PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “STREPTOKINASE”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 73 records · Page 4Linked to original sources
PubMed1988

Immediate PTCA after successful thrombolysis with intracoronary streptokinase, three years follow-up. A matched pair analysis of the effect of PTCA in the randomized multicentre trial of intracoronary streptokinase, conducted by the Interuniversity Cardiology Institute of The Netherlands.

Immediate PTCA following thrombolysis with streptokinase was performed in 46 out of 533 patients enrolled in a multicentre randomized trial of early reperfusion in patients with acute myocardial infarction. Additional effects of PTCA in patients with a residual diameter stenosis in the infarct-related coronary artery of 70% or more after thrombolysis were compared with successful thrombolysis alone in a matched pair analysis. Thirty six pairs of patients were formed identical with respect to the infarct related coronary artery, presence or absence of previous myocardial infarction, total ST segment elevation on the ECG at admission to the trial, and delay between onset of symptoms and hospital admission. PTCA after thrombolysis did not lead to additional limitation of infarct size, nor to further preservation of left ventricular function. Infarction rate during the three-year follow-up was 14% after PTCA versus 30% after thrombolysis alone (P = 0.05). Similarly, patients had less angina or heart failure after PTCA, since on average 128 out of 156 weeks follow-up were symptom free, while this was only 102 weeks after thrombolysis alone (P = 0.03). Immediate PTCA after thrombolysis with intracoronary streptokinase seems to prevent recurrent ischemia and reinfarction. Further studies should address the proper indication and timing of PTCA after thrombolysis.

Angioplasty, Balloon↗
PubMed2003

Clinical usefulness of a functional test of neutralising streptokinase antibodies for the prediction of the thrombolytic effect of streptokinase in acute myocardial infarction.

We investigated whether the occurrence of neutralising streptokinase (SK) antibodies, as assessed by a new bedside test, was related to the effect of SK in acute myocardial infarction (AMI), assessed with continuous vectorcardiography (VCG). Twenty-eight patients with ST elevation, admitted </= 6 h after the onset of symptoms, treated with 1.5 MIU SK were included. The level of SK antibodies was assessed by the TAS Streptokinase Test Panel, measuring the lysis time of clotted fibrin in the sample. Clot lysis time was negatively correlated to ST vector magnitude (ST-VM) recovery at 90 min (r(S) = -0.40, p = 0.03), and clot lysis time was positively correlated to time to reperfusion, (r(S) = 0.42, p = 0.03). The predictive values of the test, however, were low. In conclusion, as the prediction of reperfusion in AMI after SK by the new test was poor, we cannot recommend it for clinical decision-making prior to the choice of the thrombolytic agent.

Aged↗
PubMed1998

Streptokinase in acute stroke: effect on reperfusion and recanalization. Australian Streptokinase Trial Study Group.

The Australian Streptokinase Trial was a randomized, double-blind, placebo-controlled trial, in which streptokinase (SK, 1.5 million IU I.V.) was given within 4 hours of stroke onset. In a subset of 37 patients, 99mTc-labeled D,L-hexamethylpropylene amine oxime single-photon emission computed tomography (SPECT) and/or transcranial Doppler (TCD) studies were performed before and after therapy to test the hypothesis that SK may improve the hemodynamic measures of reperfusion/recanalization rates (TCD parameter) within 24 hours. Eighteen patients received SK and 19 placebo. Baseline characteristics were similar in both groups, and there were no differences in clinical outcomes assessed at 3 months after stroke. Although there was no increase in the group mean perfusion defect or volume on SPECT after thrombolytic therapy, a larger number of patients demonstrating the combined end point of reperfusion or recanalization was seen in the SK group (13/14, 93%) than in the placebo group (7/14, 50%; p = 0.01). Although SK given within 4 hours of acute ischemic stroke appears to improve arterial patency/tissue reperfusion, this effect is neither early nor extensive enough to influence overall clinical outcome.

Acute Disease↗
PubMed1987

Comparative tolerance and complications in a multicentre trial of intracoronary streptokinase and intravenous anisoylated plasminogen streptokinase activator complex in acute myocardial infarction.

The safety and tolerance data of the preliminary results of a randomised, parallel group, multicentre trial of intracoronary streptokinase and intravenous anisoylated plasminogen streptokinase activator complex (APSAC) in patients with myocardial infarction are presented. The frequency of side effects was similar in the 2 groups. The most frequently encountered side effect was bleeding, overwhelmingly from the groin puncture site from angiography. There was no significant difference between amount or incidence of bleeding complications between the two groups, as measured by number of bleeding episodes, transfusion requirements, or mean drop in haematocrit or haemoglobin.

