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Cardiovascular Therapeutics Apr 2012Coronary artery disease is the single leading cause of death in the United States. Occlusion of the coronary artery was identified to be the cause of myocardial... (Review)
Review
Coronary artery disease is the single leading cause of death in the United States. Occlusion of the coronary artery was identified to be the cause of myocardial infarction almost a century ago. Following a series of investigations, streptokinase was discovered and demonstrated to be beneficial for the treatment of patients with acute myocardial infarction in terms of reducing short- and long-term mortality. Newer agents including tissue plasminogen activators such as alteplase, reteplase, tenecteplase were developed subsequently. In the present era, thrombolytic therapy and primary percutaneous coronary intervention has revolutionized the way patients with acute myocardial infarction are managed resulting in significant reduction in cardiovascular death. This article provides an overview of the various thrombolytic agents utilized in the management of patients with acute myocardial infarction.
Topics: Contraindications; Fibrinolytic Agents; History, 20th Century; Humans; Myocardial Infarction; Plasminogen Activators; Streptokinase; Thrombolytic Therapy
PubMed: 21070617
DOI: 10.1111/j.1755-5922.2010.00239.x -
British Medical Journal Apr 1977
Topics: Humans; Streptokinase; Thromboembolism
PubMed: 851787
DOI: No ID Found -
Polish Journal of Microbiology 2011Application of streptokinase (SK) as a common and cost-effective thrombolytic drug is limited by its antigenicity and undesired hemorrhagic effects. Prior... (Comparative Study)
Comparative Study
Application of streptokinase (SK) as a common and cost-effective thrombolytic drug is limited by its antigenicity and undesired hemorrhagic effects. Prior structural/functional and epitope-mapping studies on SK suggested that removal of 59 N-terminal residues led to its fibrin dependency and identified SK antigenic regions, respectively. Following in silico analyses two truncated SK proteins were designed and compared for their fibrin specificity and antigenicity with the full-length SK. Computer-based modeling was used to predict the effect of vector (pET41a)-born protein tags on the conformation of SK fragments. SK60-386, SK143-386 and full-length SK (1-414) were separately cloned, expressed in BL21 E. coli cells and confirmed by Western-blotting. Functional activity of the purified proteins was evaluated with chromogenic and clot lysis assays and their antigenicity was tested by ELISA assay using rabbit anti-streptokinase antibody. As expected, chromogenic bioassay showed a major activity decline for SK60-386 and SK143-386 (83 and 91 percent, respectively), compared to SK1-414. However, in clot lysis assay, which is a fibrin-dependent pharmacopoeia-approved test, SK60-386 and SK143-386 were respectively 35 and 31 percent more active though lysed the clots slower than full-length SK. Antigenic analysis also indicated significant decrease in ELISA signals obtained for truncated proteins compared to SK1-414 (45 and 28 percent less reactivity for SK143-386 and SK60-386, respectively, p < 0.0001). The results of this study for the first time pointed to SK143-386 and SK60-386, as improved SK derivatives with increased fibrin-selectivity and decreased antigenicity as well as acceptable bioactivity profiles in a pharmacopoeia-based analysis, which deserve more detailed pharmacological studies.
Topics: Amino Acid Sequence; Cloning, Molecular; Models, Molecular; Molecular Sequence Data; Recombinant Proteins; Streptokinase; Structure-Activity Relationship
PubMed: 22184932
DOI: No ID Found -
Proceedings of the Royal Society of... Jul 1964
Topics: Aminocaproates; Aminocaproic Acid; Deoxyribonuclease I; Fibrinolysin; Fibrinolysis; Pharmacology; Physiology; Plasminogen; Pulmonary Embolism; Streptodornase and Streptokinase; Streptokinase; Thrombolytic Therapy; Thrombosis; Vascular Diseases
PubMed: 14178954
DOI: No ID Found -
British Medical Journal Oct 1953
Topics: Deoxyribonuclease I; Hemorrhage; Streptodornase and Streptokinase; Streptokinase; Urinary Retention; Urogenital System
PubMed: 13094068
DOI: No ID Found -
Journal of Clinical Pathology May 1964
Topics: Androgens; Chlorpropamide; Deoxyribonuclease I; Diabetic Angiopathies; Drug Therapy; Fibrinolysin; Niacin; Nicotinic Acids; Pulmonary Embolism; Streptodornase and Streptokinase; Streptokinase; Thrombolytic Therapy; Toxicology; Vascular Diseases
PubMed: 14159477
DOI: 10.1136/jcp.17.3.338 -
Journal of the American College of... Nov 1991The (Thrombolysis in Myocardial Infarction) TIMI-I trial led to the hypothesis that the greater reperfusion rate seen with recombinant tissue-type plasminogen activator...
