Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.68 (tissue plasminogen activator)
 11,311 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated whether tissue-type plasminogen activator antigen (t-PA-Ag) was associated with intake of meat, fish, or dairy products. The study population comprised 295 women and 299 men aged 30-64 years, which was a random sample from the D.E.S.I.R. (Data from an Epidemiological Study on the Insulin Resistance syndrome) study comprising 5214 men and women in total. T-PA-Ag was measured in fasting blood samples and the habitual intake of foods was assessed by several questions on a food frequency questionnaire. Cross-sectional data were analyzed. The mean t-PA-Ag concentration was 3.28 ng/mL (SD, 1.26) in men and 2.52 ng/mL (SD, 1.22) in women. The concentration of t-PA-Ag was inversely associated with the consumption of milk and milk products in women (p for trend: 0.15) and in men (p for trend: 0.04). The difference between subjects with a low and a high milk consumption was 13% in women and 19% in men. Similar results were observed for consumption of cheese. The concentration of t-PA-Ag was 21 and 8% lower for women and men with a high cheese consumption, respectively, compared to those with a low consumption. Further analyses showed that the association of t-PA-Ag with milk and milk product consumption was independent of cheese consumption and vice versa. No association between meat or fish intake and t-PA-Ag was observed. The results of this study indicate that, if confirmed by others, a high intake of dairy products may influence fibrinolysis by an effect on t-PA-Ag.
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PMID:Tissue-type plasminogen activator antigen and consumption of dairy products. The DESIR study. Data from an Epidemiological Study on Insulin Resistance Syndrome. 1039 Jan 33

The present study compared the antithrombotic properties of fractionated aurin tricarboxylic acid (ATA), an inhibitor of platelet glycoprotein (GP) Ib, and GR144053, a GPIIb/IIIa antagonist, in a hamster model of stenosis. Endothelial cell injury in the hamster carotid artery was achieved by a 2F modified catheter. Arterial blood flow in the control groups was interrupted 5.4+/-0.9 minutes after the injury. When ATA (0.01, 0.03, 0.1, 0.3, and 1.0 mg/kg per hour) or GR144053 (0.1, 0.3, and 1.0 mg/kg per hour) were continuously infused intravenously, the time elapse before the vessel completely occluded was prolonged in a dose-dependent manner. However, all arteries in the ATA-treated groups ultimately occluded during the observation period even if the aggregation of platelets ex vivo and induced by botrocetin was completely inhibited. When either ATA (0.1 mg/kg per hour) or GR144053 (0.3 mg/kg per hour) were infused via an implanted osmotic pump together with tissue-type plasminogen activator (tPA), late patency of the reperfused artery was improved compared to that of arteries treated with TPA alone. However, the cyclic reflow pattern after reperfusion on days 0 and 1 was not reduced by the ATA treatment. The bleeding time was significantly prolonged when either ATA or GT144053 was coadministered with tPA. The treatment with ATA showed an especially marked prolongation of the bleeding time. In conclusion, both inhibition of platelet activation by ATA or GR144053 prevent arterial thrombosis and enhance the thrombolytic effect of tPA, but GR144053 was more protective in its antithrombotic effect and more effective during thrombolytic therapy than ATA.
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PMID:Comparison of the antithrombotic effects and bleeding risk of fractionated aurin tricarboxylic acid and the GPIIb/IIIa antagonist GR144053 in a hamster model of stenosis. 1040 86

Reperfusion of intracranial arteries can be detected by transcranial Doppler (TCD). The authors report microembolic signals (MES) on TCD as a sign of clot dissolution and recanalization. Microembolic signals were detected during routine diagnostic TCD examination performed in the emergency room in patients eligible for thrombolytic therapy. Microembolic signals were found at the site of M1 middle cerebral artery (MCA) high-grade stenosis or near-occlusion. Transcranial Doppler was performed before, during, and after thrombolytic therapy. Of 16 consecutive patients, 3 (19%) had MES on TCD. All three patients had a severe MCA syndrome at 2 hours after stroke onset scored using the National Institutes of Health Stroke Scale (NIHSS). In patient #1 (NIHSS 12), clusters of MES were detected distal to a high-grade M1 MCA stenosis preceding spontaneous clinical recovery by 2 minutes. Because of subsequent fluctuating clinical deficit, intraarterial thrombolysis was given with complete recovery. In patient #2 (NIHSS 20), TCD detected an M1 MCA near-occlusion. At 1.5 hours after intravenous tissue plasminogen activator, TCD showed minimal MCA flow signals followed by MES, increased velocities, and normal flow signals in just 2 minutes. She gradually recovered up to NIHSS 8 in 5 days. In patient #3 with NIHSS 22 and an M1 MCA near-occlusion, TCD detected MES 15 minutes after TPA bolus followed by MCA flow velocity improvement from 15 cm/sec to 30 cm/sec. The patient recovered completely by the end of tissue plasminogen activator infusion. The authors conclude that embolic signals detected by TCD at the site of arterial obstruction can indicate clot dissolution. Intracranial recanalization on TCD can be associated with MES and changes in flow waveform, pulsatility, and velocity if insonation is performed at the site of arterial obstruction.
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PMID:Intracranial clot dissolution is associated with embolic signals on transcranial Doppler. 1066 79