Anistreplase↗
PubMed1999

Mapping of the antigenic regions of streptokinase in humans after streptokinase therapy.

Streptokinase (SK) is efficaciously used as a thrombolytic drug for the treatment of myocardial infarction. Being a bacterial protein, SK is immunogenic in humans. Therefore, resulting from SK therapy, patients become immunized and anti-SK antibody (Ab) titers rise post-treatment. High Ab titers might provoke severe immune reactions during SK therapy and neutralize SK activity, preventing effective thrombolysis. Spot synthesis combined with peptide library techniques is a useful tool for studying protein-peptide interactions on continuous cellulose membranes. Here, we report on the mapping of antigenic regions of SK using a spot-synthesized peptide library and human total sera from patients receiving SK therapy. All tested samples have high anti-SK Ab titers and most of them show significant SK neutralizing capacity. Individual variations in peptide recognition were detected. However, patients treated with SK tend, in general, to show a common regional binding pattern, including residues 1-20, 130-149, 170-189, and 390-399. This is the first study reporting the probing of a cellulose-bound set of peptides with total human sera.

Amino Acid Sequence↗
PubMed2002

The effect of streptokinase neutralizing antibodies on fibrinolytic activity and reperfusion following streptokinase treatment in acute myocardial infarction.

OBJECTIVES: To evaluate tissue plasminogen activator (tPA) activity as a measure of fibrinolytic response to treatment with streptokinase (SK) and to relate this to the effect of pretreatment SK antibodies and to successful reperfusion assessed by continuous computerized vectorcardiography (VCG). SETTING: Umeå University Hospital. SUBJECTS: A total of 104 patients with acute myocardial infarction (AMI) treated with SK and no history of previous SK treatment were studied. The tPA activity was measured 4 h after the start of treatment. The effect of pre-existing neutralizing antibodies to SK was analysed with a functional assay in pretreatment samples. Reperfusion was evaluated with VCG. MAIN OUTCOME MEASURES: Successful reperfusion. RESULTS: Fifty-five patients (53%) were classified as successfully reperfused. The risk for failed reperfusion was calculated in logistic regression models. In a univariate model, a borderline significant increase in the risk of failed reperfusion was observed in intermediate levels of SK neutralizing antibodies, but not in the highest levels. In a multivariate model, only high tPA activity, >25 U mL(-1), at 4 h (OR 0.17: 95% CI: 0.06-0.51) was associated with a higher rate of reperfusion whilst longer time to treatment (OR 1.17; 95% CI: 1.02-1.35) was associated with a higher risk of failed reperfusion. There was no significant correlation between neutralizing antibodies to SK and tPA activity at 4 h. CONCLUSION: The SK treatment of AMI induced high levels of tPA activity which were associated with successful reperfusion. The effect of pre-existing SK antibodies had no significant influence on reperfusion and were not correlated to the fibrinolytic activity obtained.

Aged↗
PubMed1995

Interaction of streptokinase and plasminogen. Studied with truncated streptokinase peptides.

The interaction of streptokinase (SK) with human plasminogen (HPlg) was investigated using truncated SK peptides prepared by gene cloning techniques. SK(16-414) and SK(16-378) could activate HPlg as efficiently as the authentic SK. SK(60-414), which had been preincubated with SK(1-59), could also activate HPlg. SK(91-414), SK(127-414), and SK(158-414), at a concentration of one-tenth of HPlg, all failed to activate HPlg. However, the truncated SK peptides in complexes with equimolar HPlg could form amidolytically active virgin enzymes that slowly converted to human plasmin (HPlm) after a lag period of 15 min. SK(16-316) could not activate HPlg. No virgin enzyme was detected when SK(16-316) was incubated with equimolar HPlg, but the HPlg in the complex was modified to HPlm after reaction for 20 min. SK(220-414) and SK(16-251) had no ability to transform HPlg to virgin enzyme or to HPlm in equimolar complex with HPlg, although they could bind to HPlg. The functions of five regions in the SK molecule (a, Ile1-Lys59; b, Ser60-Asn90; c, Val158-Arg219; d, Tyr252-Ala316; e, Ser317-Ala378) in interaction with HPlg are deduced. Region a is important in stabilizing the conformation of the SK molecule, and region b is essential for HPlg activation. Region c is required for induction of the conformational changes of HPlg to virgin enzyme. Regions c and d are required for the conversion of HPlg to HPlm in the HPlg.SK equimolar complex. Coordination of regions c, d, and e of SK is essential for a virgin enzyme formation, and coordination of regions b, c, d and e is required for an effective SK-type HPlg activator.

