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)

Urokinase is a plasminogen activator of human origin which breaks up the fibrin base of blood clots. When given as an intravitreal injection it produces hypopyon and glaucoma, both of which transient. In a series of 27 patients (34 eyes) with unresolved vitreous haemorrhage, this simple and relatively atraumatic treatment has produced marked objective improvement in 10, and greatly improved the life styles of a further 9. This series brings the total of reported cases to 93. When compared with recent American reports of surgical vitrectomy for vitreous haemorrhage, intravitreal urokinase appears to have a higher success rate, with a lower complication rate both in the short and long term. This study suggests that, despite the high cost of the purified enzyme, urokinase should be come the first line of attack in vitreous haemorrhage, vitrectomy being reserved for those patients who fail to respond.
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PMID:Urokinase in the management of vitreous hemorrhage. 91 29

Recombinant tissue-type plasminogen activator (rt-PA), streptokinase (SK), and anisoylated plasminogen-streptokinase activator complex (APSAC) have salutary effects on mortality when administered to patients with evolving acute myocardial infarction (MI). Studies suggest that intravenous rt-PA is more effective in reperfusing occluded infarct-related arteries than SK, and the results of ongoing studies directly comparing the influence of SK and rt-PA on mortality are awaited. The clinical role of agents such as APSAC, urokinase, and pro-urokinase, used alone or in combination, remains to be determined. It is evident that a variety of thrombolytic agents will be effective, and variables such as ease of administration, pharmacokinetics, fibrin specificity, effects on blood viscosity, and incidence of adverse effects need to be assessed to determine which agents are the most suitable for clinical use. There is an increased risk of bleeding at vascular puncture sites with all thrombolytic agents. Current indications for thrombolytic therapy include ischemic chest pain of at least 30 min duration that is unrelieved by nitroglycerin and is associated with ST-segment elevations of at least 0.1 mV in two contiguous electrocardiographic leads. Such therapy is usually reserved for patients less than 75 years old who are not at increased risk for bleeding and whose chest pain began less than 4-6 prior to treatment. Trials are under way to determine whether patients with shorter pain duration, transient ST-segment changes (ie, unstable angina patients), chest pain associated with ST-segment depressions or T-wave inversions (ie, non-Q-wave infarction patients), or patients whose pain began more than 4 to 6 h earlier will benefit from early thrombolytic therapy. Other factors such as patient age, the likelihood of the diagnosis of MI, and the estimated risk of bleeding should also be considered. The findings of available major randomized trials indicate that early invasive procedures are generally unnecessary and that meticulous care must be exercised in the selection and management of patients subjected to thrombolytic therapy.
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PMID:Thrombolytic therapy in acute myocardial infarction. 210 51

A group of 456 consecutive patients seen less than or equal to 6 h after the onset of acute myocardial infarction associated with ST segment elevation received thrombolytic therapy and were followed up for 12 months. Intravenous streptokinase was given to 315 patients and recombinant tissue-type plasminogen activator (rt-PA) to 141 patients. Reinfarction rate and risk factors for reinfarction were assessed. Management after thrombolysis was conservative; revascularization procedures were reserved for patients with symptoms refractory to medical therapy or for those with left main coronary artery stenosis. Coronary artery surgery or angioplasty was performed in only 3.7% of patients during the first 30 days after thrombolysis and in only 8.6% by 1 year. Most patients (79%) underwent coronary arteriography. Twenty-six patients (5.7%) exhibited signs of threatened reinfarction at 1 month after thrombolytic therapy as did 43 patients (9.4%) by 1 year. Reinfarction was prevented in four of these patients by early readministration of thrombolytic therapy. Multivariate analysis of possible risk factors for reinfarction identified at the time of initial infarction showed current cigarette smoking to be the only predictive factor (reinfarction occurred in 12.5% of smokers versus 6.3% of nonsmokers, p = 0.04). A second analysis of risk factors identified 3 weeks after initial infarction, including the severity of residual stenosis at coronary arteriography and exercise test variables, again showed continued cigarette smoking to be the only factor predictive of reinfarction. Twenty percent of patients who continued to smoke developed reinfarction compared with 5.1% of those who stopped (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reinfarction after thrombolytic therapy for acute myocardial infarction followed by conservative management: incidence and effect of smoking. 211 38

