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)

The aim of using enzymes in vitreoretinal surgery is to facility PVD and create pharmacological vitrectomy. It can be achieved by liquefying the gel structure of the vitreous (synchisis) and weakening of adherence of the posterior vitreous cortex to retina (syneresis). The article reviews currently used enzymes in vitreoretinal surgery (plasmin, hyaluronidase, dispase, chondroitinase, collagenase, urokinase, TPA--tissue plasminogen activator) and presents potential profits and side-effects related to their use. Although the day when vitreous surgery is replaced by pharmacological vitreolisis remains still as a future, these enzymes hold great promise. Additionally it has been proved that enzymes can be used successfully as an intraoperative adjuvant in vitrectomy.
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PMID:[Use of enzyme in vitreoretinal surgery]. 1204 13

In this study, we investigated the dose-effect relationship and safety of tissue plasminogen activator (tPA) for the treatment of intraventricular hemorrhage/hematoma (IVH) in rats. Adult male Sprague-Dawley rats were injected with autologous blood into the left lateral ventricle to establish IVH. Two hours later, Ringer's saline or 0.25-2 microg of tPA were administered directly to the IVH over 3 h. The regional cerebral blood flow (rCBF) on the surface of the left parietal cortex was measured with laser Doppler flowmetry. Twenty-four hours after the build-up of IVH, the brains were removed for morphometrical and histological studies. A dose of 0.5-2 microg tPA significantly diminished the IVH in a dose-dependent manner (p < 0.001). However, only the dose of 0.5 microg tPA significantly ameliorated the reduction of rCBF 24 h after IVH (p < 0.01). TPA did not improve the ventricular dilatation on the side with IVH. Instead, 1-2 microg of tPA caused additional injuries, including intraventricular leukocytosis and edema of periventricular tissues and choroid plexus on both hemispheres. These results indicate that higher doses of tPA may have detrimental effects on the brain. The dosage rate of 0.5 microg seems beneficial to treat 5 microl of IVH (equals to a dose of 0.1 mg/ml blood) in our model in terms of the satisfactory fibrinolysis and less damage to the brain.
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PMID:Tissue plasminogen activator for the treatment of intraventricular hematoma: the dose-effect relationship. 1222 Jun 85

We examined the diurnal pattern in Plasminogen Activator Inhibitor-type 1 (PAI-1) activity and Plasminogen activator (t-PA) in relation to the 4G/5G-polymorphism in the promoter of the PAI-1 gene. The analyses were performed in the Arnhem Elderly Study, a population-based study of 598 elderly. A single blood sample was drawn and the time of blood sampling was recorded (between 8 a.m. and 5.30 p.m.). Plasma PAI-1 activity was strongly associated with time of blood sampling, showing the highest values in the early morning. The diurnal pattern was clearly present in the 4G/4G (n = 184) and 4G/5G (n = 275) genotypes, but not in the 5G/5G-genotype (n = 139). T-PA antigen showed a weak diurnal variation, which did not differ across the variants of the 4G/5G-polymorphism. Our findings raise the hypothesis that 5G-homozygotic persons may be relatively protected from diurnal variation in the occurrence of coronary events.
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PMID:Diurnal variation in PAI-1 activity predominantly confined to the 4G-allele of the PAI-1 gene. 1242 96

YM872, an AMPA receptor antagonist, was administered together with t-PA to investigate the effects of coadministration on neuroprotection in a rat embolic stroke model, when administered 2 h after embolism. T-PA or YM872 alone decreased infarct volume and improved the neurological deficit score. Coadministration of YM872 and t-PA resulted in a further decrease in infarct volume and improvement of the neurological score as compared with single administration of t-PA. These data demonstrate that coadministration of YM872 and t-PA produces more potent neuroprotective effects than when t-PA is administered alone.
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PMID:Neuroprotective effects of YM872 coadministered with t-PA in a rat embolic stroke model. 1248 Jan 71