Base Sequence↗
PubMed2004

Role of the streptokinase alpha-domain in the interactions of streptokinase with plasminogen and plasmin.

The role of the streptokinase (SK) alpha-domain in plasminogen (Pg) and plasmin (Pm) interactions was investigated in quantitative binding studies employing active site fluorescein-labeled [Glu]Pg, [Lys]Pg, and [Lys]Pm, and the SK truncation mutants, SK-(55-414), SK-(70-414), and SK-(152-414). Lysine binding site (LBS)-dependent and -independent binding were resolved from the effects of the lysine analog, 6-aminohexanoic acid. The mutants bound indistinguishably, consistent with unfolding of the alpha-domain on deletion of SK-(1-54). The affinity of SK for [Glu]Pg was LBS-independent, and although [Lys]Pg affinity was enhanced 13-fold by LBS interactions, the LBS-independent free energy contributions were indistinguishable. alpha-Domain truncation reduced the affinity of SK for [Glu]Pg 2-7-fold and [Lys]Pg </=2-fold, but surprisingly, rendered both interactions near totally LBS-dependent. The LBS-independent affinity of SK for [Lys]Pm, 3000-fold higher compared with [Lys]Pg, was reduced dramatically by alpha-domain truncation. Thermodynamic analysis demonstrates that the SK alpha-domain contributes substantially to affinity for all Pg/Pm species solely through LBS-independent interactions, and that the higher affinity of SK for [Lys]Pm compared with [Lys]Pg involves all three SK domains. The residual affinity of the SK betagamma-fragment for all Pg/Pm species was increased by an enhanced contribution to complex stability from LBS-dependent interactions or free energy coupling between LBS-dependent and -independent interactions. Redistribution of the free energy contributions accompanying alpha-domain truncation demonstrates the interdependence of SK domains in stabilizing the SK-Pg/Pm complexes. The flexible segments connecting the SK alpha, beta, and gamma domains allow their rearrangement into a distinctly different bound conformation accompanying loss of the constraint imposed by interactions of the alpha-domain.

Aminocaproic Acid↗
PubMed2003

Plasminogen enhances virulence of group A streptococci by streptokinase-dependent and streptokinase-independent mechanisms.

Interactions between host plasminogen (Plg) and streptokinase (SK) secreted by group A streptococci (GAS) have been hypothesized to promote bacterial invasion of tissues. The virulence of GAS strain UMAA2616, after being subcutaneously inoculated into mice, was studied. Skin lesions and mortality were observed after inoculation of 7x106 cfu. Coadministration of human Plg with UMAA2616 markedly increased virulence. SK-deficient UMAA2616 (UMAA2616-SK(-)) was generated. Mean skin-lesion area and mortality, after bacterial inoculation (3x105 cfu), were significantly greater with UMAA2616 in the presence of human Plg than with UMAA2616-SK(-) in the presence of human Plg (P=.0001). Human Plg also enhanced UMAA2616-SK(-) virulence. Exogenous human Plg enhanced the virulence of MGAS166, a human clinical isolate. These findings suggest that SK-Plg interactions are an important determinant of GAS invasiveness in vivo and that both SK and host Plg activators appear to promote virulence of GAS by catalyzing plasmin formation.

Animals↗
PubMed1999

Platelet reactivity and streptokinase resistance following antecedent streptokinase therapy for myocardial infarction.

AIMS: To assess the efficacy of second-time administration of streptokinase (SK). First-time thrombolysis with SK in myocardial infarction (MI) is established but the efficacy of subsequent SK is unknown. METHODS AND RESULTS: Platelet reactivity to shear stress, spontaneous and SK-induced thrombolysis were measured in vitro in 28 patients who had received SK for MI and compared to 15 controls. SK antibody (Ab) titres were inversely related to time from MI. Platelet reactivity was greatly enhanced in patients (p < 0.0001). Spontaneous thrombolysis in patients was poor and in 17 failed to occur. In contrast, thrombolysis occurred in all but 1 control. In patients platelet reactivity was strongly related to thrombolytic activity (r = -0.516; p = 0.0029). SK in vitro was at least 4 times more effective in controls than in patients. CONCLUSION: The chances of achieving patency with second administration of SK are poor. Ab titre is not a reliable predictor of resistance.

Adult↗
PubMed1987

High-dose systemic streptokinase and acylated streptokinase-plasminogen complex (BRL 26921) in acute myocardial infarction: alterations of the fibrinolytic system and clearance of fibrinolytic activity.

