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

The thrombolytic action of the complex heparin-ocrase on the experimentally formed fresh thrombi obtained through intravenous introduction of thrombin into an isolated length of the jugular vein was compared against the effect produced on the thrombi by equivalent amounts of individual components of the complex, i.e. heparin and ocrase. Investigations revealed a lysis of experimental fresh thrombi after intravenous injections of the complex heparin-ocrase and this lysis supervened quicker than following the action of equivalent amounts of ocrase. Heparin used in a dose equivalent to its content in the complex did, as this has been presumed, exercise no thrombolytic action at all.
 ...
PMID:[Thrombolytic action of a heparin-ocrase complex]. 65 60

The inactivation of thrombin by heat and by its physiological inhibitor, antithrombin-III, shows quite different dependence on heparin concentration. Heparin at 250 microgram/ml protects thrombin against heat inactivation, and thrombin behaves heterogeneously in this reaction. In the absence of heparin, the thermodynamic activation parameters change with temperature (deltaH+ = 733 kJ/mol and 210 kJ/mol at 50 and 58 degrees C respectively). When heparin is present, heat inactivation of the protected thrombin species proceeds with deltaH+ = 88 kJ/mol and is independent of temperature in the same range. On the other hand, heparin at 0.125-2.5 microgram/ml accelerates the thrombin-antithrombin-III reaction. Thrombin does not show heterogeneity in this reaction and the time courses at any heparin concentration and any temperature between 0 and 37 degrees C appear to follow first-order kinetics. Activation enthalpy is independent of heparin concentration or temperature, deltaH+ = 82-101 kJ/mol, varying slightly with antithrombin-III concentration and thrombin specific activity. Heparin seems to exert its effect by increasing activation entropy. On the basis of these data we suggest a mechanism of action of heparin in the thrombin-antithrombin-III reaction which accounts for all the important features of the latter and seems to unify the different hypotheses that have been advanced.
 ...
PMID:Effect of heparin on thrombin inactivation by antithrombin-III. 70 77

In vitro studies in a "mini-Kiil" dialyser showed that, in spite of presumably adequate heparinization (2.5 IU/ml plasma), 51Cr-labelled platelets and 125I-labelled fibrin(ogen) deposited on membranes and blood lines, when freshly drawn human blood was dialyzed for 30 min. Platelet retention dominated, with a Cr/I ratio 3 times that of blood. Increasing the heparin concentration led to a reduction both of 51Cr- and 125I-activity, with a slight fall in the Cr/I ratio. Heparin was unable to prevent platelet retention in the dialyser, but the platelet aggregating effect of heparin was shown to be of minor importance compared to its anticoagulant activity and effect on thrombin induced platelet aggregation. Platelet retention by the blood lines exceeded that of the dialyser, in spite of a much smaller surface area. Differences in thrombogenicity between cuprophane and silicone rubber as well as different flow characteristics in the two situations were probably contributory. When heparinized tubing was used, the radioactivity retained was negligible, but membrane radioactivity was unaltered. A considerable reduction in blood radioactivity during dialysis, not accounted for by the deposits above, suggests the additional formation of more loosely attached platelet/fibrin(ogen) masses.
 ...
PMID:Thrombus formation in the artificial kidney. Platelet and fibrin(ogen) content of experimental thrombi detected by radioisotope technique. 72 47

About 80% of thrombin was inactivated after 50 minutes chemical reduction at 22 degrees C in a reaction mixture containing o.1 M mercaptoethanol and 2.6 M urea. The reduced protein was spontaneously reoxidated in air at 22 degrees C in 30--60 minutes. The reoxidation of disulphide bonds in thrombin led to partial reactivation of the enzyme. Recovery of thrombin activity after oxidation ranged from 0 to 60% according to the conditions of reoxidation in air. Heparin and copper ion increased the rate of reactivation, whereas in the presence of 10 mM iodoacetamide there was no reactivation.
 ...
PMID:Air reoxidation and reactivation of reduced thrombin. 75 45

A method of heparinless, oxygenatorless, left heart bypass perfusion rewarming following surface hypothermia, with the use of a closed circuit with 130 ml. prime volume including heat exchanger, has been devised. The use of polyurethane-polyvinyl-graphite (PPG)-coated tubing has previously been reported. In this text, the use of an athrombogenic coating with cetyl-pyridinium chloride (CPC) as a regional heparin carrier was studied in dogs, comparing groups with PPG tubing and total systemic heparinization or plain polyvinyl tubing without systemic heparinization. Heparin compounded in the CPC coating eluted into the blood and caused mild transient whole-body heparinization during rewarming from 20 degrees to 25 degrees C., as evidenced by prolongation of the thrombin time. Alterations of hematologic parameters in all three groups were similar to those during surface rewarming except for those affected by heparinization. The left heart bypass method was found useful for hypothermic open-heart surgery when utilized with an athrombogenic surface coating or total body heparinization. It was concluded that the CPC coating is superior to the PPG coating since no cracking surface develops, it is translucent, and it provides a more effective athrombogenic surface.
 ...
PMID:Use of athrombogenic tubing for perfusion rewarming following surface-induced deep hypothermia. 76 68