Stroke is a heterogeneous disease, but about 85% of strokes are as a result of cerebral ischaemia due to arterial occlusion. It seems logical to assume that, as in myocardial infarction, treatment designed to dissolve clots should be helpful. We now have a substantial amount of data on the use of aspirin, heparin and thrombolytic drugs in the treatment of acute ischaemic stroke. Aspirin 300 mg daily has a modest effect in reducing mortality and handicap when used within 48 hours of stroke onset. The beneficial effects of low dose, medium dose subcutaneous unfractionated heparin, and various low molecular weight heparins in reducing early recurrent ischaemic stroke seem to be outweighed by haemorrhagic side effects. Streptokinase used within six hours of stroke onset results in excess mortality with some reduction in handicap in survivors, while in carefully selected patients recombinant tissue plasminogen activator (r-TPA) may be less hazardous. At the moment it is unclear which stroke patients will benefit from the use of r-TPA, and the use of criteria, as outlined by the NINDS group, means that only a very small proportion of stroke victims are suitable for thrombolytic therapy. Further research is necessary, while the concept of a 'Brain Attack' with appropriate urgency being used in the assessment of possible stroke needs development.
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PMID:Reperfusion therapy for stroke. 1086 20

In 10 patients with chronic renal insufficiency we are tissue plasminogen activator antigen (t-PA Ag), tissue plasminogen activator inhibitor (PAI-1) and euglobulin lysis time (ELT) designed. This parameters are just before hemodialysis, in 60 minutes and 240 minutes after beginning of dialysis studied. In 60 minutes after the beginning of hemodialysis significant increased tissue plasminogen activator inhibitor antigen, decreased tissue plasminogen activator inhibitor activity and prolonged euglobulin lysis time. The observed increase in plasma t-PA antigen levels during hemodialysis is due to effects of extracorporal circulation on the fibrinolytic system. T-PA release and consequent consumption of tissue plasminogen activator inhibitor due to enhanced fibrinolytic activity during hemodialysis.
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PMID:[Tissue plasminogen activator antigen (t-PA Ag) and tissue plasminogen activator inhibitor (PAI-1) in the course of hemodialysis in patients with chronic renal failure]. 1090 30

A girl with Down's syndrome, moyamoya disease and sagittal sinus thrombosis is described. She was diagnosed after acute neurological deterioration by MRI and angiography. Recombinant tissue plasminogen activator (r-TPA) was injected locally to recanalise the thrombus. The patient's condition significantly improved and she was discharged. After 2 years of follow-up the child remains asymptomatic. Moyamoya syndrome and cerebral venous thrombosis should not be overlooked as a cause of acute neurological deterioration in a child with Down's syndrome. MRA appears to be a safe and accurate alternative to traditional angiography for the diagnosis of moyamoya disease. Local fibrinolysis with r-TPA is the treatment of choice for cerebral venous thrombosis due to its safety and efficacy.
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PMID:Moyamoya disease and sagittal sinus thrombosis in a child with Down's syndrome. 1121 82

The ability of the rodent brain to support plasticity-related phenomena declines with increasing age. A decreased coordination of genes implicated in brain plasticity may be one factor contributing to this decline. Synaptic rearrangement that occurs after seizure activity is regarded as a model of brain plasticity. In a rat model of seizure-related brain plasticity, we found that the induction of immediate-early genes, as exemplified by c-fos and tissue plasminogen activator ( tPA), is not impaired in the aged rat brain. However, the aged rat brain responded more slowly to chemically induced seizure, and the levels of c-fos and tPA mRNAs induction are decreased in the cortex and in the hippocampus of 30 month old rats, as compared to the levels expressed by 3 month old rats. In addition, at the peak induction, the TPA transcripts were restricted to certain cortical layers of the older rats. Surprisingly, in applying the same experimental paradigm to late genes, we found that there was a shift toward earlier times in the maximum expression of growth-related molecules, the microtubule-associated protein 1B (MAP1B) mRNA, which was very evident in 18 month old rats. Aberrant immunolabeling of MAP1B occurred in cortical layer VI of the aged rats where, unlike in young rats, there was heavy staining of neuronal somata. These results suggest that (1) one consequence of aging, besides decreases in the levels of mRNA, is a progressive loss of coordination in gene activity following the administration of a stimulus; (2) since c-fos, TPA and MAP1B have been implicated in neuronal plasticity, these findings could explain, in part, the limited plasticity of the aging brain.
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PMID:Dynamics of gene expression for immediate early- and late genes after seizure activity in aged rats. 1139 67

