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

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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)

A new method is presented for estimating the activator (plasminogen-streptokinase complex) concentration in native plasma of patients undergoing streptokinase infusion. The principle of the method is based on clot lysis time as recorded by the thromboelastograph. The test clot constituents were bovine fibrinogen, bovine plasminogen, EDTA, human plasma (with unknown activator concentrations), and thrombin. In order to obtain a standardization line, urokinase dissolved in NaCl solution was substituted for patients' plasma. Thus, each lysis time could easily be converted into urokinase equivalent (CTA-u/ml). Streptokinase and plasminogen molecules in undiluted patients' plasma were found to exist both in an activator-bound (equimolar plasminogen-streptokinase complex) and in a freely circulating form. This result is in agreement with earlier findings where the activator complex was demonstrated to be a widely dissociated complex in highly diluted plasma of patients, thus displaying an ample proportion of free streptokinase and plasminogen and molecules. Streptokinase treatment using dosage schemes of 100,000 u SK/h, and 200,000 u/h were monitored by quantitative activator, streptokinase, and plasminogen measurements. An average activator concentration of 50-100 CTA-u/ml and a SK-concentration of 7-16 u/ml were recorded during streptokinase infusion. Plasminogen values averaged 0.25%, independent of the amount of streptokinase infused. Each drop in streptokinase was accompanied by a drop in activator during the infusion, and each rise in streptokinase by a rise in activator. There was a strong correlation between streptokinase and activator concentrations in that, on the average, 1 u streptokinase equalled 8.4 CTA-u/ml activator (correlation coefficient r = 0.9) It is concluded that the activator concentration in the plasma of patients undergoing fibrinolytic treatment can easily be adjusted by regulating the hourly streptokinase influx.
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PMID:Studies on activator formation in human plasma with streptokinase. III. Investigation of activator kinetics in undiluted plasma in terms of urokinase equivalents. 13 62

Plasma fibrinopeptide B (Bbeta1-14 or FPB) immunoreactivity was studied by radioimmunoassay in patients who received intrauterine infusion of hypertonic saline to terminate pregnancy. FPB immunoreactivity increased with thrombin treatment (TIFPB) suggesting the presence of a larger FPB-containing peptide, since purified FPB is not altered by thrombin, whereas thrombin increases the immunoreactivity of Bbeta1-42 (which includes FPB) 10-fold. TIFPB immunoreactivity in plasma, drawn 4 h after hypertonic saline infusion eluted from Sephadex G-50 similarly to isolated Bbeta1-42. Streptokinase, incubated with normal plasma progressively generated TIFPB immunoreactivity, which showed a major component which eluted from Sephadex G-50 similarly to Bbeta1-42. Streptokinase generated TIFPB much more rapidly in reptilase-treated plasma that contains fibrin I, (which still includes FPB), indicating that fibrin I is preferred over fibrinogen as a substrate for plasmin cleavage of arginine (Bbeta42)-alanine (Bbeta43). Serial studies were then made in 10 patients receiving intrauterine hypertonic saline. Fibrinopeptide A (FPA) levels rose immediately, reached a peak between 1 and 2 h, were declining at 4 h, and were normal at 24 and 48 h. TIFPB levels rose slightly in the 1st h, reached a peak at 4 h, and had returned to base-line values at 24 h. Serum fibrinogen degradation product levels were unchanged at 1 h, reached their highest level at 4 h, and were still markedly elevated at 24 and 48 h. Fibrinogen levels dropped slightly being lowest at 4 and 24 h. Platelet counts declined in parallel with the fibrinogen levels over the first 4 h, but continued to decrease through 48 h. Beta thromboglobulin (betaTG) levels generally paralleled FPA levels whereas platelet factor 4 (PF4) levels showed only slight changes. The data indicate that immediately after intrauterine hypertonic saline infusion thrombin is formed that cleaves FPA from fibrinogen to produce fibrin I and releases betaTG and PF4 from platelets. Later plasmin cleaves Bbeta1-42 from fibrin I to produce fragment X, which is further degraded to form serum fibrinogen degradation products. This sequence of proteolysis indicates that plasmin action on fibrin I serves as a mechanism that regulates fibrin II formation by removing the Bbeta chain cleavage site, which is required for thrombin action in converting fibrin I to fibrin II.
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PMID:Sequence of fibrinogen proteolysis and platelet release after intrauterine infusion of hypertonic saline. 50 Aug 18