We report the results of two consecutive studies using intravenous bolus injections of streptokinase (SK) or acylated plasminogen-SK complex (BRL 26921) in patients with acute myocardial infarction (AMI). In the first study, 20 patients received either 750,000 units (U) SK (group IA, n = 10) or 1,500,000 U SK (group IB, n = 10) within 5-10 min intravenously. In the second study 10 consecutive patients received 750,000 U SK within 15 min (group IIA) intravenously. The following 10 consecutive patients received 30 mg BRL 26921 within 2 min (group IIB). Early reperfusion was found in 16 patients in the first study (8 in each group) and in 18 patients in the second study (9 in each group). The decrease of fibrinolytic activity was biphasic with a half-disappearance time of 112.5 min for BRL 26921 and 31 (IA) and 18 (IB) min for SK. alpha 2-Antiplasmin depletion and a decrease of fibrinogen was observed with no differences after bolus injections of SK and of BRL 26921.

Aged↗
PubMedDate not supplied

[Degradation of streptokinase and the catalytic properties of the plasmin-streptokinase complex].

Streptokinase (SK) interacts with human plasminogen (Pg) or plasmin (Pm) with formation of Pg-SK or Pm-SK complex. Pm-SK complex manifests a fibrinolytic, amidolytic and Pg activator activity. SK in complex with Pm isn't stable and so capable to be hydrolysed rapidly. We investigated a correlation between molecular form of SK and catalytic properties of equimolar Pm-SK complex during preincubation at 20 degrees C. It was found out that amidolytic activity of Pm-SK complex was not changing for 5 hours and decreased to the initial Pm value after 24 hours. During this time alpha 2-antiplasmin (alpha 2-AP) has any effect on amidolytic activity of the complex. Fibrinolytic activity of Pm-SK complex makes up 20% of the initial Pm value and wasn't changing within the investigated period. Pg activator activity was decreasing rapidly to 30-40% of the initial one within few minutes from the moment of Pm-SK complex formation. It was 10-20% of that initial after 24 hours. The decrease in Pg activator activity of Pm-SK complex correlated with the initial very rapid conversion of 47 kDa SK to 36 kDa SK within few minutes and following more slow conversion of SK in 31, 25 and 15 kDa fragments after 5 hours. alpha 2-AP didn't influence on the Pg activator activity of Pm-SK complex but eliminated its fibrinolytic activity completely. It was supposed that alpha 2-AP inhibited fibrinolytic activity of Pm-SK complex similarly to 6-aminohexanoic acid by preventing Pm-SK complex binding to fibrin polymer.

Catalysis↗
PubMed1990

Catabolism of streptokinase and polyethylene glycol-streptokinase: evidence for transport of intact forms through the biliary system in the mouse.

The catabolism of streptokinase (SK) and polyethylene glycol derivatives of SK (PEG-SK) were studied in mice. The clearance and catabolism of SK:plasmin (SK:Pm) and PEG-SK:Pm activator complexes were also investigated. Native 125I-SK cleared rapidly (t1/2 = 15 minutes) from the circulation, with the majority of the ligand accumulating in the liver and gastrointestinal (GI) tract and a substantial fraction also localizing in the kidneys. SK, which was removed from the plasma by the liver, was secreted into bile and then the GI tract. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) demonstrated that 125I-SK recovered from liver and bile was homogeneous and of the same molecular weight (mol wt approximately 50,200) as native SK. PEG-125I-SK cleared slowly (t1/2 greater than 200 minutes), with more than 80% of the preparation localizing in liver and GI tract. The PEG-125I-SK secreted into the bile was also intact. The bile containing 125I-SK was incubated with stoichiometric amounts of plasminogen and electrophoresed under nondenaturing conditions. This study demonstrated that the secreted SK was able to form SK:Pg complexes. SDS-PAGE also showed activation of 125I-Pg that was incubated with recovered bile containing the SK. 125I-SK:Pm catabolism was also studied. In these experiments, the mol wt approximately 42,000 fragment obtained when SK is cleaved by plasmin was found in the bile. This fragment of 125I-SK was not recovered as part of a complex with plasmin, consistent with our previous observations that catabolism of SK:Pm involves transfer of the plasmin to plasma proteinase inhibitors while SK is catabolized independently. By contrast, when PEG-125I-SK:Pm was injected into mice, only intact PEG-125I-SK was found in the bile, consistent with our previous observations that the PEG derivatization blocks its degradation by plasmin.

