Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.73 (urokinase-type plasminogen activator)
 10,685 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A group of 37 patients with myocardial infarction less than 6 hours old was given 5,000 IU of heparin and 0.75 mg/kg of tissue plasminogen activator (rt-PA) (Group A, N = 18) or placebo (Group B, N = 19) intravenously over 90 minutes in a double blind study. Blood sampling was performed before, during and after treatment. The plasma rt-PA concentrations (micrograms/ml) of Group A were as follows: (Table: see text) The concentrations of plasminogen and antiplasmin have decreased significantly as did the fibrinogen level: a concentration of 1 g/l was observed in 7 cases during rt-PA therapy, lasting for 4 to 8 hours after the end of the infusion of rt-PA in 3 cases. The increase of FDP during rt-PA (m = 551 and 222 micrograms/ml at the 60th and 90th minutes) was relatively moderate considering the average level of defibrination (61%). No significant biological changes were observed in Group B. These results support those of our in vitro trials: at comparable thrombolytic activities, the reduction of plasma fibrinogen is less with rt-PA than with streptokinase (SK) or urokinase (UK). However, at concentrations 1 microgram/ml, rt-PA causes almost complete defibrination.
Arch Mal Coeur Vaiss 1986 Oct
PMID:[Tissue plasminogen activator (t-PA) in myocardial infarction. Biological aspects]. 310 72

The prourokinase-urokinase system physiologically contributes to fibrinolysis activation. It is therefore rational to envisage the use of urokinase in thrombotic diseases, and notably in the acute phase of myocardial infarction (MI) where coronary thrombosis is virtually constant. The main studies on this subject were published in 1975 and in 1985, thus reflecting the changes in therapeutic concepts that have occurred during these 10 years. The older studies concerned patients who were admitted within the first 12 hours of MI and had no early angiographic examination; the results were evaluated indirectly on clinical and enzymatic criteria and on the regression of electrical signs of myocardial suffering. The more recent studies concern patients who are treated at an early stage, often within the first 3 hours of the accident, on the basis of experimental data which favoured early coronary reperfusion as a means of protecting the myocardium; in these studies coronary arteriography is performed immediately after the thrombolytic treatment; computer-assisted studies of the left ventricular function are also carried out, so that the results of thrombolysis are expressed in terms of coronary patency and improvement in segmental kinetics. The results of these different sets of studies have proved to be similar with time. Urokinase, notably when injected intravenously, has a beneficial effect in the acute phase of MI when compared to the conventional treatment. The coronary reperfusion obtained with urokinase is favourable to the myocardium, and the sooner it occurs the better. This benefit is demonstrated by clinical, electrical, enzymatic and angiographic data. Thus, despite its cost, urokinase remains useful in the treatment of MI, notably because it is well tolerated.(ABSTRACT TRUNCATED AT 250 WORDS)
Arch Mal Coeur Vaiss 1987 May
PMID:[Role of urokinase in the acute phase of myocardial infarction]. 311 77

The purpose of this study was to evaluate the effectiveness and desirability of a double fibrinolytic treatment in subacute venous thrombosis of the lower limbs. Thirty-four patients (mean age 55.2 +/- 15.4 years) hospitalized for thrombosis of deep lower limb veins were treated with two different fibrinolytic drugs administered successively: 23 patients received streptokinase first followed urokinase, and 11 patients received urokinase first followed by streptokinase. The overall results that improvement of the phlebographic score (Ph.s) was significantly greater in double fibrinolytic treatment (delta Ph.s. = 4.41 +/- 6.45, p less than 0.001) than after a single fibrinolytic treatment (delta Ph.s. = 3.14 +/- 4.76, p less than 0.001). Individual analysis of the results showed that 28% of the patients were improved by a second fibrinolytic treatment. It would appear that two fibrinolytic treatments are truly effective, albeit inconstantly and in most cases partially. We were unable in this study to determine the characteristics of patients likely to benefit from a double treatment.
Arch Mal Coeur Vaiss 1987 Jul
PMID:[Effectiveness of double fibrinolytic treatments in subacute deep vein thrombosis of the lower limbs]. 312 Jun 61

An unusual case of transient electro-mechanical dissociation concomitant with myocardial reperfusion is reported. The patient had myocardial infarction caused by occlusion of the middle anterior interventricular artery relieved by injection of urokinase and plasminogen in situ. The dissociation could be documented by simultaneous ECG recording on 3 leads and direct intravascular recording of femoral arterial pressure, the patency of that artery, and its maintenance, being demonstrated by angiography. This clinical case can be added to the list of events which occur during reperfusion of the myocardium after prolonged ischaemia. Its mechanisms, so far, are purely conjectural.
Arch Mal Coeur Vaiss 1987 Aug
PMID:[Electro-mechanical dissociation concomitant with myocardial reperfusion in the acute phase of myocardial infarction]. 312 94

