxytryptamine was retarded during the assay by the addition of 2 mM theophylline and 100 nM prostaglandin E1 without a comparable reduction in PPCA. In addition, 125I-factor-Xa was bound in greater amounts to platelets (aspirin-treated) after ADP-induced aggregation (without detectable release) than to unactivated control platelets. Finally, the PPCA of the ADP-activated platelets was saturated with respect to factors Xa and Va at less than 1 nM concentrations, indicating that the aggregation induced by ADP leads to the exposure of specific procoagulant sites by some process other than dense body secretion.
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PMID:The effect of aggregation and release on platelet prothrombin-converting activity. 46 34

1. The antithrombotic effect of a new specific thrombin inhibitor, CX-397, was examined in a photochemically-induced arterial thrombosis model in the rat femoral artery and compared with that of heparin. 2. Pretreatment with CX-397 (10, 20 and 40 micrograms kg-1 min-1, i.v.) from 15 min before the experiment prolonged the time required for thrombotic occlusion of the artery in a dose-dependent manner. The antithrombotic efficacy of CX-397 was associated with modest increases in activated partial thromboplastin time (APTT) and template bleeding time. 3. On the other hand, heparin at a dose of 450 micrograms kg-1 markedly prolonged APTT and the bleeding time, but did not inhibit thrombo-occlusion. 4. CX-397 selectively inhibited platelet aggregation and concurrent secretion of 5-hydroxytryptamine (5-HT) and thromboxane A2 (TXA2) production from platelets in response to thrombin, but not to collagen and ADP, in a dose-dependent manner (5-100 ng ml-1). 5. CX-397 at 10 micrograms kg-1 combined with vapiprost, a TXA2 receptor antagonist, at 0.1 mg kg-1 significantly prevented occlusion, whereas, at these doses, neither drug alone had much effect. 6. These results demonstrate that CX-397 may prove to be more efficient for preventing platelet-rich thrombosis than heparin. Thrombin may play an important role in the rat thrombosis model. 7. The additive antithrombotic effect of the combination of thrombin inhibitor and TXA2 receptor antagonist at low doses suggests that thrombin and TXA2 may work in concert to produce thrombosis.
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PMID:Antithrombotic effect of a novel recombinant hirudin analogue, CX-397, in a rat arterial thrombosis model. 868 Jul 43

The aim of the study was to evaluate in a double-blind manner the effect of the long-acting 5-hydroxytryptamine 2 (5-HT2)-receptor blocker Ritanserin on clinical symptoms in patients with fibromyalgia syndrome (FM) and on production of antibodies to serotonin, gangliosides and phospholipids, recently shown to have a high incidence in this disease. Fifty-one female patients with typical FM were included in the 16-week study: 24 received Ritanserin and 27 received a placebo. Antibodies to 5-HT, gangliosides (Gm1) and phospholipids (thromboplastin) were determined by enzyme-linked immunosorbent assay at day 0 and at the end of week 16. The psychological and physical status, including tender points, of the patients was evaluated at day 0 and at the end of weeks 4 and 16. At the end of the study, there was an improvement (p < 0.05) in feeling refreshed in the morning in the Ritanserin-treated group and headache was also significantly improved compared with the placebo group. There was no difference in pain, fatigue, sleep, morning stiffness, anxiety and tender point counts in the Ritanserin and placebo groups. Fifty-one per cent of the 51 patients had at least one of the three antibodies to 5-HT, Gm1 and phospholipids. The incidence and activity of these antibodies were not influenced by Ritanserin or placebo. The observation that Ritanserin has only a small effect on clinical symptoms indicates that disturbances in serotonin metabolism or uptake may be only one factor in the pathogenesis of the disease. The high incidence of a defined autoantibody pattern in FM could again be confirmed in this study. However, it remains speculative whether immunological reactions are, indeed, involved.
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PMID:A randomised double-blind 16-week study of ritanserin in fibromyalgia syndrome: clinical outcome and analysis of autoantibodies to serotonin, gangliosides and phospholipids. 964 2