Vascular events caused by atherosclerosis are the major cause of death in patients undergoing hemodialysis (HD). The relationship between the tests of atherosclerosis and hemostasis in 84 patients with HD was examined. Abnormal test results indicting the occurrence of atherosclerosis were found in 66% by the Fontaine score, in 33% by ankle blood pressures, and in 79% by aortic calcification index (ACI). When HD was prolonged, the mean Fontaine score and ACI were further increased. Particularly, the ACI tended to correlate with HD duration. The ankle-brachial index (ABI) was decreased in patients with HD duration of more than 10 years. Before HD, the plasma levels of fibrinogen, plasmin-plasmin inhibitor complex (PIC), thrombomodulin (TM), and D-dimer were increased, while the plasma levels of protein C (PC), antithrombin (AT), thrombin-antithrombin complex (TAT), and tissue plasminogen activator (tPA)-plasminogen activator inhibitor-I (PAI-I) complex (tPA-PAI-1 complex) were decreased. With prolonged HD, the plasma levels of AT and PC were decreased, while those of D-dimer were increased. The plasma levels of TAT and TPA-PAI-1 complex were significantly increased and those of PIC, soluble fibrin (SF) and D-dimer tended to be high in patients with less than 0.7 of ABI. The plasma levels of D-dimer, TPA-PAI-1 complex, TAT, PIC, and SF tended to be high in patients with more than 0.5 in ABI. These findings suggest that patients undergoing HD have progressive atherosclerosis and that this is associated with some hemostatic abnormalities.
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PMID:Atherosclerotic and hemostatic abnormalities in patients undergoing hemodialysis. 1264 24

The outer surface protein C (OspC) of Borrelia burgdorferi, the spirochete that causes Lyme disease, is a promising candidate for a vaccine against borreliosis. BALB/c and C3H/HeJ mice were immunized either with recombinant OspC protein or with plasmid DNA encoding OspC fused to the human tissue plasminogen activator leader sequence (pCMV-TPA/ZS7). The influence of the route of administering the DNA and the use of oligodeoxynucleotides containing CpG-motifs on the development of the immune response was investigated. In both mouse strains, protein as well as gene-gun immunization induced Th2 type responses, whereas needle injection of plasmid DNA resulted in Th1 type antibody production. Co-injection of CpG-motifs did not significantly modify the response type in any immunization group, as indicated by only marginal changes of antibody subclass distribution. The protection rate after challenge with 10(4) B. burgdorferi organisms per mouse was between 80% and 100% for all groups. These results demonstrate, for the first time, that a DNA vaccine encoding OspC of B. burgdorferi is suitable for inducing protection against Lyme borreliosis.
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PMID:A DNA vaccine encoding the outer surface protein C from Borrelia burgdorferi is able to induce protective immune responses. 1294 85

Neuroserpin is a member of the serine proteinase inhibitor (serpin) gene family that reacts preferentially with tissue-type plasminogen activator (tPA) and is primarily localized to neurons in regions of the brain where tPA is also found. Outside of the central nervous system (CNS) tPA is predominantly found in the blood where its primary function is as a thrombolytic enzyme. However, tPA is also expressed within the CNS where it has a very different function, promoting events associated not only with synaptic plasticity but also with cell death in a number of settings, such as cerebral ischemia and seizures. Neuroserpin is released from neurons in response to neuronal depolarization and plays an important role in the development of synaptic plasticity. Following the onset of cerebral ischemia there is an increase in both tPA activity and neuroserpin expression in the area surrounding the necrotic core (ischemic penumbra), and treatment with neuroserpin following ischemic stroke or overexpression of the neuroserpin gene results in a significant decrease in the volume of the ischemic area as well as in the number of apoptotic cells. TPA activity and neuroserpin expression are also increased in specific areas of the brain by seizures, and treatment with neuroserpin slows the progression of seizure activity throughout the CNS and results in significant neuronal survival in the hippocampus. Mutations in human neuroserpin result in a form of autosomal dominant inherited dementia which is characterized by the presence of intraneuronal inclusion bodies and is known as Familial Encephalopathy with Neuroserpin Inclusion Bodies.
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PMID:Neuroserpin: a selective inhibitor of tissue-type plasminogen activator in the central nervous system. 1498 20