A method of a quantitative determination of plasma streptokinase concentrations in patients undergoing streptokinase infusion is described. The principle of this method is based on the clot lysis time recorded by the thromboelastograph. The test clot constituents were bovine fibrin, bovine plasminogen, human euglobulin, EDTA, human plasma (of unknown streptokinase quantity) and thrombin. As rather high concentrations (fixed excess) of plasminogen (euglobulin) and fibrinogen were present in the test coagulum, no interference with changing plasminogen and fibrinogen levels of the patient's plasma was observed. Furthermore, due to high EDTA concentrations, no interaction with platelet functions and coagulation factors took place. The standard deviation in measuring 2 u streptokinase in 1 ml human plasma was determined as s = +/- 0.19 u/ml, of 5 u streptokinase at s = +/- 0.47 u/ml and of 20 u streptokinase at s = +/- 2.5 u in 1 ml of human plasma. Plasma samples of patients undergoing fibrinolytic treatment were investigated with regard to their streptokinase content. Streptokinase concentration values varied between 0.7 u and 15 u/ml plasma. The average half life of streptokinase in the organism was 18 min. The decay of streptokinase in plasma at different temperatures and over various periods of time was also determined. A considerable loss of streptokinase in the plasma during storage at room temperature could be observed. Therefore, the determination procedures should be carried out without delay.
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PMID:[The technique of quantitative determination of streptokinase in the patient's plasma (author's transl)]. 81 26

In 17 unaesthetized dogs several side branches of the left descending coronary artery were ligated. The ST-segment elevation in the epicardial ECG ascended to 22 mV after 5 min and to 19 mV after 20 min. Aortic pressure, left ventricular enddiastolic pressure, heart rate and hemostasiological parameters (thrombin-time, thrombin-coagulase-time, reptilase-time, plasma-fibrinogen, staphylococcal clumping test) did not change significantly. 20 min after the beginning of coronary occlusion, the vessels were reopened. When ST-segment elevation had disappeared, a controlled fibrinolytic therapy (Streptokinase 1.5 Mega I.E. in 30 min, later on 0.75 Mega I.E./h) was induced. When an effective fibrinolysis could be demonstrated by the hemostasiological parameters, the same vessels were occluded again. Now the hemodynamic parameters too did not change significantly, but the ST-segment elevation was significantly diminished for more than 50% compared with simple ligation. A control group, which only got the solvent of the streptokinase, showed the same ST-segment elevation. This effect, induced by streptokinase is ascribed to fibrinogen degradation products and a diminution in the amount of fibrinogen which cause an improvement of microcirculation.
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PMID:[Influence of a streptokinase-induced fibrinolysis on the extent of the acute experimental myocardial infarction (author's transl)]. 116 21

The effects of thrombolytic therapy in acute myocardial infarction are related exclusively to coronary arterial reperfusion. This is the main factor which influences myocardial salvage, the conservation of left ventricular function and, ultimately, the reduction in mortality. From the beginning of the 80s, the patency (or reperfusion) rate was arbitrarily assesses at 90 minutes. However, arterial reperfusion is a progressive phenomenon and the patency rate in a population of acute myocardial infarctions varies with time. Depending on the thrombolytic agent and the rate of administration, the patency increases at a variable rate attaining a plateau at the 4th-6th hour, the maximal patency being obtained between the 24th to the 48th hour. Therefore, assessing patency at the 90th minute of thrombolytic therapy is an approximate and relatively inaccurate method of assessing the efficacy of a given thrombolytic agent. When evaluating a thrombolytic drug administered at a certain dosage, the rate of reperfusion and the value and precocity of the plateau phase must be taken into account. The respective performances of different thrombolytics in terms of arterial patency are comparable. Nevertheless, the rate of reperfusion with Streptokinase given at the dose of 1.5 million i.v. in 60 minutes is lower than that obtained with more recent thrombolytic drugs. Streptokinase also appears to be less active on chronic thrombi. The late patency rate after the 24th hour is over 90% with nearly all thrombolytic drugs but it would seem to be less with rt-PA because of a higher reocclusion rate associated with this particular agent. The study of reocclusion requires control coronary angiography between the 24th and 72nd hour (7th day in some studies). The prevalence of this complication is influenced by several factors, especially the severity of residual stenosis after thrombolysis and the grade of perfusion obtained after the treatment: secondary reocclusion is significantly lower with long-acting and non-fibrin specific thrombolytic agents. It is approximately 2 to 5% with APSAC, Streptokinase and pro-urokinase, and two to three times greater with rt-PA. Finally, the use of more powerful antiplatelet drugs than those currently available and of specific anti-thrombin agents could reduce the rate of secondary reocclusion. Associations of thrombolytic agents, the development of thrombolytic chimera and new thrombolytic molecules could improve the efficacy of thrombolytic therapy in terms of capacity of reperfusion and tolerance, especially with respect to haemorrhagic complications.
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PMID:[Arterial permeability, objective of thrombolytic therapy]. 153 Apr 9

