Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.5 (thrombin)
 33,306 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To develop a more potent antithrombin agent with thrombolytic and antiplatelet properties, a new staphylokinase (SAK) variant was constructed. The kringle 2 domain (K2) of tissue type-plasminogen activator (t-PA) containing a fibrin-specific binding site (i), the RGD sequence (Arg-Gly-Asp) for the prevention of platelet aggregation (ii) and the antithrombotic agent - hirulog (iii) was assembled to the C-terminal part of recombinant staphylokinase (r-SAK). cDNA for the hybrid protein SAK-RGD-K2-Hirul was cloned into Pichia pastoris pPIC9K yeast expression vector. The introduction of K2 t-PA, the RGD sequence and hirulog into the C-terminus of r-SAK did not alter the staphylokinase activity. We observed a higher clot lysis potency of SAK-RGD-K2-Hirul as evidenced by a faster and more profound lysis of (125)I-labeled human fibrin clots. The potency of thrombin inhibition by the hirulog C-terminal part of the recombinant fusion protein was almost identical to that of r-Hir alone. These results suggest that the SAK-RGD-K2-Hirul construct can be a more potent and faster-acting thrombolytic agent with better antithrombin and antiplatelet properties compared to r-SAK and SAK-RGD-K2-Hir.
Acta Biochim Pol 2009
PMID:Cloning and expression of a new recombinant thrombolytic and anthithrombotic agent - a staphylokinase variant. 1901 30

The purpose of this study was to determine changes in coagulation profile parameters in cattle with left abomasal displacement (LAD). The study was performed on 20 Holstein-Friesian (H-F) cows divided into two groups: group I--10 cows with diagnosed left abomasal displacement and group II--10 clinically healthy cows. Coagulation tests, including TT (thrombin time), PT (prothrombin time) and APTT (activated partial thromboplastin time), were conducted, and fibrinogen content, D-dimer content, AT III (antithrombin III) activity and platelet (PLT) count were determined in all the animals. Prolonged TT, PT and APTT, a higher fibrinogen and D-dimer content, a drop in AT III activity and thrombocyte count were observed in the cattle with LAD. The above abnormal coagulation profiles were most predominant in three cows which died after surgical repositioning of the abomasum. The results of the study indicate that in cattle with abomasal displacement, the disseminated intravascular coagulation (DIC) syndrome was the most significant risk factor for mortality.
Pol J Vet Sci 2008
PMID:Changes in the coagulation profile of cattle with left abomasal displacement. 1922 27

The results of 3 large randomized trials of activated factor X inhibitors, for the prevention of venous thromboembolism, recently became available. Similar data for orally active thrombin inhibitors is also available from recent trials. In this review, we attempt to provide a balanced perspective on the relative merits and demerits of the new, orally active anticoagulants, and speculate on the future of these agents in clinical practice.
Pol Arch Med Wewn
PMID:New oral anticoagulants: not quite there yet. 1934 Nov 79

The current study systematically evaluates the in vitro effect of eptifibatide, a GPIIb/IIIa blocker, on various responses of porcine platelets evoked by principal physiological stimulators. Eptifibatide at concentrations up to 40 mg/mL did not affect the calcium signal produced by thrombin, partly reduced the procoagulant response evoked by collagen, and strongly inhibited (IC50 approximately 11 mg/mL) adhesion of these cells to fibrinogen coated surfaces. Eptifibatide in a concentration-dependent manner reduced ADP, collagen, and thrombin-induced platelet aggregation (IC50 = 16-27 mg/mL), dense granule secretion (IC50 = 22-31 mg/mL) and lysosome secretion (IC50 = 25-50 mg/mL). Substantial (up to 30-40%) collagen or thrombin-evoked platelet aggregation still occurred at high (52 mg/mL) eptifibatide concentrations. Direct comparison of the susceptibility of platelet aggregation and dense granule secretion to the inhibitory action of eptifibatide indicates that aggregation is appreciably more sensitive than secretion. Eptifibatide (8 mg/mL) added together with a low (70 ng/mL) concentration of bivalirudin (a direct thrombin inhibitor) effectively (approximately 90%) reduced platelet aggregation induced by thrombin (0.2 U/mL). Based on these results, eptifibatide is not expected to reduce efficiently thrombus formation initiated by rapid local production of large amounts of thrombin. One practical consequence of our in vitro studies is the suggestion that the anti-thrombotic efficacy of eptifibatide, especially in preventing acute thrombotic events, may be largely improved by its combination with direct thrombin inhibitors.
Acta Pol Pharm
PMID:The in vitro effect of eptifibatide, a glycoprotein IIb/IIIa antagonist, on various responses of porcine blood platelets. 1964 23

5,10-methylenetetrahydrofolate reductase (MTHFR) is the key enzyme in folate, methionine and homocysteine metabolism. The disturbances in MTHFR activity could be the cause of increased serum level of homocysteine. Hyperhomocysteinemia is a risk factor of changes in coagulation cascade through direct cytotoxic influence on endothelium, atherogenesis, activation of coagulation factor V and VII, increased level of thrombin and platelets aggregation. Genetic disturbances in MTHFR enzyme activity in the presence of polymorphic variants of its gene are responsible for homocysteine augmentation and could be the reason of several gestational complications such as recurrent miscarriages.
Ginekol Pol 2009 Oct
PMID:[Genetic conditioned changes in activity of 5,10-methylenetetrahydrofolate reductase (MTHFR) and recurrent miscarriages]. 1994 41

