Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A hundred and eighty three patients with a primary myocardial infarction less than 4 hours old were included in a double blind trial versus placebo comparing an isolated plasminogen streptokinase activator complex (APSAC: 30 mu in 5 mn) and tissue type plasminogen activator (rt PA: 10 mg bolus followed by 90 mg in 130 mn). Clinical evolution, side effects, patency of the artery responsible for infarction, left ventricular contractile function (contrast angiography on the 7th day and angioscintigraphy on the 21st day) and infarct size were studied. The two groups were comparable in age (54 +/- 11 years), delay in randomisation (170 +/- 50 mn), infarct site and severity of cardiac failure. There was no significant difference in hospital mortality (7 in the rt PA group and 5 in the APSAC group) or in adverse effects (haemorrhage: rt PA: 9 patients, APSAC: 11 patients). The patency was 72% in the APSAC and 76% in the rt PA group. Left ventricular function and infarct size were comparable in the two groups: angiographic EF (0.50 +/- 0.1 in the APSAC and 0.52 +/- 0.1 in the rt PA group: NS); asynergic score (11.3 +/- 1.7 in the APSAC and 10.5 +/- 1.8 in the rt PA group: NS); infarct size (10.9 +/- 8.0 in the APSAC and 9.4 +/- 7.2 in the rt PA group: NS). This trial shows that these two thrombolytic agents have the same efficacy. The authors recommend adaptation of the dosage of rt PA to body weight.
Arch Mal Coeur Vaiss 1992 Nov
PMID:[Study of new thrombolytic agents in myocardial infarction: a multicenter randomized trial (APSAC versus rt-PA)]. 130 Sep 57

The nitrate derivatives in clinical usage have in vitro platelet inhibitor and therefore antiaggregant properties. As with EDRF, this effect is mediated, at least partially, by increased intraplatelet cGMP concentrations. There is a probable synergistic action with prostacyclin and its clinically stable analogues which exert their inhibitor effect via cGMP. The reality of an ex vivo inhibitor effect (after clinical administration) is more difficult to demonstrate. Some groups have reported prolonged bleeding times after administration of trinitrin. The interactions of nitrate derivatives with molecules used as platelet inhibitors, such as aspirin, require further study as do interactions with heparin (possible induction of resistance by a qualitative anti-thrombin III deficiency) and thrombolytics (increased clearance of tissue type plasminogen activator).
Arch Mal Coeur Vaiss 1992 Apr
PMID:[Nitrate derivatives and hemostasis: fundamental concepts and clinical implications]. 153 Apr 30

One hundred patients admitted to a centre of interventional cardiology with acute myocardial infarction of less than 6 hours, underwent coronary angioplasty of first intention because of contra-indications to thrombolytic therapy (n = 20) or after thrombolytic therapy with streptokinase (n = 54), acylenzymes (n = 12) or tissue type plasminogen activator (n = 14). The indication of angioplasty were those of the TIMI (Thrombolysis in Myocardial Infarction) classification (occluded artery, TIMI grade 0) (n = 60) (suboccluded artery, TIMI grade 1) (n = 40). The criterion of success of angioplasty was an increase greater than 1 of TIMI grade. Reperfusion of the coronary artery was obtained by angioplasty in 95% of failures of thrombolysis and in 90% of patients with contra-indications to thrombolytic therapy. The early reocclusion rate at D1 was 2%. Repeat angioplasty at D1 was successful in both these cases and the arteries were still patent at D21. The reocclusion rate at the third week in 75 patients who underwent control coronary angiography was 5.3%. In patients with arterial occlusion, immediate angioplasty attained two objectives in the same procedure: a high rate of emergency myocardial reperfusion and a low rate of reocclusion. The average left ventricular ejection fraction (all arteries) significantly improved (+9.2% in absolute values) when the artery remained patent (p less than 0.001), especially when the initial ejection fraction was low. In the patients who had occluded arteries at control angiography at 3 weeks, the ejection fraction decreased (-4% in absolute values) (NS). The following complications were observed: 4 coronary artery dissections and haematomas at the site of femoral puncture in patients who had received thrombolytic therapy (10 drained surgically). The hospital mortality was 3% and global mortality after an average follow-up period of 19.6 months was 5%. Coronary angioplasty in acute myocardial infarction carries a low risk and seems to be beneficial in patients with contra-indications to or failure of thrombolysis.
Arch Mal Coeur Vaiss 1991 Apr
PMID:[Acute myocardial infarction: immediate coronary angioplasty for failure or contra-indications of thrombolytic therapy. Apropos of a series of 100 cases]. 190 14

