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At least 847 records · Page 47Linked to original sources
PubMed1985

Streptokinase in the treatment of acute arterial occlusion of the hand.

Continuous, low-dose, intra-arterial streptokinase was used to treat six patients with ischemia of the hand secondary to distal arterial occlusion. A bolus dose of 100,000 U of streptokinase was administered, followed by a maintenance dose of 5000 U/hr, which was titrated against the patients' coagulation profile. The duration of infusion ranged from 16 to 96 hours. Recanalization was achieved in four patients who were treated within 36 hours of the onset of occlusion.

Acute Disease↗
PubMed1997

Influence of diabetes mellitus on clinical outcome in the thrombolytic era of acute myocardial infarction. GUSTO-I Investigators. Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries.

OBJECTIVES: This study was undertaken to define and better understand the characteristics and outcomes of patients with diabetes treated for acute myocardial infarction with contemporary thrombolysis. BACKGROUND: Although thrombolysis has substantially improved survival of patients with myocardial infarction, diabetes mellitus remains an independent predictor for a poor prognosis. METHODS: We characterized the contemporary relation between diabetes and outcome after myocardial infarction treated with thrombolytic agents from a large international cohort. Of 41,021 patients randomized to receive accelerated tissue-type plasminogen activator (t-PA), streptokinase or a combination of both agents in the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries study, there were 5,944 patients with diabetes and 34,888 patients without diabetes. RESULTS: Patients with diabetes were older and more likely to be female, to present with anterior wall infarction, to receive thrombolysis later and to have triple-vessel coronary artery disease. Mortality at 30 days was highest among diabetic patients treated with insulin (12.5%) compared with non-insulin-treated diabetic (9.7%) and nondiabetic (6.2%) patients (p < 0.001). Mortality was lowest among those with diabetes receiving accelerated t-PA, which is consistent with the results of the overall patient cohort. Although stroke occurred more frequently among diabetic (1.9%) than nondiabetic patients (1.4%, p < 0.001), there was no significant difference in the rates of intracranial hemorrhage. Cardiac failure, shock, atrioventricular block and atrial flutter/ fibrillation were more common among diabetic patients. The proportion of patients undergoing revascularization was similar between patients with and without diabetes, although diabetic patients were more likely to undergo coronary artery bypass graft surgery (10.4% vs. 8.3%). Diabetes remained an independent predictor for mortality at 1-year follow-up (14.5% vs. 8.9%, p < 0.001). CONCLUSIONS: Diabetes, alone and in association with its comorbidities, portends a substantially worse 30-day and 1-year prognosis for patients with myocardial infarction.

Aged↗
PubMed1998

Efficacy of streptokinase, but not tissue-type plasminogen activator, in achieving 90-minute patency after thrombolysis for acute myocardial infarction decreases with time to treatment. PERM Study Group. Prospective Evaluation of Reperfusion Markers.

OBJECTIVES: We sought to examine the relation between time to treatment and 90-min patency rates in patients receiving intravenous streptokinase (SK) or accelerated tissue-type plasminogen activator (t-PA). BACKGROUND: Early patency of the infarct-related artery is a major determinant of survival after thrombolysis for acute myocardial infarction. Some data suggest that time to treatment may influence the efficacy of nonfibrin-specific thrombolytic agents in restoring early patency of the infarct-related vessel. METHODS: We performed a retrospective analysis of a cohort of 481 patients receiving thrombolytic therapy for acute myocardial infarction <6 h after pain onset, all of whom underwent 90-min coronary angiography. Patency of the infarct-related artery was graded by two observers who had no knowledge of the treatment received or the time between pain and therapy. RESULTS: There was no difference in baseline clinical or angiographic characteristics according to the timing or nature of treatment. Thrombolysis in Myocardial Infarction (TIMI) flow grade 2 or 3 patency rate after SK correlated negatively with the time between onset of pain and thrombolysis (r = 0.8, p = 0.05), whereas the 90-min patency rate after t-PA appeared stable as a function of time to treatment. When patients were categorized as having received treatment <3 or > or = 3 h after pain onset, the patency rate was similar with t-PA, but significantly higher when SK was administered early rather than late, regardless of whether TIMI flow grades 2 and 3 were pooled (86.9% vs. 59.4%, p = 0.0001) or TIMI flow grade 3 alone was considered to indicate patency (81.7% vs. 53.6%, p = 0.0001). Multivariate logistic regression analysis showed a negative effect of time to treatment on the patency probability for SK (p = 0.0001) but not for t-PA. CONCLUSIONS: The efficacy of streptokinase but not t-PA in restoring early coronary patency after intravenous thrombolysis is markedly lower when patients are treated later after onset of pain.

