Objective To assess the effect of different thrombolytic agents, and different regimens in acute ischaemic stroke. Methods A systematic review of all the relevant randomized controlled trials (RCTs) was performed. RCTs were identified from the Cochrane Stroke Group trials register, Embase (1980 to 1997), handsearching Japanese and Chinese journals, and personal contact with pharmaceutical companies. We included randomised and quasi-randomised trials in patients with confirmed acute ischaemic stroke comparing different doses of a thrombolytic agent, or different thrombolytic agent, or the same agent given by different routes. Results Eight trials involving 1 334 patients were included. Concealment of allocation was generally adequate. All the trials were conducted in Japan. Different doses (of tissue plasminogen activator or urokinase) were compared in six trials. Different agents (tissue plasminogen activator versus urokinase,or tissue-cultured urokinase versus conventional urokinase) were compared in three trials. Few data were available for functional outcomes. A higher dose of thrombolytic therapy was associated with a five-fold increase in fatal intracranial haernorrhages (odds ratio 5.02, 95% confidence interval 1.56 to 16.18). There was a non-significant trend towards more early deaths or clinically significant intracranial haemorrhages in higher dose group. No difference in late deaths or extra-cranial haemorrhages was shown between low and higher doses. However, very few of these events occurred. No difference was shown between the different thrombolytic agents tested. Conclusions There is not enough evidence to conclude whether lower doses of thrombolytic agents might be safer or more effective than higher doses in acute ischaemic stroke. It is not possible to conclude whether one agent might be better than another, or which route of administration might be best.
【摘要】 目的 探讨急性脑梗死溶栓治疗的疗效及安全性。 方法 2004年1月-2009年5月58例急性脑梗死患者，按接受尿激酶治疗时已发病时间分为3组，均接受尿激酶150万U加生理盐水150 mL静脉滴注溶栓治疗。分别在治疗后0、1、3、9 h进行神经功能评价，1、3、7 d进行神经功能评价及复查头颅CT。 结果 发病3 h内与发病3~6 h内溶栓治疗效差异无统计学意义（Pgt;0.05）；发病3 h内、3~6 h内与发病6~9 h尿激酶溶栓治疗疗效差异均有统计学意义（Plt;0.05）；发病6~9 h尿激酶溶栓治疗疗效差，多例并发脑出血，安全性差。 结论 发病6 h内的脑梗死患者，只要无禁忌证均应尽快行尿激酶溶栓治疗；发病6 h后的脑梗死患者，不宜尿激酶溶栓治疗；伴房颤者的溶栓治疗因样本量过小研究无意义，有待进一步研究。【Abstract】 Objective To discuss the efficacy and safety of thrombolytic therapy for acute cerebral infarction. Methods A total of 58 patients with acute cerebral infarction from January 2004 to May 2009 were enrolled in this study. Based on the onset time before accepting urokinase treatment, the patients were divided into three groups. All of them accepted thrombolytic treatment with 1.5 million U of urokinase and 150 ml of saline solution intravenously. Neurological function evaluation was carried out 0, 1, 3, and 9 hours after the treatment. Another neurological function evaluation and skull CT were done 1, 3, and 7 days later, respectively. Results There was no statistical difference between the efficacy of the treatment within 3 hours and between the 3rd hour and the 6th hour after the onset of the disease. However, there was a significant difference between the efficacy within 3 hours and between the 6th and 9th hour, and between the efficacy from the 3rd hour and 6th hour and from the 6th hour and the 9th hour after the onset of the disease. Between the 6th and the 9th hour after the onset, the efficacy and safety were poor with many cases of combined cerebral bleeding. Conclusions For patients within 6 hours after the onset of cerebral infarction, as long as no contraindications exists, thrombolytic therapy should be carried out as soon as possible; 6 hours after the onset, patients should not be treated with thrombolytic therapy. Further study is needed for patients combined with atrial fibrillation due to the small sample size in this study.
Objective To explore the effect of renal microcirculation following severity acute pancreatitis （SAP） on renal injury and to explore the protection effect of urokinase on them. Methods A total of 192 Wistar rats were randomized divided into normal control group， SAP group， and urokinase group， then rats of 3 groups were sub-divided into 2， 6， 12， and 24 hours group， each group enrolled 16 rats. Of the 16 rats in each subgroup， 8 rats underwent blood flow of renal test， other 8 rats were sacrificed to get blood samples and to perform histopathological examination. The rat models of SAP were established by retrograde injecting with 5% sodium taurocholate into the cholangiopancreatic duct. Radioactive biomicrosphere technique was used to measure the blood flow of renal， levels of plasma thromboxane B2（TXB2） and 6-keto-prostaglandin F1α （6-Keto-PGF1α） were tested by the TXB2 kit and 6-Keto-PGF1α kit， and histopa-thological changes of renal tissues were observed by using HE staining. Results Compared with normal control group at the same time point， the blood flow of renal were lower （P＜0.05）， activity ratio of TXB2 to 6-Keto-PGF1α were higher（P＜0.01）， and the histopathological injury were worse （P＜0.01） in rats of SAP group and urokinase group. Compared with SAP group， the blood flow of renal at 2， 6， and 12 hours in urokinase group were higher （P＜0.01）， the activity ratios of TXB2 to 6-Keto-PGF1α were lower （P＜0.01）， and the histopathological injury were lighter （P＜0.05） in all the 4 time points of urokinase group. Conclusions The renal microcirculation dysfunction and increase of activity ratio of TXB2 to 6-Keto-PGF1α may play an important role in renal injury following SAP in early stage. Urokinase can protect the renal from such injuries.
