重组链激酶在脑内血肿动物模型中的局部应用

观察重组链激酶对人凝血块的溶化作用及对脑组织的毒性反应。分别用重组链激酶（实验组）和生理盐水（对照组）注入人凝血块制成的猫额叶脑内血肿内，观察血肿溶化效果。结果：实验组１０例中６例血肿完全溶化，对照组１０例血肿均未溶化。病理组织学观察，实验组血肿周围脑组织病理改变轻于对照组。结论：重组链激酶对动物模型脑内血肿局部应用有良好的溶化人凝血块的作用，而对周围脑组织无毒性反应。     

Inhibition of pulmonary tumor seeding by antiplatelet and fibrinolytic therapy in an animal experimental model

Fibrin and platelets contribute to the development of blood borne metastases by facilitating the arrest of tumor cell emboli in the microcirculation. We have previously demonstrated that the fibrinolytic agent strep-tokinase inhibits pulmonary tumor cell seeding in an animal model. To determine whether this effect was potentiated by antiplatelet therapy, a further study was performed to assess the effect of streptokinase in combination with aspirin in a similar model. The results demonstrated that aspirin did not significantly enhance the antimetastatic effect of streptokinase (median: streptokinase = 60, streptokinase + aspirin = 60.5, P = 0.79, Mann Whitney). In a second series of experiments, the antimetastatic effect of streptokinase was compared with another fibrinolytic agent, human recombinant tissue plasminogen activator (rt-PA). Fibrinolytic doses of streptokinase (30,000 units/kg) and rt-PA (5 mg/kg) significantly reduced pulmonary tumor seeding when compared with controls (median: control = 48, streptokinase = 23, P<0.01, rt-PA = 29, P < 0.001). There was no significant difference in pulmonary tumor seeding between the groups treated with streptokinase and rt-PA (P = 0.56). The clinical implications of these findings are discussed. © Wiley-Liss, Inc.     

Antibodies to the protein core of the small cell lung cancer workshop antigen cluster-w4 and to the leucocyte workshop antigen CD24 recognize the same short protein sequence leucine-alanine-proline.

We recently described the identity of the small cell lung cancer (SCLC) cluster-w4 antigen and the human B cell differentiation marker CD24, a glycosylphosphatidylinositol (GPI)-anchored, highly glycosylated surface molecule of only 31-35 amino acids [15]. The specificities of three anti-cluster-w4 and of eleven anti-CD24 MoAbs have been investigated with respect to their binding capacity to the protein core of cluster-w4/CD24 antigen. Four overlapping peptides spanning this protein core were synthesized. MoAbs shown to bind to two overlapping peptides by antibody binding inhibition using the cluster-w4/CD24-positive SCLC cell line SW2 and by direct peptide binding detected in an ELISA were investigated in more detail. To determine the exact epitopes recognized by these MoAbs, an epitope mapping assay using peptides synthesized onto polyethylene pins was established. The three anti-cluster-w4 MoAbs SWA11, SWA21 and SWA22 and the anti-CD24 MoAbs OKB2 and ALB9 recognized the same short leucine-alanine-proline (LAP) sequence in an area without potential glycosylation sites close to the GPI anchor of the protein core of the cluster-w4/CD24 antigen.     

注射用基因工程链激酶的临床药物动力学

目的:测定注射用基因工程(重组)链激酶(r-SK)在人体内的药物动力学.方法:6例急性心肌梗死患者在60min期间静脉匀速滴注r-SK 150万IU,用纤维蛋白-凝胶板方法测定血浆中r-SK的活性.结果:血浆浓度-时间曲线以一室模型拟合,Ke:(0.015±0.06 3)1/min,T_1/2:(49.57±19.70)mim;表观分布客积V:(11 637.03±9 730.24)ml;AUC:(18 198.82±16 413.74)IU·min/ml,CL:(153.96±103.09)ml/min.结论:对于治疗急性心肌梗死1h内静脉输注150万IU的r-SK是合适的.     

Improved reperfusion and clinical outcome with enoxaparin as an adjunct to streptokinase thrombolysis in acute myocardial infarction. The AMI-SK study.

AIMS: To establish whether the addition of enoxaparin (a low-molecular-weight heparin) to streptokinase therapy improves early and sustained coronary patency and clinical outcome in patients with evolving myocardial infarction. METHODS AND RESULTS: A total of 496 patients with acute myocardial infarction treated with streptokinase were randomized to an intravenous bolus (30 mg) and subcutaneous injections (1mg x kg(-1), twice daily) of enoxaparin (n=253), or placebo (n=243) for 3-8 days. The median duration of treatment in both groups was 5 days. ST-segment resolution at 90 min and 180 min measured by electrocardiogram was improved in patients receiving enoxaparin. Complete, partial and no ST-segment resolution at 180 min was observed in 36%, 44% and 19% in the enoxaparin group vs 25%, 44% and 31% in the placebo group, respectively (P=0.004). Assessment of the primary end-point revealed improved TIMI-3 flow with enoxaparin vs placebo (70% vs 58%, P=0.01). Combined TIMI-2 and -3 flow was also improved (88% vs 72%, P=0.001), as was TIMI frame count (P=0.003). The triple clinical end-point of death, reinfarction and recurrent angina at 30 days was reduced with enoxaparin (13% vs 21%, P=0.03). CONCLUSION: Streptokinase in combination with enoxaparin is associated with better ST-segment resolution and better angiographic patency at days 5-10, suggesting more effective reperfusion. This was associated with a significant reduction in clinical events, indicating less reocclusion.     