Platelets (PLT) are the smallest yet highly reactive components of the circulatory system. Microvesicles (platelet-derived microvesicles - PMV), also known as microparticles or microplatelets (platelet-derived microparticles - PMP), are released from platelets upon stimulation by thrombin, collagen or others platelet agonists. Both PLT and PMP play a role in haemostasis and mediate signal transmission between cells, especially cancer cells, thus modulating their functions. Moreover, these two platelet populations participate in transcellular exchange of information, affect immune responses and angiogenesis, which may facilitate tumour growth and development of distant metastases. Their role in tumour progression has been recognized, but the mechanism of their action remains still unclear. Assessment of PMP as a diagnostic and prognostic marker in various disorders is currently a subject of intense investigation.
Pol Merkur Lekarski 2009 Dec
PMID:[A new look at platelets and microparticles, including their role in haemostatic disorders and progression of neoplastic disease]. 2012 Jul 15

During pregnancy the concentrations of many coagulation factors are increased what leads to a "physiological" hypercoagulability status and constitutes a natural protection against delivery hemorrhage. These changes may be conducive to venous thrombembolism. Antithrombin is one of the endogenous clotting inhibitors. As a serine protease, it inactivates thrombin and the efficiency of this reaction is intensified by heparin. Acquired antithrombin deficiency is caused by disseminated intravascular coagulation syndrome, deep vein thrombosis, neoplasms, nephritic syndrome, renal failure, liver diseases, long-term estrogen treatment, dialysis or extracorporeal circulation. There are also cases of inherited antithrombin deficiency which leads to thrombophilia. The following study presents a course of pregnancy and postpartum of a woman with deep vein thrombosis and acquired antithrombin deficiency as well as the applied treatment. The legitimacy of routine assay of antithrombin activity and antithrombin supplementation in pregnant women with thrombosis was considered. This procedure may be helpful when dealing with obese pregnant patients as it is difficulty to identify and establish a therapeutic dose of heparin in their cases. Therapy guidelines for pregnant patients with thrombosis and acquired antithrombin deficiency have not been established yet.
Ginekol Pol 2010 Jan
PMID:[Is venous thrombembolism during pregnancy an indication for routine assay of antithrombin activity and antithrombin supplementation?]. 2023 2

Studies in high-risk surgical patients have demonstrated the efficacy of the selective inhibitors of factor Xa and thrombin in preventing venous thromboembolism. Because of their predictable dose-response, which eliminates the need for routine laboratory monitoring, they may be more convenient for patients requiring long-term therapy, and have the potential to improve the quality of anticoagulation. The results from 2 large trials of dabigatran (a thrombin inhibitor) compared to warfarin, in patients with atrial fibrillation and those with acute symptomatic venous thromboembolism, have recently become available. These trials provide convincing evidence of the efficacy of dabigatran in preventing patient-important clinical outcomes when compared to warfarin. In this paper we critically review these trials and discuss the feasibility of replacing warfarin with dabigatran for these indications.
Pol Arch Med Wewn 2010 Apr
PMID:Dabigatran: ready for prime time? 2042 39

The occurrence of factor VIII or factor IX inhibitor following treatment of a haemophilia A or B patient with factor VIII/IX concentrates is a serious complication. In the presence of these inhibitors, bleeds cannot be treated with the missing factors. The treatment of haemophilia complicated by the presence of inhibitor has two aims. The most important aim is complete elimination of the inhibitor, and the other aim is to stop bleeding. The first aim can be achieved by regular administration of the missing factor in order to eliminate inhibitor from the patient's blood. This method is called--immune tolerance induction (ITI) The second method depends on the titer of the inhibitor, types of response and degree of bleeding. In treatment of bleeding episodes concentrates inducing thrombin generation in the plasma of patients with haemophilia complicated by inhibitor are used. This assures haemostasis, in spite of the presence of factor VIII or IX inhibitor. The concentrates used are called bypassing agents. If ITI is unsuccessful regular prophylaxis with bypassing concentrates is being introduced more and more often. According to literature this reduces the frequency of bleeds by as much as 85% and improves the quality of life of patients with severe haemophilia complicated by inhibitor.
Pol Merkur Lekarski 2011 Mar
PMID:[Prophylaxis in patients with haemophilia complicated by inhibitors]. 2154

This study investigated changes in the coagulation profile of 10 healthy female dogs subjected to ovariohysterectomy. Blood samples were collected three times--before, directly after and 24 h after surgery. Plasma samples were analyzed to determine thrombin time (TT), prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen content, D-dimer content and antithrombin (AT) III activity. The results revealed post-operative haemostatic system disorders related to prolonged APTT, higher fibrinogen and D-dimer concentrations and lower levels of AT III activity.
Pol J Vet Sci 2011
PMID:Changes in the blood coagulation profile after ovariohysterectomy in female dogs. 2172 18


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