Myointimal hyperplasia is the condition usually responsible for recurrent stenosis (restenosis) after endarterectomy, bypass grafting and angioplasty. Its cause is still not known. The present study examined whether inhibition of thrombin by tissue plasminogen activator (r-TPA) or polyethylene glycol recombinant hirudin (PEG-hirudin) could reduce restenosis in an animal model. Restenosis was induced in 20 cholesterol-fed rabbits. The right carotid artery underwent a double-balloon injury while left carotid artery acted as a control. Recombinant tissue plasminogen activator (1 mg kg(-1) s.c.) and PEG-hirudin (0.7 mg kg(-1) s.c.) were given subcutaneously with normal saline acting as a control. Blood levels of PEG-hirudin were measured by both ELISA and an Ecarin (activity) assay. Vessel dimensions were measured in histological sections, obtained from perfusion-fixed tissue, using computerised planimetry. The model reproduced many of the histological changes found in human restenosis, such as intramural thrombus, rupture of the elastic lamina, macrophage infiltration and smooth muscle migration. Reinjury caused an almost three-fold reduction in the area of the lumen (median 0.25 mm(2)) compared with uninjured vessels (median 0.72 mm(2)). The mean plasma levels of PEG-hirudin and r-tPA achieved were 291 ng/ml (S.E.M. 28 ng/ml) and 34 IU/ml (S.E.M. 12 IU/ml), respectively. PEG-hirudin significantly inhibited the effect of balloon injury on luminal area compared with saline-treated controls (0.21 versus 0.44 mm(2), respectively, P<0.05). Recombinant tPA also had a similar inhibitory affect, but this did not reach statistical significance (0.16 versus 0.44 mm(2), respectively, P>0.05). The magnitude of luminal narrowing was significantly reduced by subcutaneous injection of PEG-hirudin. Further studies are required to determine whether this effect can be enhanced by other antithrombins or improved methods of delivery.
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PMID:The effect of anticoagulation with subcutaneously delivered polyethylene glycol conjugated hirudin and recombinant tissue plasminogen activator on recurrent stenosis in the rabbit double-balloon injury model. 1511 71

Presented are the clinical data of 18 consecutive patients who were treated by IV recombinant tissue plasminogen activator (r-TPA) for suspected vertebrobasilar (VB) acute ischemia within 7 hours. The mean delay for treatment was 5 +/- 3.6 hours. Mean baseline NIH Stroke Scale score was 17 +/- 4. At 3 months, 10 patients were independent (modified Rankin Scale [mRS] score = 0 to 2), whereas 8 patients showed a poor outcome (mRs = 3 to 6). IV r-TPA in VB ischemia in a 7-hour window may be safe and efficient.
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PMID:Intravenous r-TPA in vertebrobasilar acute infarcts. 1515 94

Since July 2002 we have been conducting a study of efficacy of prehospital thrombolytic therapy combined with subsequent endovascular procedures in the treatment of patients with acute myocardial infarction. Fifty nine patients received prehospital fibrinolysis with tissue-type plasminogen activator (TPA, n=28) or streptokinase (n=31) within 6 hours after onset of symptoms. TPA infusion compared with that of streptokinase was associated with smaller ischemic myocardial damage and lower frequency of side effects (3.6 and 38.7%, respectively). Angioplasty or stenting of infarct related arteries were carried out in 47 of these patients. The group of patients subjected to endovascular interventions was characterized by a low rate of in-hospital cardiac events and zero mortality.
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PMID:[Combination of prehospital systemic thrombolytic therapy with endovascular procedures in the treatment of patients with acute myocardial infarction]. 1582


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