Coronary Angiography↗
PubMed1994

Combined treatment with antibiotic, heparin and streptokinase--a new approach to the therapy of bacterial osteomyelitis.

Combined treatment by continuous intravenous infusion of a selected antibiotic and heparin and/or streptokinase was elaborated as a method of causal, systemic treatment of bacterial osteomyelitis. The aim of the combined treatment was to overcome infection and disturbances in the coagulation and fibrinolysis system which lead to impairment of the bone blood supply and its subsequent necrosis as the main factor in the aetiopathology of osteomyelitis. Between 1969 and 1991, combined treatment was introduced in 63 patients with acute onset disease or with chronic osteomyelitis. Osteomyelitis was located in the mandible in 38 patients and in the long bones in 14 patients. Prior to combined treatment, moderate bone surgery was performed in 21 patients, while 31 patients were excluded from surgery. Combined treatment with an antibiotic and heparin (A+H) was performed in 43 patients, and the other 6 patients had infusion of an antibiotic, streptokinase and heparin (A+S+H). The authors' method of combined treatment offers a new approach and an alternative to routinely-ordered antibiotic therapy and radical surgery, which allow frequent recurrences of the disease, a long-lasting course and severe complications.

Adolescent↗
PubMed1984

Hydrodynamic studies on the streptokinase complexes of human plasminogen, Val442-plasminogen, plasmin, and the plasmin-derived light (B) chain.

Sedimentation velocity and sedimentation equilibrium studies have been carried out on the Glu- and Lys-plasminogen-streptokinase complexes as well as on the complexes formed by Val442-plasmin and the light (B) chain of plasmin. Sedimentation equilibrium molecular weights are consistent with a 1 to 1 molar complex in all cases and give values consistent with the differences in size of the plasminogen moieties. Sedimentation velocity determinations in the presence of protease inhibitors give values consistent with the conformational differences already reported for the Glu- and Lys-plasminogen molecules. However, unlike Glu-plasminogen, the addition of epsilon-aminocaproic acid or lysine does not alter the conformation of the Glu-plasminogen complex. The values of the sedimentation coefficient and the molecular weight of the plasmin and the Val442-plasmin-streptokinase complexes increase to those of a dimer when determined in the absence of active-site inhibitors but return to monomer values when these inhibitors are added. Thus, dimer formation requires the presence of an available active site in at least one of the two molecules involved and is reversible.

Fibrinolysin↗
PubMed2000

Kinetic and structural characterization of a two-domain streptokinase: dissection of domain functionality.

The mammalian protease plasminogen can be activated by bacterial activators, the three-domain (alpha, beta, gamma) streptokinases and the one-domain (alpha) staphylokinases. These activators act as plasmin(ogen) cofactors, and the resulting complexes initiate proteolytic activity of host plasminogen which facilitates bacterial colonization of the host organism. We have investigated the kinetic mechanism of the plasminogen activation mediated by a novel two-domain (alpha, beta) streptokinase isolated from Streptococcus uberis (Sk(U)) with specificity toward bovine plasminogen. The interaction between Sk(U) and plasminogen occurred in two steps: (1) rapid association of the proteins and (2) slow transition to the active complex Sk(U)-PgA. The complex Sk(U)-PgA converted plasminogen to plasmin with the following parameters: K(m) < or = 1.5 microM and k(cat) = 0.55 s(-)(1). The ability of proteolytic fragments of Sk(U) to activate plasminogen was investigated. Only two C-terminal segments (97-261 and 123-261), which both contain the beta-domain (126-261), were shown to be active. They initiated plasminogen activation in complex with plasmin, but not with plasminogen, and thereby exhibited functional similarity to the staphylokinase. The fusion protein His(6)-Sk(U) (i.e., Sk(U) with a small N-terminal tag) acted exclusively in complex with plasmin as well. These observations demonstrate that (1) the N-terminal alpha-domain, including a native N-terminus, was necessary for "virgin" activation of the associated plasminogen in the Sk(U)-PgA complex and (2) the C-terminal beta-domain of Sk(U) is important for recognition of the substrate in the Sk(U)-PgA complex.