Thrombolytic therapy for acute myocardial infarction: evaluation of a selective approach to invasive diagnosis and therapy in a community hospital

To investigate the effectiveness of selective catheterization and revascularization after thrombolytic therapy for myocardial infarction, we studied the early and late clinical course of 100 consecutive patients treated with streptokinase and an intensive medical regimen. Catheterization was performed because of recurrent angina or evidence for reperfusion and myocardial salvage. Fifty-six patients were catheterized, and 37 underwent revascularization. Hospital mortality was 8%. Among the 92 hospital survivors, after 1 year follow-up there was no significant difference between the revascularized and nonrevascularized groups in total survival (97% and 100%, respectively) or in infarct-free survival (97% and 95%, respectively). During total follow-up of 34 (+/- 13) months, late clinical events (death, reinfarction, late revascularization, and severe angina) occurred in 16% of 37 revascularized patients and in 27% of 55 patients not revascularized (p = 0.31). Cumulative hospital and late survival for the entire group was 91% at 1 year and 86% at final evaluation. Excellent long-term survival and a low incidence of recurrent infarction may be achieved after thrombolytic therapy, using selective catheterization and revascularization based on widely available clinical estimates of further ischemic risk.     

Early results of low dose intra-arterial streptokinase therapy in acute and subacute lower limb arterial ischaemia

Thirty-two patients with acute and subacute limb-threatening peripheral arterial ischaemia were treated with low dose intra-arterial streptokinase infusions. The mean duration of infusion was 38 h. Six patients developed pericatheter thrombosis and two had distal embolization of fragments of thrombus but in all cases these responded to repositioning the catheter and continuing the infusion. Five patients developed groin haematomata and in three of these there was evidence of a systemic fibrinolytic effect from the streptokinase with plasma fibrinogen reduced below 1 g/l. The most serious complication was perforation of the popliteal and tibial arteries which occurred on two occasions and required cessation of the infusion. Twenty-two patients (69 per cent) achieved limb salvage, eight (25 per cent) suffered a major amputation and two (6 per cent) died. The outcome was not related to the site, nature or duration of the arterial occlusion but patients with loss of sensation or paralysis of the affected limb were significantly less likely to obtain limb salvage (P = 0.001). For occlusions greater than 30 cm in length a new technique was used where the thrombus was lysed from distal to proximal in short lengths by gradual catheter withdrawal. This was successful in five out of six cases. Low dose intra-arterial streptokinase has been confirmed as an effective, relatively safe method of treatment in recent arterial ischaemia and can be recommended in situations where the results of surgery may not be favourable. In particular, patients with arterial thromboses and no distal run-off, distal and late arterial emboli, thrombosed popliteal aneurysms and patients after a failed embolectomy, have all been shown to respond to thrombolytic therapy with intra-arterial streptokinase.     

Daily serial evaluation of left ventricular function with equilibrium radionuclide ventriculography following thrombolysis during acute myocardial infarction

The changes in ventricular function after reperfusion by coronary thrombolysis are important when deciding about further definitive treatment necessary to ensure long-term vessel patency. The purpose of this study was to evaluate the early changes in left ventricular function after reperfusion. Left ventricular function was serially evaluated for 10 days in a group of 18 patients receiving intracoronary thrombolytic therapy for an acute myocardial infarction. Comparison of the global ventricular function in the successfully and unsuccessfully reperfused groups of patients showed significantly better function in the successful group than the unsuccessful group after the first day, which was maintained for the entire study period. Global and regional ventricular function in the successfully reperfused patients showed significant early improvement during the initial 72 h with maintenance of this improvement for the study period of 10 days. In the patients in whom reperfusion was unsuccessful, regional ventricular function showed no change, while the global function declined from day 5 to day 8 of the study period. This study then confirms the significant improvement in ventricular function after successful reperfusion. The time course pattern of the change in ventricular function indicates that the most significant improvement occurs within the first 72 h after reperfusion. These changes are similar to those previously reported in experimental animals.     

重组链激酶早期应用对脑出血血肿周围脑组织的影响

目的　研究重组链激酶早期应用对脑出血 (ICH)血肿周围脑组织的影响。方法　 72只SD雄性大鼠制成ICH模型 ,随机分为对照组、重组链激酶组、水蛭素组 ,各组分别在ICH后 4、8、12、16h于血肿腔中注入生理盐水、重组链激酶、或重组链激酶加水蛭素。ICH后 2 4h处死大鼠 ,观察脑组织中的含水量、Na+、K+以及血脑屏障通透性的变化。结果　在ICH后 4、8、12、16h应用重组链激酶 ,可引起脑组织含水量增加以及Na+升高、K+的降低 (P <0 .0 5 ) ,在ICH后 4、8、12h应用重组链激酶 ,脑组织中伊文思蓝 (Evensblue,EB)含量明显升高(P <0 .0 5 )。如同时加用水蛭素 ,与对照组比较脑组织的含水量在 4、8、12h明显降低 (P <0 .0 5 ) ,而脑组织中EB含量则在 4、8、12、16h明显降低 (P <0 .0 5 )。结论　ICH血肿腔中早期应用重组链激酶可加重ICH血肿周围脑组织的损伤 ,联合应用水蛭素不但可防治重组链激酶溶化血块时对脑组织的损伤 ,而且还可降低血肿本身所释放的毒性物质所引起的脑水肿及血脑屏障的破坏