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

After describing the mechanism of action, results and local and general complications of classical thrombolytic agents (streptokinase and urokinase) administered systemically, locally and peroperatively, then of modern thrombolytic agents (acyl enzyme, tPA and scuPA), the future perspectives of arterial fibrinolysis are discussed. These are based upon: analysis of the comparative efficacy of the different thrombolytic agents in the light of results seen, not only in peripheral arterial pathology but also in other indications, as in coronary pathology; discussion of the methods of administration of the thrombolytic agent in such a way as to obtain an optimal local concentration and at the same time reduced systemic fibrinolysis. better definition of the indications of thrombolysis in acute ischemia of the limbs in comparison with other therapeutic approaches, in particular surgery, taking into account the degree of ischemia, of etiological mechanism and the site of the arterial obstruction.
J Mal Vasc 1988
PMID:[Arterial thrombolysis. Review and future prospects]. 314 94

A 36 year old woman developed two thromboses on aortic valve prosthesis. The first thrombus at the 14th week of pregnancy was treated with urokinase (2,000 U/kg/h) plus heparin (700-1,000 U/h) over 24 hours and normal wing kinetics were obtained. The second thrombus developed at the 36 th week of pregnancy when the patient was receiving calciparin, and only transient improvement was obtained with similar doses of urokinase hourly over 72 hours. Progressive worsening resulted in higher doses (4,000 U/kg/h) being given without heparin and the thrombus then resolved. The use of urokinase for the first time in this indication allowed therefore, on two occasions and without hemorrhagic complications the cure of this recurrent thrombosis on aortic prosthesis, and the birth, by caesarean, of a healthy baby.
J Mal Vasc 1988
PMID:[Recurrent thrombosis of an aortic valve prosthesis in a pregnant woman. Treatment with urokinase]. 334 15

Fibrinogenolysis induced by thrombolytics exposes the risk of haemorrhagic complications. The efficacy is proved for pulmonary emboli of recent origin. The aim of this study is to research into the effect of local administration of low dose urokinase in six patients aged 40 (+/- 16 years) and presenting with old emboli (10 +/- 4 days). The initial clinic picture was serious with shock (2 cases), hypoxaemia (6 cases), pulmonary arterial hypertension (mean 40 +/- 8 mmHg) and a Miller index of 58 (+/- 8%). Mechanical ventilation was necessary four times. Urokinase was administered in situ using a Swan Ganz catheter, with 1,000 units per Kg per hour for six hours followed in sequence with 30 microkatals per hour of plasminogen for two hours. This eight hourly rotating sequence was followed for at least 72 hours. Six patients were cured with an end of treatment (5 +/- 2 days) improvement in their hypoxaemia of 22%, a fall of 47% of the pulmonary arterial pressure and a rise of 71% in the Miller index. The fibrinogenesis fell by 11% and the thrombolytics could not blamed for any side-effect. The sequence urokinase-plasminogen in low dose administered locally may represent an alternative treatment for severe and long standing pulmonary emboli in patients with a risk of haemorrhage.
Rev Mal Respir 1987
PMID:[Value of thrombolysis in situ without general fibrinogenolysis in pulmonary embolisms of more than 5 days duration]. 344 74

A case of double right and left intraventricular thrombosis diagnosed by 2D echocardiography is reported in a 20 year old man with nephrotic syndrome with eosinophilia and hypercoagulability, admitted as an emergency for a staphylococcal septicaemia in shock and anuria. Anticoagulation with heparin did not prevent two episodes of pulmonary embolism. Complete dissolution of the thrombi was obtained by peripheral administration of fibrinolytic therapy (urokinase and plasminogen). The authors discuss the differential diagnosis of echocardiographic appearances of biventricular masses and possible causes of these thrombi are suggested.
Arch Mal Coeur Vaiss 1985 Feb
PMID:[Biventricular thrombosis in nephrotic syndrome with hypercoagulability and hypereosinophilia]. 392 Sep 99

Low dose urokinase-lys plasminogen was used to treat 10 patients with acute ischemia of lower limbs. Preliminary results are reported and indications defined, the combination producing effective relief and being very well tolerated biologically and clinically. All patients presented clear signs of ischemia provoking a short term risk for the limb. Direct femoral puncture arteriography of the ischemic limb was an essential pretreatment investigation. A thin catheter left in contact with the thrombus allowed localized fibrinolysis to be performed. Follow up arteriography examinations assessed clinicopathologic results, while biologic surveillance of principal coagulation parameters showed a lack of significant alterations during treatment. Ischemic signs were totally relieved in 7 cases, with arterial repermeabilization allowing recuperation of one (3 cases) or both (2 cases) distal pulses. Persistence of a popliteal thrombus in one case required a fogarty after a direct approach and the limb was saved. Two patients had to be amputated because of delayed treatment. These encouraging results suggest that this procedure of local thrombolysis be reserved for popliteal or infra-popliteal occlusions accompanied by sensory-motor signs and of recent (less than 72 hours) onset. Follow up for 8 months is insufficient but has shown the absence of deterioration, but this is obviously a function of the natural course of the underlying atheromatous disease.
J Mal Vasc 1985
PMID:[Indications and results of combined urokinase-lys plasminogen in acute ischemic pathology of the legs]. 409 20


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