Animals↗
PubMed2001

Multidomain structure of a recombinant streptokinase. A differential scanning calorimetry study.

The temperature dependence of the heat capacity function of a recombinant streptokinase (rSK) has been studied by high-sensitivity differential scanning microcalorimetry and circular dichroism as a function of pH in low- and high-ionic strength buffers. At low ionic strength it is found that this protein, between pH 7 and 10, undergoes four reversible and independent two-state transitions during its unfolding, suggesting the existence of four domains in the native structure of the protein. This result reconciles previous conflicting reports about the number of domains of this protein obtained by differential scanning calorimetry and small-angle X-ray scattering. The number of two-state transitions decreases when the pH of the medium is decreased, without noticeable changes in its circular dichroism spectrum. A plausible localization of the four domains in the streptokinase sequences is proposed and their thermodynamic parameters are given. Increase of ionic strength to 200 mM NaCl affects positively the protein stability and confirms the existence of four reversible two-state transitions. Above 200 mM NaCl the protein stability decreases, resulting in low percentage of reversibility, and even irreversible transitions.

Calorimetry, Differential Scanning↗
PubMed2004

Profiling the immune responses of human patients treated with recombinant streptokinase after myocardial infarct.

The SPOT synthesis of peptide arrays on continuous cellulose membranes should be generally applicable in the analysis of sequential antibody binding sites using the enzyme-substrate or other standard detection protocols. The use of total serum is limited by the occurrence of high background levels. This may be overcome if affinity purified antibodies or sera with high antibody titers are used, which allows work at high dilutions and a consequent reduction of background level. Here we demonstrate the mapping of antigenic regions located on recombinant streptokinase SK-2 (Heberkinase) using cellulose-bound peptide scans and human total sera from patients treated with SK-2 (Heberkinase). Streptokinase (SK) is a 47 kDa protein produced by various strains of hemolytic streptococci and is a potent activator of the fibrinolytic enzyme system in humans. SK is in widespread clinical use to treat acute infarction because of its function as an activator of vascular fibrinolysis. Since streptococcal infections are common, normal individuals are immunized with SK and antibodies (Abs) to SK can be detected in most of them. This therapy generates significant T-cell responses to SK and the neutralizing capacity of the Abs rises significantly. Neutralizing Abs reduces the efficiency of thrombolytic therapy and may cause allergic reactions. The widespread use of SK in humans makes its antigenicity an important clinical problem. In this regard the study of the immunodominant regions of SK becomes an important aspect for the improvement of this thrombolytic agent.

Amino Acid Sequence↗
PubMed1996

Dissolution of pseudophakic fibrinous exudate with intraocular streptokinase.

A fibrinous exudate developed in 8 children after cataract extraction. Blunt trauma was the cause of cataract formation in 6 children; the other 2 presented with congenital cataract. In 4 of 6 children with traumatic cataract, iris damage was evident. Seven children had an intraocular lens implanted. The development of fibrinous exudate in the anterior chamber was noted despite routine post-operative topically administered steroids. It typically formed 1-4 days after surgery. In all cases topical fortified steroids were unsuccessful in hastening dissolution. Intracameral injection of streptokinase (500-1000 IU) caused dissolution of fibrin in all cases. No adverse effects were apparent clinically with intraocular administration of streptokinase.

Adolescent↗
PubMed1992

High level expression of streptokinase in Escherichia coli.