To clarify the possible role of persistent thrombocytosis after splenectomy as being a predisposing factor causing thromboembolism. Blood coagulation profiles were studied in 35 patients (20 M and 15 F, mean age 42 +/- 17.5) suffering from thrombocytosis (> 500,000/dl) who underwent splenectomy for non-malignant and non-traumatic diseases. Seventy healthy subjects acted as a control group. Tests were performed 6 months after the operation and for both groups (patients and controls) blood samples were collected for: platelets, fibrinogen, PT, APTT, AT III, plasminogen, F1 + 2, t-PA and DNA analysis for F V, F II and MTHFR. After one year all subjects were controlled for thrombocytosis, genomic abnormalities and venous thrombosis. All the analyses were performed according to the Statistical Package for Social Science. The significance of the differences in means was evaluated by non-parametric tests, differences with a P value < 0.05 being considered significant. Increased plasma levels of fibrinogen, D-dimer, F1 + 2 and PAI-1 were found in the patients compared with the control group. TPA was significantly lower in the patients than in the controls. At the one year follow-up, two patients with genetic polymorphism had suffered deep venous thrombosis. Our findings indicate that splenectomy contributes to abnormal platelet aggregation and endothelial cell activation with hypercoagulability.
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PMID:[Blood coagulation changes in patients with post-splenectomy persistent thrombocytosis]. 1158 73

Thrombolytic therapy of a systemic pulmonary fistula is a rare method of treatment in newborns with thrombosed systemic-pulmonary shunt. We report the case of a newborn girl with a complex congenital heart defect. On the ninth day of life a modified right Blalock-Taussig shunt was performed. The ductus arteriosus was not ligated. Six days later the baby developed severe hypoxemia. The results of echocardiography and cardiac catheterization showed a total thrombosis of the fistula and complete absence of flow throughout the shunt. After insertion of an arterial catheter into the proximal end of the shunt we started fibrinolytic treatment with recombinant tissue plasminogen activator (r-TPA) in continuous infusion. After 14 hours of treatment we confirmed by angiography complete clot dissolution. The baby left the hospital in good condition when she was 23 days old. In the follow-up (4th month of life) the shunt is still permeable. Thrombolytic therapy with r-TPA locally applied in case of acute thrombosis of a systemic-pulmonary shunt appears to be a good therapeutic option avoiding the risks of a new surgical procedure.
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PMID:[Fibrinolytic treatment with tissue plasminogen activator in a thrombosed modified Blalock-Taussig shunt]. 1176 93

Ischaemic penumbra is defined as the area of brain tissue that maintains some blood flow following ischaemic accident. This zone may be rescued by both neuroprotection and arterial revascularization. Early thrombolysis has been used with encouraging results since 1995 in several trials testing both streptokinase and recombinant tissue plasminogen activator (r-TPA): the r-TPA results are definitely more positive than those of streptokinase, despite an increased incidence of symptomatic haemorrhagic transformation, r-TPA significantly reducing death or dependency at the end of follow-up. Despite the fact that some experimental periods of application of these therapeutic strategies demonstrated real cost-effective benefits, only 1% of patients reaching hospital in time for thrombolysis are currently treated. This is because the profile of patients at risk of haemorrhagic transformation, which is definitely the most feared side-effect of thrombolysis in stroke, is yet to be clearly defined. Extended computerized tomography (CT) signs of the index stroke have been repeatedly indicated as reliable predictors of haemorrhagic transformation even if currently there are significant discrepancies in the criteria adopted by different researchers to define early CT signs. Based on experimental ischaemia, strategies for protecting the basal lamina during thrombolysis are suggested: neuroprotection is the second approach to stroke therapy; pharmacological reperfusion and brain protection are probably mutually dependent.
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PMID:Treatment of cerebrovascular diseases: state of the art and perspectives. 1181 86


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