Heparin activity was assessed in 11 patients who underwent extracorporeal circulation for open-heart surgery. The activated partial thromboplastin time (A-PTT), thrombin time, protamine sulphate titration and factor Xa inhibition assay were used. The patients received heparin 3 mg/kg body weight, and 20 mg/450 ml blood was added to the pump. When the operative procedure was extended beyond 100 minutes patients received an additional 1,5 mg heparin/kg body weight. Protamine sulphate in a dose of 1,5 mg/1 mg heparin, was given to neutralize the heparin activity. The A-PTT was the easiest test which gave reliable results. The factor Xa inhibition assay measured heparin levels most precisely and mirrored the A-PTT results in all but one instance. These results indicate that the protocol employed produced adequate anticoagulation for the bypass procedure in all the patients. Protamine sulphate failed to neutralize heparin adequately after bypass in the 3 patients who received additional heparin during the surgical procedure. The monitoring of heparin activity during and after extracorporeal circulation is a desirable addition to open-heart surgical treatment.
 ...
PMID:The monitoring of heparin activity during extracorporeal circulation. 88 33

Calcium ions induce retraction of reptilase clots. This could also be induced by thrombin. Heparin inhibited the reptilase clot retraction induced either by thrombin or calcium, but did not influence the clot retraction induced by ADP. This indicated that the clot retraction induced by Ca2+ was mediated by an activation of the coagulation system with the formation of thrombin.
 ...
PMID:Mechanism of calcium-induced reptilase clot retraction. 93 9

Heparin (100 U/kg bodyweight) was administered as single i.v. injections, and heparin concentration in plasma determined by polybrene titration. Mean concentration half-life was 74.7 min in the normal group (n = 6), 118.6 min in the nephrectomized patients (n = 5), and 97.8 min in the other uraemic patients (n = 6). The differences between the mean values for the normals and for the 2 patient groups were statistically significant (p is less than 0.001 and p approximately 0.2 respectively). Mean anticoagulant half-life (based on thrombin clotting time) was 64.3, 75.8 and 62.7 min in the 3 groups. The differences between heparin concentration half-life and anticoagulant half-life in the 3 groups were statistically significant. These differences may be partly explained by a significant fall in heparin cofactor activity after injection of heparin. There was a strong positive individual correlation between heparin concentration half-life and anticoagulant half-life in the patients (r = 0.94), but not in the normal group (r = 0.31). There was a strong negative individual correlation between heparin tolerance and heparin concentration half-life in the patients (r = -0.84), but no correlation in the normal group. It is concluded that severely impaired renal function has a significant, but moderate influence on heparin elimination.
 ...
PMID:Heparin elimination in uraemic patients on Haemodialysis. 95 71

The coagulation and fibrinolytic systems play a key role in maintaining the integrity and patency of the vascular compartment. Pregnancy induces extensive physiological changes in these systems, thus creating an enhanced capacity to produce fibrin and a diminished ability to remove it. Fibrin deposition localized to the uteroplacental circulation is a feature of normal pregnancy. In women with fatal eclampsia, disseminated intravascular coagulation with fibrin deposition in the renal glomeruli is well documented. The condition of preeclampsia is not well defined. Nonetheless, evidence of intravascular coagulation, as shown by elevated levels of fibrin degradation products and reduced platelet counts, has been found in many women with preeclampsia. Serial studies showed that thrombin generation, as indicated by the ratio of factor VIII-related antigen to factor VIII coagulant activity, is considerably in excess of that which occurs in normal pregnancy, and its appearance coincides with the development of the clinical features of preeclampsia. Heparin therapy has bot been proven of value in established preeclampsia, but this fact does not disprove that role that intravascular coagulation may play in the pathogenesis of the disease. A controlled trial ina high-risk group of low-dose he;arin and an antiplatelet agent from the 16th to the 18th weeks of pregnancy onwards is required to elucidate the role of intravascular coagulation in preeclapmsia and its effect on the fetus.
 ...
PMID:The role of coagulation and fibrinolysis in preeclampsia. 100 56

Eighteen patients were given carefully controlled intravenous heparin for thromboembolic disease of pregnancy. Thirteen were treated in later gestation and postparium, mainly following warfin therapy. One was treated in early pregnancy and 4 in the postpartum period. Heparin was delivered by constant infusion and dosage regulated by maintaining the thrombin time at 2 to/ times normal. Therapy was stopped for a few hours before and after delivery so that the thrombin time was normal or nearly normal at birth. Two minor episodes of thrombosis recurred in 1 patient while on warfarin, and significant postpartum bleeding occurred in one other. Substituting heparin for warfarin in late gestation was of value in preventing neonatal bleeding complications.
 ...
PMID:Thromboembolism in pregnancy. 107 85


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