Streptokinase (SK), which activates human plasminogen by promoting its conversion to plasmin, is normally obtained from beta-hemolytic streptococci. Treatment with SK is an effective therapy for improving survival and preserving left ventricular function after coronary thrombosis. We report the cloning, expression in E. coli to levels of 25% of the total cell protein, and characterization of a novel SK (SKC-2) gene, the product of which is functionally equivalent to the naturally-derived protein. The availability of a recombinant streptokinase (rSK) in high yield and purity offers a potentially attractive alternative source of this important therapeutic agent.

Amino Acid Sequence↗
PubMed1985

Kinetic studies on the interaction of streptokinase and other plasminogen activators with plasminogen and fibrin.

The activation of Lys-plasminogen to plasmin by streptokinase was promoted by soluble fibrin such that Km was decreased and Vmax. increased. Enhancement was also observed when Glu-plasminogen was the substrate and was shared by the preformed streptokinase-plasminogen activator complex, indicating that the stimulation was not exerted primarily on the rate of active site formation.

Binding Sites↗
PubMed2000

Zymogen activation in the streptokinase-plasminogen complex. Ile1 is required for the formation of a functional active site.

Plasminogen (Plgn) is usually activated by proteolysis of the Arg561-Val562 bond. The amino group of Val562 forms a salt-bridge with Asp740, which triggers a conformational change producing the active protease plasmin (Pm). In contrast, streptokinase (SK) binds to Plgn to produce an initial inactive complex (SK.Plgn) which subsequently rearranges to an active complex (SK.Plgn*) although the Arg561-Val562 bond remains intact. Therefore another residue must substitute for the amino group of Val562 and provide a counterion for Asp740 in this active complex. Two candidates for this counterion have been suggested: Ile1 of streptokinase and Lys698 of Plgn. We have investigated the reaction of SK mutants and variants of the protease domain of microplasminogen (muPlgn) in order to determine if either of these residues is the counterion. The mutation of Ile1 of SK decreases the activity of SK.Plgn* by 100-fold (Ile1Val) to >/= 104-fold (Ile1-->Ala, Gly, Trp or Lys). None of these mutations perturb the binding affinity of SK, which suggests that Ile1 is not required for formation of SK.Plgn but is necessary for SK.Plgn*. The substitution of Lys698 of muPlgn decreases the activity of SK.Plgn* by only 10-60-fold. In contrast with the Ile1 substitutions, the Lys698 mutations also decreased the dissociation constant of the SK complex by 15-50-fold. These observations suggest that Lys698 is involved in formation of the initial SK.Plgn complex. These results support the hypothesis that Ile1 provides the counterion for Asp740.

Binding Sites↗
PubMed2000

Safety and efficacy of eptifibatide vs placebo in patients receiving thrombolytic therapy with streptokinase for acute myocardial infarction; a phase II dose escalation, randomized, double-blind study.

AIMS: Thrombolytic therapy restores coronary patency in patients with acute myocardial infarction, although normal perfusion (TIMI 3 flow) is not achieved in all patients. In an attempt to improve TIMI 3 flow, a combination of full-dose streptokinase, aspirin and escalating dosages of a platelet glycoprotein IIb/IIIa receptor blocker, eptifibatide, vs placebo were tested. METHODS AND RESULTS: A bolus of 180 microg. kg(-1)of eptifibatide was administered in each group, followed by a 72 h continuous infusion of 0.75 (44 patients), 1.33 (n=45) and 2.00 microg. kg(-1). min(-1)(n = 30); 62 patients received placebo. Normal perfusion (TIMI 3 flow) at 90 min was observed in 31% of placebo patients compared to 46, 42 and 45% in the ascending eptifibatide groups (44% for combined eptifibatide groups, P = 0.07). Patency (TIMI 2 and 3 flow combined) increased from 61% (placebo) to 78% for the combined eptifibatide groups (P = 0.02). Reocclusion was infrequent. No differences were observed in TIMI flow grades among eptifibatide groups. Major and minor bleeding was increased and occurred mainly at the arterial puncture site. CONCLUSION: A combination of full dose streptokinase with different eptifibatide regimens enhanced coronary perfusion, but bleeding risk was excessive. Additional trials are needed with different dosage regimens to determine the optimal combination of fibrinolytic agents and platelet glycoprotein IIb/IIIa receptor blockers.