Objective To evaluate the efficacy of intrapleural urokinase treatment for unloculated tuberculous pleural effusion. Methods Chinese Conference Data, Chinese Biomedical Database, VIP Database,Wanfang Database, Cochrane Library, PubMed, and Evidence-based Medical Evaluation Database were searched up to February 2012, and the studies as references of eligible articles were also searched. Randomized controlled trials were included for evaluating the efficacy of intrapleural urokinase treatment for unloculated tuberculous pleural effusion. Mean difference MD and 95% confidence interval ( 95% CI) were calculated for the efficacy of urokinase in the treatment. After the test for heterogeneity, forest map was used to analyze the efficacy of intrapleural urokinase treatment. The funnel plot was used to discuss the publication bias. Results Nine randomized controlled trials met all eligible criteria. This meta-analysis indicated that compared with the conventional treatment, the urokinase treatment increased total drainage( pumping liquid) ( P lt; 0. 000 01) , decreasd residual pleural thickening ( P lt; 0. 000 01) , improved lung function with significant increase in FEV1% pred ( P lt; 0. 000 01) . Conclusions Compared with the conventional treatment( anti-tubercular treatment in combination with pumping pleural effusion) , the treatment which injects urokinase to chest cavity can increase total pleural effusion, decrease residual pleural thickening, and improve the lung function.
ObjectiveTo investigate the therapeutic effects of thrombolysis infusion via microcatheter on the treatment of central retinal artery occlusion(CRAO). MethodsUrokinase (UK) was directly infused via ophthalmic artery (OA) by microcatheter (6 patients) or via intravenous (7 patients) to dissolve the thrombus. The patency of the artery was evaluated by fundus fluorescein angiography (FFA), and the effect of fibrinolytic activity on the systemic changes was observed by blood biochemical examination simultaneously. ResultsIn 6 patients in the microcatheter group, 5 had completely and 1 had partly reopened OA on the morrow of UK infusion with the patency rate of 83.33%, while in 7 patients in vein group, 3 completely reopened, 2 partly reopened and 2 obstructed OA were found with the patency rate of 42.86%. The difference between the two groups was significant. No obvious change of index of blood coagulation system was found in catheter group, which had great disparity compared with the vein group.ConclusionUrokinase infusion via microcatheter in CRAO has better therapeutic impact and smaller effect on systemic action. (Chin J Ocul Fundus Dis, 2005,21:16-19)
Objective To investigate the therapeutic effects of throm bolytic drug infusion via carotid artery on experimental central retinal artery occlusion (CRAO), and observe the changes of fibrinolytic activity in the system ic circulation. Methods To dissolve the thrombi in 15 cats (30 eyes) with CRAO established by laser irradiating a branch of central retinal a rtery after intravenous injection of photochemical drugs, urokinase (UK) was dir ectly infused via carotid artery in 5 cats (10 eyes) in group A or intravenously injected in 5 cats (10 eyes) in group B, and isotonic saline solution was intra venously injected in 5 cats (10 eyes) in group C respectively. The patency of the artery was evaluated by fundus fluorescein angiography. Moreover, the changes of fibrinolitic activity in the blood were observed by blood biochemical examination. Results Four hours after UK infusion, the complete repatency proportion was 80% (5 cats 8 eyes) in group A, and 50% (4 cats 5 eyes) in group B. There was significant difference between the two groups. Besides, after the infusion, the indexes of coagulation, fibrinolysis, and anti-fibrinolysis in group A were better than those in group B and C (Plt;0.01). Conclusion In the treatment of experimental CRAO, thrombolytic drug infusion via carotid artery is better and more effective than via intravenous injection, which may provide a new method of thrombolytic drug delivery and animal models. (Chin J Ocul Fundus Dis，2004，20：186-188)
Urokinase plasminogen activator receptor (uPAR) is a membrane protein which is attached to the cellular external membrane. The uPAR expression can be observed both in tumor cells and in tumor-associated stromal cells. Thus, in the present study, the human amino-terminal fragment (hATF), as a targeting element to uPAR, is used to conjugate to the surface of superparamagnetic iron nanoparticle (SPIO). Flowcytometry was used to examine the uPAR expression in different tumor cell lines. The specificity of hATF-SPIO was verified by Prussian blue stain and cell phantom test. The imaging properties of hATF-SPIO were confirmed in vivo magnetic resonance imaging (MRI) of uPAR-elevated colon tumor. Finally, the distribution of hATF-SPIO in tumor tissue was confirmed by pathological staining. Results showed that the three cells in which we screened, presented different expression characteristics, i.e., Hela cells strongly expressed uPAR, HT29 cells moderately expressed uPAR, but Lovo cells didn't express uPAR. In vitro, after incubating with Hela cells, hATF-SPIO could specifically combined to and be subsequently internalized by uPAR positive cells, which could be observed via Prussian blue staining. Meanwhile T2WI signal intensity of Hela cells, after incubation with targeted probe, significantly decreased, and otherwise no obvious changes in Lovo cells both by Prussian blue staining and MRI scans. In vivo, hATF-SPIO could be systematically delivered to HT29 xenograft and accumulated in the tumor tissue which was confirmed by Prussian Blue stain compared to Lovo xenografts. Twenty-four hours after injection of targeting probe, the signal intensity of HT29 xenografts was lower than Lovo ones which was statistically significant. This targeting nanoparticles enabled not only in vitro specifically combining to uPAR positive cells but also in vivo imaging of uPAR moderately elevated colon cancer lesions.