The accepted role for thrombolytic therapy has until recently been limited because of its complexity and side-effects. It has generally been reserved for use systemically in a limited number of patients with acute, major pulmonary embolism or iliofemoral venous thrombosis, and locally in some patients with acute, peripheral arterial occlusion. Its indications have now been greatly expanded by the confirmation from large, multicentre trials completed within the last year that it is also effective in acute myocardial infarction, with a reduction in acute mortality of 20-25%. Moreover, administration has become greatly simplified as dosage regimens have been standardised and the need for laboratory monitoring eliminated. The standard thrombolytic agent used for nearly 3 decades has been streptokinase but within the last year recombinant, human, tissue-type plasminogen activator (the first 'third generation' thrombolytic agent) has become clinically available. This protein is the body's own chief plasminogen activator and has been produced by recombinant DNA technology. Compared with streptokinase, it appears to be both somewhat more effective and also safer (less bleeding and probably no allergic reactions). Other new thrombolytic agents are also being developed but the cost-effectiveness of the newer agents in relation to streptokinase will be for many the main practical issue.
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PMID:Thrombolytic therapy. 249 35

In this three year prospective study of 177 patients with acute peripheral arterial ischemia those subjects with acute iliofemoral emboli or ischemia with a neurosensory deficit had urgent operations. The remainder included patients less likely to have limb salvage after surgery and who therefore were treated with thrombolytic therapy. This was done in three open studies of intravenous, acylated, plasminogen-streptokinase activator complex, low dose intraarterial streptokinase and intraarterial tissue-plasminogen activator (t-PA). The overall outcome after 30 days of thrombolytic therapy was limb salvage (55%), amputation (15%), and death (30%). The severity of the presenting ischemia was the most important prognostic indicator. In patients with a neurosensory deficit, limb salvage after either embolectomy or surgical reconstruction (59%) was more likely than after thrombolysis (31%). In patients without a neurosensory deficit, limb salvage after thrombolysis (68%) was better, though not significantly, than after surgery (53%). Local intraarterial thrombolysis with either streptokinase or t-PA produced an encouraging 66% limb salvage in 59 cases. In management of acute peripheral arterial occlusions an approach based on the severity of ischemia is optimal, with urgent surgery for patients with a neurosensory deficit and intraarterial thrombolytic therapy reserved as an alternative in selected cases with stable ischemia.
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PMID:Acute peripheral arterial ischemia: a prospective evaluation of differential management with surgery or thrombolysis. 251 79

Adjunctive therapy for acute myocardial infarction should include aspirin, beta-adrenergic blocking agents, and, in most patients, consideration of the use of angiotensin-converting enzyme inhibitors, especially if left ventricular function is reduced. Heparin has an important adjunctive role in enhancing early vessel patency in patients who receive tissue-type plasminogen activator and in decreasing the frequency of reocclusion of an infarct-related artery during any thrombolytic therapy. Heparin must also be administered to all patients who undergo primary angioplasty. Intravenously administered nitroglycerin and orally administered nitrates are probably most effective in patients with symptomatic ischemia. Calcium channel blockers and prophylactic antiarrhythmic agents are not indicated for most patients with acute myocardial infarction. Currently, insufficient evidence is available to recommend the widespread use of intravenously administered magnesium sulfate in the setting of acute myocardial infarction. In patients with ischemic pain, judicious intravenous administration of morphine can provide relief. Use of warfarin sodium should be reserved for patients at risk for left ventricular mural thrombus. Although the use of lipid-lowering agents after myocardial infarction has been controversial, recent studies have demonstrated the importance of such therapy for secondary prevention of death and morbidity.
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PMID:Adjunctive therapy in the management of patients with acute myocardial infarction. 773 Dec 56

Future surgical strategies to restore neurological function in peripheral nerve loss may involve replacement of nerve tissue with cultured Schwann cells using biodegradable guiding implants. Random copolymers of trimethylene carbonate and epsilon caprolactone (P(epsilonCL-TMC), 50: 50) have been synthesized by ring opening polymerization using rare earth alkoxides as initiator. Their potential use as nerve guide repairs has been assessed through indirect and direct in vitro biocompatibility tests and in vivo soft tissue response to EDI subclass macrophages. In vitro, we exposed monolayers of human skin fibroblasts and an established continuous cell line (Hela) to liquid extracts (either pure or diluted in the culture medium) of epsilonCL-TMC copolymer including positive (phenol) and negative controls. Then, colorimetric assays (Neutral red and MTT) were performed. The extracts of epsilonCL-TMC induced no significant cytotoxic effect. We also exposed in vitro Schwann cells to pieces of P(epsilonCL-TMC) and P(LA-GA) copolymers. We evaluated cell attachment at 1 and 3 h by measuring the activity of the lysosomal enzyme (N-acetyl-beta-hexosaminidase) and cell proliferation at 1, 3, 6 and 9 days by measuring the cell metabolic activity (MTT assay). Values for attachment slightly decreased between 1 and 3 h but were significantly higher than on agars (negative control). Cells plated on epsilonCL-TMC showed a rate of proliferation comparable with that of normalized controls and higher than on PGA-PLA at day 9. Finally, we evaluated in vivo the soft tissue response after implantation of cylindrical tubes of P(epsilonCL-TMC) and P(LA-GA) copolymers with an immunohistochemistry staining procedure for the newly recruited ED1 macrophages. An image analysis system automatically measured the optical density of labelled positive ED1 cells at 9, 21 and 60 days after implantation. epsilonCL-TMC copolymer showed a mild soft tissue reaction with no adverse chronic inflammatory reaction. These data allowed us to consider this conduit as a potential effective substitute in nerve repair. El sevier Science Ltd. All rights reserved.
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PMID:Study of a (trimethylenecarbonate-co-epsilon-caprolactone) polymer--part 2: in vitro cytocompatibility analysis and in vivo ED1 cell response of a new nerve guide. 1157 69