Anistreplase is a second generation thrombolytic agent, an equimolecular streptokinase lys-plasminogen complex the active site of which is temporarily blocked by a p-anisoyle group. Acylation enables the drug to be administered as a bolus intravenous injection over 2 to 5 minutes, and it protects anistreplase against circulating inhibitors, hence a plasma elimination half-life of 90 minutes. Deacylation is slow and progressive (deacylation half-life: 105 minutes), and it begins as soon as the product is injected. It reduces the hypotensive effect of streptokinase, permits a prolonged action in the thrombus and limits the risk of reocclusion. Using lys-plasminogen increases the affinity of the drug for fibrin and potentiates its accumulation and retention in the thrombus. In vitro studies have shown that the affinity of anistreplase for fibrin is similar to that of t-PA. In doses used for myocardial infarction, anistreplase induces a pronounced fibrinogenolysis. The effectiveness of the drug has been demonstrated on numerous animal models and subsequently by clinical trials.
Arch Mal Coeur Vaiss 1990 Feb
PMID:[Anistreplase. Pharmacology and biological data]. 210 41

Forty six patients admitted for precordial chest pain were included in this study. The clinical, electrocardiographic, enzymatic and angiographic features allowed retrospective identification of 6 subgroups (nos 1 to 6): all transmural myocardial infarction (Q-MI) (Group 1), Q-MI without intracoronary thrombus (Group 2), Q-MI with intracoronary thrombus (Group 3), acute non-Q wave infarction (non Q-MI) (Group 4), unstable angina (Group 5) and atypical chest pain (Group 6). Several blood clotting factors were studied; von Willebrand factor (VWF), fibrinogen, tissue plasminogen activator (t-PA) and its inhibitor (PAI-1) and factor VII. There was no significant difference in the fibrinogen, t-PA, PAI-1 or factor VII levels between the 6 groups. On the other hand, the VWF was increased in the all transmural myocardial infarction (Q-MI) groups (n. 1). In Group 3 with visible intracoronary thrombus the VWF was high or very high in all patients, attaining three times the normal values. The values were lower in Group 5 (unstable angina) patients in whom no thrombus was observed on coronary angiography. The differences between Group 1 and Groups 4, 5 and 6 were statistically significant (p less than 0.05). The VWF was higher in the Q-MI group with intracoronary thrombus than in the group without thrombus, but the difference was not statistically different. In conclusion, the VWF may be considered to be a marker for thrombus and/or endothelial activation but a larger study population would be required to identify more accurately the subgroups with thrombosis or risk of thrombosis.
Arch Mal Coeur Vaiss 1989 Nov
PMID:[Relation of an increase of von Willebrand factor in the blood, acute myocardial infarction, unstable angina and coronary thrombosis]. 251 33

The effect of a low molecular weight heparin CY 222 (Choay) on t-PA induced thrombolysis was investigated in the rabbit jugular thrombosis model. The compound CY 222 was administered as 1.4 mg/kg (group A) by IV injection immediately after start of t-PA infusion (0.125 and 0.250 mg/kg) and then hourly during the 4 hours of infusion of the thrombolytic; results were compared with those obtained in the absence of CY 222 (group B). A significant increase in percent thrombolysis was noted in the presence of CY 222: A versus B = 31 +/- 1/22 +/- 2 (p less than 0.02) (tPA = 0.125 mg/kg; 72 +/- 4/36 +/- 3 (p less than 0.01) (tPA = 0.250 mg/kg). Anti-Xa activity 60 minutes after 1.2 u/ml IV of CY 222 was comparable with that observed in patients with venous thrombosis treated with high-dose CY 222. The conclusion is reached of the interest of CY 222 in combination with t-PA, the CY 222 acting not only on coagulation by also on thrombolysis by potentiating the effect of t-PA.
J Mal Vasc 1987
PMID:[Low molecular weight heparin CY 222 (Choay) potentiates the thrombolytic effect of 1-PA in rabbits with experimental thrombosis of the jugular vein]. 283 93