The (Thrombolysis in Myocardial Infarction) TIMI-I trial led to the hypothesis that the greater reperfusion rate seen with recombinant tissue-type plasminogen activator (rt-PA) versus streptokinase would result in greater reductions in infarct size and mortality in patients with acute myocardial infarction. Despite extensive investigation, no trial comparing rt-PA with streptokinase (European Cooperative Study Group, Plasminogen Activator Italian Multicenter Study [PAIMS], Gruppo Italiano per lo Studio della Sopravvivenze nell'Infarto Miocardico [GISSI-2], International Study on Infarct Survival [ISIS-3], even TIMI-I itself) nor rt-PA and anisoylated plasminogen-streptokinase activator complex (APSAC or anistreplase) (Bassand, TEAM-3, ISIS-3), have confirmed this hypothesis. In a reversal of traditional scientific method, the studies, rather than the unconfirmed hypothesis, have been rejected. A lack of independent review of this subject may have contributed to this outcome. It is proposed that standards of review and editorial comment mandating true critical distance and independence be followed, permitting greater independence of scientific inquiry, review and debate.
Topics: Anistreplase; Aspirin; Heparin; Humans; Myocardial Infarction; Recombinant Proteins; Streptokinase; Thrombolytic Therapy; Tissue Plasminogen Activator
PubMed: 1939963
DOI: 10.1016/0735-1097(91)90692-3 -
Journal of the American College of... Jun 1995Data are now available from three large-scale randomized trials that directly compare the risks and benefits of thrombolytic agents in acute myocardial infarction. In... (Review)
Review
Data are now available from three large-scale randomized trials that directly compare the risks and benefits of thrombolytic agents in acute myocardial infarction. In the interpretation of results from the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI-2) trial and its International Extension, the Third International Study of Infarct Survival (ISIS-3), and the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-1) trial, there are areas of both agreement and controversy. It is generally agreed that the agents most commonly used in the United States--tissue-type plasminogen activator (t-PA), streptokinase and anisoylated plasminogen streptokinase activator complex (APSAC)--all reduce mortality when given to patients with acute evolving myocardial infarction. Further, it is clear that thrombolytic therapy given to such patients presenting up to 12 h after onset of symptoms reduces the mortality rate by approximately 20%, that aspirin therapy for patients presenting up to 24 h reduces the mortality rate by approximately 23% and that the benefits of thrombolytic therapy and aspirin are additive. Finally, and of most importance, the earlier administration as well as the more widespread use of thrombolytic therapy and aspirin would save many more lives. The totality of evidence clearly indicates that streptokinase produces significantly fewer strokes and cerebral hemorrhages than either t-PA or APSAC. Whether or not accelerated t-PA has a small advantage for mortality is less conclusive.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Anistreplase; Aspirin; Cerebrovascular Disorders; Forecasting; Humans; Myocardial Infarction; Randomized Controlled Trials as Topic; Streptokinase; Thrombolytic Therapy; Tissue Plasminogen Activator
PubMed: 7775709
DOI: 10.1016/0735-1097(95)00107-f -
Journal of the American Chemical Society Nov 2018Although the functional specificity and catalytic versatility of enzymes have been exploited in numerous settings, controlling the spatial and temporal activity of...
Although the functional specificity and catalytic versatility of enzymes have been exploited in numerous settings, controlling the spatial and temporal activity of enzymes remains challenging. Here we describe an approach for programming the function of streptokinase (SK), a protein that is clinically used as a blood "clot buster" therapeutic. We show that the fibrinolytic activity resulting from the binding of SK to the plasma proenzyme plasminogen (Pg) can be effectively regulated (turned "OFF" and "ON") by installing an intrasteric regulatory feature using a DNA-linked protease inhibitor modification. We describe the design rationale, synthetic approach, and functional characterization of two generations of intrasterically regulated SK-Pg constructs and demonstrate dose-dependent and sequence-specific temporal control in fibrinolytic activity in response to short predesignated DNA inputs. The studies described establish the feasibility of a new enzyme-programming approach and serves as a step toward advancing a new generation of programmable enzyme therapeutics.
Topics: DNA; Drug Design; Humans; Plasminogen Activators; Protease Inhibitors; Streptokinase
PubMed: 30347143
DOI: 10.1021/jacs.8b10166 -
Journal of Clinical Pharmacology Oct 1987There has been rapid proliferation of understanding and experience with thrombolytic therapy for acute myocardial infarction. Over the last few years, selective... (Clinical Trial)
Clinical Trial Review
There has been rapid proliferation of understanding and experience with thrombolytic therapy for acute myocardial infarction. Over the last few years, selective intracoronary infusion of lytic therapy has been replaced by intravenous administration because of the fundamental importance of time to reperfusion. Newer thrombolytic agents, such as tissue plasminogen activator (t-PA) and acylated streptokinase (APSAC), with properties distinct from streptokinase (SK) and urokinase, have been developed and have undergone extensive clinical trial evaluation. This review will focus primarily on the recent advances in thrombolytic therapy, with particular attention to efficacy, safety, and comparative aspects of the various agents currently or soon to be available.
Topics: Clinical Trials as Topic; Fibrinolytic Agents; Humans; Myocardial Infarction; Recombinant Proteins; Streptokinase; Tissue Plasminogen Activator; United States; United States Food and Drug Administration
PubMed: 3123526
DOI: 10.1002/j.1552-4604.1987.tb02989.x