Atherosclerosis preferentially occurs in areas of turbulent flow and low fluid shear stress, while laminar flow and high shear stress are atheroprotective. Well characterized atheroprotective mechanisms include inhibition of thrombosis (increased tissue-type plasminogen activator and decreased plasminogen activator inhibitor-1), inhibition of endothelial cell apoptosis, limitation of permeability (uptake of low-density lipoprotein), prevention of white blood cell binding and transmigration (no expression of adhesion molecules such as intercellular adhesion molecule-1 [ICAM-1] and vascular cell adhesion molecule-1 [VCAM-1] and no release of monocyte chemotactic protein-1) and increased bioavailability of nitric oxide (because of increased expression of endothelial nitric oxide synthase and manganese superoxide dismutase). Our lab has investigated flow-mediated inhibition of inflammatory cytokine action. In particular, we have shown that flow prevents tumor necrosis factor-alpha (TNF-alpha) mediated signal transduction. TNF regulates inflammatory gene expression (e.g., ICAM-1 and VCAM-1) in endothelial cells, in part, by stimulating mitogen activated protein (MAP) kinases that phosphorylate transcription factors. We hypothesized that fluid shear stress inhibits TNF inflammatory effects on endothelial cells by inhibiting TNF mediated activation of the c-Jun N-terminal kinase. To test this hypothesis, we determined the effects of steady laminar flow on TNF-stimulated activity of c-Jun N-terminal kinase. The results show that flow inhibits c-Jun N-terminal kinase activation through multiple mechanisms, including stimulation of counter-regulatory MAP kinases (extracellular signal regulated kinases [ERK]1/2 and ERK5) and inhibition of apoptosis signal-regulated kinase. In summary, the atheroprotective effects of steady laminar flow on the endothelium involve multiple synergistic mechanisms. These multiple mechanisms offer attractive targets for new drug therapies aimed at limiting atherosclerosis development and progression. (c) 2002 Prous Science. All rights reserved.
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PMID:Atheroprotective Mechanisms Activated by Fluid Shear Stress in Endothelial Cells. 1267 55

Tenecteplase, a new fibrinolytic with longer plasma half-life and greater specificity for fibrin than alteplase, achieves rapid thrombolysis in patients with acute myocardial infarction. Similar TIMI grade 3 flow rates at 90 minutes have been observed with tenecteplase and alteplase. The efficacy and safety of tenecteplase have been confirmed in a large trial, ASSENT-2, demonstrating similar mortality rates at 30 days and a lower rate of noncerebral bleeding complications when compared with alteplase. The convenience of a single bolus treatment may facilitate the initiation of early and efficient reperfusion. (c) 2001 Prous Science. All rights reserved.
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PMID:Tenecteplase (TNK tissue plasminogen activator): A new fibrinolytic for the acute treatment of myocardial infarction. 1273 71

Recombinant thrombolytic peptides are mainly represented by recombinant forms of tissue plasminogen activator (t-PA), a proteolytic enzyme that catalyzes the conversion of plasminogen into active plasmin, which then functions to dissolve clots. The three clinically relevant recombinant thrombolytic peptides are alteplase (t-PA), reteplase (r-PA), and tenecteplase (TNK). r-PA and TNK have been structurally modified from native t-PA to increase their half-life and fibrin specificity. Thrombolytics play an important role in several diseases, including ST-segment elevation myocardial infarction (STEMI), deep vein thrombosis (DVT) and pulmonary embolism (PE), ischemic stroke, and peripheral arterial disease. Thrombolytic therapy has evolved into an alternative treatment for STEMI, reserved predominantly for patients who do not have access to timely percutaneous coronary intervention. In patients with DVT/PE or arterial related critical limb ischemia, the use of thrombolytic therapy is limited to specific patient populations. Thrombolytic therapy is the treatment of choice for ischemic stroke in patients who present <or=3 hours following the onset of symptoms. Moreover, thrombolytic therapy is used to restore function to stenotized central venous access devices as well as occluded hemodialysis access grafts.
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PMID:Recombinant peptides in thrombolysis. 2063 50


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