In this study, we have evaluated the effects of four different thrombolytic agents, including Streptokinase from Hoechst and from Kabivitrum, Urokinase from Abbott and tissue plasminogen activator (t-PA) from Genetech, on platelet-rich plasma clots and platelet aggregation. At concentrations lower than 50 ugs/ml, t-PA had no inhibitory effect on clot retraction or platelet aggregation induced by weak or potent agonist. At a higher concentration (greater than 100 ugs/ml), t-PA specifically antagonized the action of thrombin on clot formation and platelet aggregation. Streptokinase (Kabivitrum) potentiated the action of weak agonists on platelet aggregation, but the same agent from Hoechst had no negative or positive influence. None of the drugs tested had an adverse effect on platelet function at suggested therapeutic levels. None of the thrombolytic agents were capable of dissociating preformed clots made from platelet-rich plasma. However, all of them caused lysis of whole blood clots. Also, prior incubation of plasma alone or platelet-rich plasma with any of the agents prevented subsequent clot formation. The studies demonstrate that thrombolytic drugs at therapeutic concentrations do not affect platelet function adversely. They have a potent effect on whole blood clots, but not on clots from platelet-rich plasma. Therefore, platelets may play a critical role in determining the degree of reperfusion and the frequency of reocclusion following treatment with thrombolytic agents in vivo.
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PMID:Influence of thrombolytic agents on human platelet function. 186 14

In an experimental animal model of femoral artery thrombosis, contrast angiography was compared to intravascular angioscopy. Additionally, the effect of mechanical, rotational thrombectomy and the additive benefit of the administration of intravascular streptokinase were assessed by means of both procedures. After external forceps crush injury alone, contrast angiograms were generally normal (6 of 14) or showed minimal luminal irregularity (3 of 14), and 5 of 14 had 30% to 50% stenosis. With angioscopy, none appeared normal, and 14 of 14 showed thrombi layered along the wall, as well as intimal flaps, and 6 of 14 had partially occlusive thrombi (p less than 0.001 angiography vs angioscopy). After 2-hour occlusion and injection of thrombin into the injured segment, angiographic total (5 of 14), subtotal (3 of 14), or partial thrombotic occlusions (5 of 14) were created. Angioscopy showed similar results, except that total occlusions were classed as subtotal occlusions. After rotational thrombectomy, most arteries again appeared normal by contrast angiography (6 of 11) but none were angioscopically normal (p less than 0.006). Streptokinase, administered after rotational thrombectomy in seven arteries, normalized one 30% angiographic stenosis; there were no other angiographic changes. Findings with angioscopy were also unchanged. We conclude that in the diagnosis and treatment of intravascular thrombosis, angioscopy is generally more sensitive in the detection of intravascular thrombi, with the exception of total thrombotic occlusions. Angioscopy was uniquely effective in identifying subintimal flaps, which were never identified by angiography. In this model, streptokinase provided little or no additional thrombolytic benefit to mechanical thrombectomy alone.
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PMID:Combined mechanical and chemical thrombolysis in an experimental animal model: evaluation by angiography and angioscopy. 229 76

Despite increasing success with low-dose intra-arterial thrombolysis, early rethrombosis still occurs. Platelet aggregation is thought to play a major part in this process. We have therefore investigated the effects of recombinant tissue plasminogen activator (rt-PA) and streptokinase on platelet function at doses currently used for peripheral arterial thrombolysis. Platelet-rich plasma was stirred at 37 degrees C, with either streptokinase (100, 300 or 1000 units ml-1) or rt-PA (10 (T10), 30 (T30) and 100 (T100) mg l-1), with immediate addition of an agonist for platelet aggregation (thrombin, collagen, adenosine diphosphate (ADP) or adrenaline) at a predetermined threshold dose. Significant inhibition of collagen-induced and adrenaline-induced platelet aggregation was produced with rt-PA at all doses used (P less than 0.05). With adrenaline as the agonist, T100 produced disaggregation to a mean (s.d.) level of 26 per cent. Thrombin-stimulated platelet aggregation was significantly reduced by T100 (P less than 0.001) and T30 (P less than 0.01) only, disaggregation being dose-dependent and complete with T100. Using ADP as the agonist, T100 produced a significant reduction in maximum platelet aggregation (P less than 0.01), and disaggregation was achieved to a mean (s.d.) level of 48(13) per cent. Streptokinase did not produce any significant changes in any parameter of aggregation.
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PMID:Differential effects of low-dose tissue plasminogen activator and streptokinase on platelet aggregation. 251 82