Animals↗
PubMed1993

A functional analysis of the antigenicity of streptokinase using monoclonal antibody mapping and recombinant streptokinase fragments.

Streptokinase (SK), a bacterial product of pathogenic Streptococcus species, is now widely used as an effective therapy for the treatment of heart attacks. Because naturally occurring antibody to SK is ubiquitous, serious allergic reactions to SK therapy are common. To begin to identify regions of the molecule that are important for the antigenicity of SK we performed studies using a panel of 51 hybridomas producing anti-SK antibodies, recombinant SK fragments, and assays of SK activity. Antibodies generated from mice hyperimmunized with wild-type SK were shown to fall into six distinct complementation groups by competitive binding studies. Recombinant SK fragments were used to determine the peptide regions recognized by these complementation groups. Correlation of the effects of the mAb on SK function, with knowledge of their SK fragment-binding pattern, suggested regions of the SK molecule that are important for the construction and the catalytic function of the SK-plasminogen activator complex.

Antibodies, Monoclonal↗
PubMed1997

Clinical trial of China-made recombinant streptokinase in acute myocardial infarction. Collaborative Study Group on Thrombolysis with China-made recombinant streptokinase.

OBJECTIVE: To evaluate the efficacy and safety of intravenous recombinant streptokinase (r-SK), produced in China, in the treatment of acute myocardial infarction (AMI). METHODS: One hundred and seventy-three patients with AMI admitted to seven hospitals from February to October 1995 were conformed to the inclusion and exclusion criteria of thrombolytic therapy. The patients were divided into two groups. One hundred and two patients in the Group A were randomized to receive r-SK (n = 51) or SK (n = 51). Seventy-one patients were treated with r-SK in the Group B. One and half million units of r-SK or SK were given intravenously over 60 minutes and the clinical criteria of reperfusion were evaluated. Coronary angiography was performed 90 minutes after thrombolytic therapy with r-SK in 34 patients and recanalization of infarct-related arteries was determined using the TIMI criteria. RESULTS: The reperfusion rate was 80.4% in 51 patients receiving r-SK and 74.5% in 51 patients receiving SK (P > 0. 05). The total reperfusion rate was 77.1% in 122 patients treated with r-SK. Ninety minutes after the initiation of thrombolytic therapy, the occluded infarct-related arteries were patent in 70. 6% (24/34) of patients treated with r-SK. Chill, hypotension and mild bleeding occurred respectively in 4.1%, 5.7% and 16.4% of patients with r-SK. CONCLUSION: China-made r-SK is a safe and effective thrombolytic agent.

Adult↗
PubMed1997

Signal transduction in the platelet activation induced by IgG anti-streptokinase and anisoylated plasminogen-streptokinase activator complex.

Streptokinase (SK) is one of the plasminogen activators currently used in therapeutics. SK antibodies may appear in the blood after thrombolytic therapy with SK or after-hemolytic streptococci infection. Such antibodies may both activate platelets and neutralize the ability of SK to convert plasminogen into plasmin. We previously demonstrated that platelet activation induced by the combination of IgG anti-SK and anisoylated plasminogen-SK activator complex (APSAC) is mediated by Fc gamma RIIa1 receptor. However, the mechanism by which IgG anti-SK and APSAC (or SK) transduce an activating signal across the platelet plasma membrane remains unknown. We have demonstrated in the present study that the platelet aggregation induced by the combination of IgG anti-SK and APSAC is accompanied by an increase in inositol phosphate, Ca2+ mobilization and thromboxane (Tx) A2 generation. Neomycin, erbstatin and GF 109203X, which inhibit phospholipase C (PLC), protein tyrosine kinase (PTK) and protein kinase C (PKC) activities, respectively, abolished platelet aggregation induced by IgG anti-SK plus APSAC, indicating the pivotal roles of the PLC, PTK and PKC pathways in this immunological activation. In addition, TxA2 generation is also important since aspirin, a cyclooxygenase inhibitor and SQ 29548, a TxA2 receptor antagonist, showed significant inhibition of the platelet response. The contribution of released ADP was confirmed using apyrase, which significantly inhibited IgG anti-SK plus APSAC-induced platelet aggregation. Finally, WEB 2086, a platelet-activating factor (PAF) receptor antagonist, was not effective, indicating that PAF is not involved in this process. APSAC- or SKinduced platelet activation may limit the therapeutic effectiveness of the drug and may contribute to the pathogenesis of early reocclusion. The study of the mechanism leading to APSAC-induced platelet activation could be relevant for a better understanding of the physiopathology of immune complex disorder diseases and thrombolytic treatment failure.

Journal Article↗