Adult↗
PubMed1977

[Treatment of iliac artery stenosis with low dose streptokinase (author's transl)].

Ten patients with 13 stenoses in the pelvic area were treated with low doses of streptokinase (30 000 U/h) for 72 hours. A significant improvement in the degree of stenosis was obtained as shown by post-stenotic pressure values. Biochemically there was a marked plasminaemia with moderately low fibrinogen levels. Streptokinase treatment with low doses could form an alternative method of treatment in arterial stenoses.

Adult↗
PubMed1975

[Dosage of long-term streptokinase fibrinolytic administration (author's transl)].

Using generalyy accepted dosage schedules during long-term fibrinolytic treatment with streptokinase, anticoagulatory protection against recurrent thromboses can no longer be guaranteed after two to three days, unless heparin is also administered. In contrast, no heparin was needed in 11 out of 13 patients on fibrinolytic treatment of at least five days when maintenance dose was adjusted in accordance with results of coagulation tests. In this way prolonged fibrinolysis was maintained together with adequate anticoagulation by circulating fibrin(ogen) breakdown products for the entire duration of streptokinase treatment. This required the gradual reduction of maintenance dose to between 40 000 U/h and 80 000 U/h in the majority of patients. This form of fibrinolytic treatment with individually adjusted dosages can be undertaken without undue strain on laboratory resources; the risk of haemorrhage is no higher than with the customary form using higher and constant maintenance doses.

Drug Therapy, Combination↗
PubMed1979

[Acute renal failure due to diffuse cholesterol crystal embolisation during streptokinase treatment (author's transl)].

In a 65-year-old man livedo reticularis occurred in the lower half of the body two days after beginning lysis with streptokinase. This was followed by skin and toe necrosis as well as acute renal failure. Autopsy showed a severe ulcerative atherosclerosis of the aorta with cholesterol crystal embolisation in numerous organs, particularly in both kidneys. The coincidence in time leads one to assume that the streptokinase treatment encouraged acute diffuse embolisation by dissolving the protective thrombi over the ulcerative atheromatous plaques.

Acute Kidney Injury↗
PubMed1981

Intrapleural instillation of streptokinase. Effects on systemic fibrinolysis.

Ten consecutive patients aged 25 to 75 with postoperative empyema or hemothorax conventionally treated with drainage without sufficient effect were given intrapleural instillations of streptokinase (Kabikinase, 250,000 IE) for 4 hours). The effects on systemic fibrinolysis were studied. Venous blood samples for determination of fibrinolytic activity on fibrin plates, plasminogen, alpha 2-antiplasmin, alpha 2-macroglobulin, fibrinogen, fibrin(ogen) degradation products (FDP) and thrombin time were taken before instillation, after instillation and then after 24 hours. Preinstillation values were compared to the values 4 and 24 hours after instillation with Student's paired t-test. There were no differences in fibrinolytic activity, alpha 2-macroglobulin and thrombin time. There was a slight increase in plasminogen, alpha 2-antiplasmin and fibrinogen, probably due to an acute phase reaction. Fibrin degradation products showed an increase with border line significance. These changes are not consistent with generalized fibrinolysis, and it is concluded that intrapleural instillations of streptokinase can be given safely in the early posttraumatic or postoperative period.

Adult↗
PubMed1987

Low-dose streptokinase in the treatment of arterial graft occlusions.

During the past 24 months, 19 infrainguinal bypass graft occlusions occurring in 17 patients were treated with local infusions of streptokinase. The treated grafts included three venous femorocrural grafts and four venous and 13 Goretex femoropopliteal grafts. Infusion managed to restore flow completely in 10 grafts. Partial clot lysis occurred in three and no lysis in six grafts. All successful recanalisations occurred within 120 hours of the initiation of thrombolytic therapy. Despite three major complications and the development of two minor haematomas, with an overall success rate of 55% our results support the use of streptokinase in the management of occluded bypass grafts.

Acute Disease↗