To evaluate efficacy and tolerability of the systemic infusion of 1,500,000 streptokinase units in 30', we treated 26 consecutive patients with acute myocardial infarction within 3 hours of the onset of chest pain. They were 23 men and 3 women, mean age was 59 +/- 8 years. None of them had a history of previous myocardial infarction. From clinical and electrocardiographic data, as well as from creatine kinase curves, we assumed myocardial reperfusion in 19 patients (73%). Within 30' after infusion, thrombin time increased to more than 300" in 25/26 patients (96%). Streptokinase induced hypotension (which we defined as a decrease in systolic blood pressure of more than 30 mmHg) in 13 patients (50%), and in 5 of them (19%) systolic blood pressure fell below 90 mmHg. Hypotension was counteracted by adopting the Trendelenburg position in 7 patients, and by an intravenous infusion of atropine in 5. In the remaining patient, streptokinase infusion was slowed down. Due to these interventions, a non-significant decrease in systolic blood pressure was observed from 129 +/- 26 to 112 +/- 20 mmHg at the end of the infusion. Streptokinase-induced hypotension was not predicted either by clinical, or electrocardiographic, or chest X-ray film data, or laboratory findings. No other side-effects occurred. Hence, the infusion of 1,500,000 streptokinase units in 30' in the acute phase of myocardial infarction is active, and well tolerated. It must be emphasized, however, that during the infusion, hypotension occurs frequently and unpredictably, sometimes reaching alarm levels. This makes the monitoring of systolic blood pressure imperative during streptokinase infusion.
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PMID:[On the possibility of accelerating thrombolytic therapy in the acute phase of myocardial infarction: efficacy of and tolerance to the infusion of 1.5 million units of streptokinase in 30 minutes]. 274 15

We have studied the effect of streptokinase on platelets in platelet-rich plasma (PRP) and of plasmin on washed platelets. By three and one-half minutes after the addition of 50,000 IU/mL streptokinase to PRP, the maximum rate of ristocetin-induced platelet agglutination declined 40%, and by 60 minutes, it declined 70%. During the same time interval, the thrombin time increased from 20 seconds to over 120 seconds. At a concentration as low as 50 IU/mL, streptokinase reduced the maximum rate of ristocetin-induced platelet agglutination by 50% and prolonged the thrombin time to 1.5 times control value. Streptokinase added to PRP also caused inhibition of platelet aggregation following stimulation by 2.9 mumol/L adenosine diphosphate, 0.25 U/mL thrombin, and 0.025 mg/mL collagen. Plasmin, 0.05 to 1.0 CU/mL, reduced ristocetin-mediated agglutination of washed platelets in the presence of von Willebrand factor (vWF) from 66% of control to 2% of control, following a one-hour incubation. Autoradiograms produced following sodium dodecyl-polyacrylamide gel electrophoresis (SDS-PAGE) of plasmin-treated 125I-surface-labeled platelets demonstrated progressive loss of a protein with a molecular weight (mol wt) of 180,000; simultaneously, a protein with mol wt 135,000 appeared on autoradiograms produced following SDS-PAGE of the surrounding platelet medium. These proteins are similar in molecular weight to glycoprotein (gp) Ib, a platelet surface receptor for vWF, and glycocalicin, a proteolytic fragment of gpIb. By use of an enzyme-linked immunosorbent assay (ELISA) based immunoinhibition assay for glycocalicin, we were able to demonstrate that plasmin treatment of washed platelets released a glycocalicin-related antigen into the surrounding medium and that appearance of this material corresponding to loss of vWF-dependent, ristocetin-induced agglutination.
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PMID:Plasmin effect on platelet glycoprotein Ib-von Willebrand factor interactions. 315 89


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