Fibrinolysis is a physiological process which aims at dissolving intravascular thrombi and is mediated by activation of plasminogen to plasmin. Streptokinase (SK) and urokinase (UK) are non-specific plasminogen activators. They have proved effective as thrombolytic agents, but their use is limited by the risk of haemorrhages due to systemic fibrinogenolysis. More fibrin-specific drugs have recently been developed. One is a tissue plasminogen activator (t-PA), the other is a urokinase precursor (pro-UK), also called single chain urokinase plasminogen activator (scu-PA). Genetic engineering techniques have resulted in the large-scale production of a "recombinant t-PA" (rt-PA) and a "recombinant scu-PA" (r scu-PA) for therapeutic use, notably in acute myocardial infarction. In vitro, these two drugs exhibit a thrombolytic activity that is equal to, or greater than that of SK or UK. In vivo, their fibrinogenolytic effect is less pronounced, and their thrombolytic effect greater than those of SK or UK. "Acyl-enzymes" have more recently emerged. These are inactive acylated SK-plasminogen complexes which progressively become effective in plasma after deacylation. So far, the most extensively studied of these complexes is BRL 26921 (anisoylated plasminogen streptokinase activator complex, or APSAC) which is administered by bolus intravenous injection. It is more thrombolytic than SK but produces systemic fibrinogenolysis to an equivalent degree. Injected intravenously (by infusion or bolus) during the first hours of a coronary infarction these three new thrombolytic agents have proved effective in promoting coronary reperfusion, with an early coronary patency rate of 70-75%.(ABSTRACT TRUNCATED AT 250 WORDS)
Arch Mal Coeur Vaiss 1987 Nov
PMID:[New thrombolytic agents in myocardial infarction]. 312 22

Some molecular defects of components of the coagulation or fibrinolytic system are associated with thromboembolism. One possibility is that physiologic inhibitors of the coagulation system have an abnormal function e.g. protein C, protein S, antithrombin III and cofactor II of heparin. Also a hindered activation of the fibrinolytic system may predispose to thrombosis; the impaired activation may be due to deficient synthesis and/or release of tissue-plasminogen activator, an increased level of its inhibitor or a functional defect of the plasminogen molecule. A few cases of congenital dysfibrinogenemia have been described in which the functional defects of the molecule are held responsible for recurrent thrombosis. An acquired thrombotic disorder is due to the presence of immunoglobulins which prolongs phospholipid-dependent coagulation by binding to epitopes of some phospholipids. This so-called lupus anticoagulant was originally described in patients with systemic lupus erythematosus but is a misnomer as it is more frequently encountered in patients without lupus.
J Mal Vasc 1987
PMID:[Molecular defects of coagulation factors and of the fibrinolytic system associated with thromboembolism]. 354 55

Four years after a triple valve replacement, a 51 year old woman presented with signs of thrombosis of her tricuspid Saint Jude valve prosthesis, confirmed at echocardiography and fluoroscopy. Treatment with tissue-type plasminogen activator was completely successful with a result which was sustained at 18 months. A review of the literature confirms the superiority of thrombolytic therapy of first intention in the treatment of thrombosis of tricuspid mechanical prosthetic valves.
Arch Mal Coeur Vaiss 1994 Jun
PMID:[Thrombosis of mechanical tricuspid valve prosthesis: treatment by tissue-type plasminogen activator. Success after a 18 month-follow-up]. 770 26

From July 1990 to July 1993, we performed 41 percutaneous intra-arterial thrombolysis procedures for the treatment of obstructed infra-inguinal bypass grafts in 32 patients. There were 27 men and five women with a mean age of 63 +/- 17 years (range 21 to 83 years). The symptoms of occlusion were intermittent claudication in three cases, rest pain in 12 cases, severe ischemia without sensitive-motor loss in 26 cases. Bypasses were achieved using a prosthesis in 18 cases (43.9%), a saphenous vein in 10 cases (24.4%), an arterial allograft in nine cases (21.9%), and a composite prosthesis-vein graft in four cases (9.8%) (table I). The distal anastomosis of the bypass graft was located on the popliteal artery in 26 cases (63.4%) and a crural artery in 15 cases (36.6%). The mean duration of the occlusion was 4.9 +/- 3.4 days (range 1 to 15 days). The percutaneous approach was through the contralateral common femoral artery in 26 cases (63.4%), through the ipsilateral common femoral artery in seven cases (17.1%), through the left humeral artery in eight cases (19.5%). In all cases the thrombolytic agent was the recombinant tissue-type plasminogen activator (rt-PA). Each procedure began with the injection of a five milligram bolus of rt-PA into or onto the thrombus followed by infusion of rt-PA into the thrombus at a dose of 0.05 mg/kg/h. Intravenous heparin was simultaneously administered. Serum fibrinogen, prothrombin time, and partial thromboplastin time (PTT) were measured every three hours.(ABSTRACT TRUNCATED AT 250 WORDS)
J Mal Vasc 1994
PMID:[Intra-arterial thrombolysis using rt-PA for the treatment of occluded infra-inguinal bypasses]. 807 60


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