胸腔闭式引流联合尿激酶注入对包裹性胸腔积液的临床研究

目的:探讨胸腔闭式引流联合尿激酶注入对包裹性胸腔积液的临床疗效。方法:对我院2007年2月-2011年4月收治的包裹性胸腔积液患者87例,随机分为实验组以及对照组,实验组采用胸腔闭式引流联合尿激酶注入进行治疗,对照组采用常规治疗。结果:实验组患者临床疗效明显优于对照组(P<0.05);实验组患者治疗后其积液中蛋白量以及白细胞含量明显低于对照组(P<0.05);实验组患者治疗时间、胸膜壁厚度等比较明显优于对照组(P<0.05)。结论:对包裹性胸腔积液患者采用胸腔闭式引流联合尿激酶注入进行治疗,可有效改善患者预后,提高患者临床治疗效果。     

尤瑞克林联合尿激酶超早期治疗改善脑梗死患者预后

目的：观察尤瑞克林联合尿激酶超早期治疗对改善脑梗死患者预后的疗效,探讨其临床适用性。方法：选择从2009年3月至2012年8月于我院住院治疗的48例超早期急性脑梗死患者,随机分为实验组25例和对照组23例,对照组患者使用尿激酶进行溶栓治疗,实验组在此基础上加用尤瑞克林联合治疗。观察两组患者治疗后神经功能的恢复情况,治疗有效率及预后稳定性情况。结果：两组患者治疗后NIHSS评分均较治疗前改善（P〈0．05）;与对照组比较,实验组治疗后NIHSS较治疗前下降更多（P〈0．05）;实验组治疗有效率高于对照组（X2=-4．69,P〈0．05）;实验组患者服药后的治疗安全性与对照组的相当,差异无明显统计学意义（X2=0．33,P〉0．05）。结论：尤瑞克林联合尿激酶超早期治疗较单用尿激酶疗效好,安全性好。     

尿激酶介入动脉溶栓治疗26例急性脑梗死临床分析

目的:观察缺血性脑梗死急性期尿激酶介入动脉溶栓治疗的临床疗效。方法:应用尿激酶早期动脉内溶栓治疗急性脑梗死26例。溶栓前及溶栓后2 h、30 d进行神经功能缺损评分,同时观察并发症及疗效。结果:颈内动脉闭塞9例,大脑中动脉主干(M1)段闭塞6例,大脑前动脉闭塞4例,椎基底动脉系统闭塞3例。溶栓治疗后10例获得完全再通,9例部分再通,3例未开通。临床症状完全恢复及明显好转16例,占总病例61.5%。术后NIHSS评分较术前明显提高。并发颅内出血1例。再通后发生再闭塞1例。结论:尿激酶动脉溶栓治疗急性脑梗死安全、有效、可行,但其远期疗效还需进一步观察。     

尿激酶静脉溶栓治疗急性心肌梗死的疗效观察--附35例报告

目的 观察尿激酶静脉溶栓治疗急性心肌梗死的疗效.方法将66例急性心肌梗塞住院患者随机分成两组,溶栓组35例在常规治疗的同时,用尿激酶静脉溶栓治疗,非溶栓组仅用常规治疗,两组进行比较分析.结果 溶栓组血管再通率74.3%,非溶栓组为25.81%,两组间有明显差异(P<0.05),住院4周的病死率,溶栓组为2.86%,非溶栓组为16.16%,两组间有显著差异(P<0.01).结论 尿激酶静脉溶栓能明显提高急性心肌梗死患者的血管再通率和抢救成功率,降低近期病死率.     

Inactivation of human high- and low-molecular-weight urokinases. Analysis of their active site

We previously demonstrated that 3,4-dihydro-3,4-dibromo-6-bromomethylcoumarin (dihydrocoumarin I) inhibited high-molecular-weight urokinase through a mechanism-based (suicide) inactivation (M. Reboud-Ravaux, G. Desvages and F. Chapeville (1982) FEBS Lett. 140, 58-62). In order to define the site of alkylation, peptic peptides were prepared from urokinase (heavy form) treated first by tritiated dihydrocoumarin I. After separation by reverse-phase HPLC, the labelled fragments were sequenced. His-46 in the B-chain of urokinase (heavy form) had been selectively alkylated, proving that this amino acid forms part of the active site. 3,4-Dihydro-3-benzyl-6-chloromethylcoumarin (dihydrocoumarin II) was more reactive than dihydrocoumarin I against urokinase (heavy form) by a factor of 130. Low-molecular-weight urokinase was inactivated by dihydrocoumarin II slightly more slowly than urokinase (heavy form), showing a decrease of 30% in the corresponding second-order rate constant. In contrast, dihydrocoumarin I displayed an analogous reactivity against light and heavy forms of urokinase. As expected, in the absence of the alkylating moiety, such as in 3,4-dihydro-3-benzylcoumarin (dihydrocoumarin III), no inactivation was observed. It is note-worthy that dihydrocoumarin II which carried an extra-aromatic group fitted well within the active site of light and heavy urokinases, suggesting a nonpolar character for their primary binding site.     

老年颈内动脉系统急性脑梗死动脉溶栓的疗效观察

目的:探讨老年颈内动脉系统急性脑梗死动脉溶栓的疗效。方法:对我院老年科收治的63例老年颈内动脉系统急性脑梗死随机分为股动脉组以及颈动脉组,其中股动脉组患者30例,对其采用经皮股动脉穿刺微导管介入尿激酶溶栓治疗,颈动脉组患者33例,对其采用经皮患侧颈动脉穿刺尿激酶溶栓治疗。结果:对两组患者治疗前、术后2h以及术后30d采用NIHSS评分比较,两组患者NIHSS评分在术后2h及术后30d均较术前有明显改善(P<0.05);对两组患者治疗相关情况比较,股动脉组患者术后2h血管再通率明显高于颈动脉组(P<0.05),两组颅内出血率未显示出统计学差异性;对两组患者术后30d牛津残障OHS评分、BI指数比较,股动脉组患者明显优于颈动脉组(P<0.05)。结论:对老年急性脑梗死患者采用经皮股动脉穿刺微导管介入或采用经皮患侧颈动脉穿刺尿激酶溶栓治疗,均可有效改善患者预后,提高患者的临床疗效,两组相比较,股动脉组更能显示出优良的治疗率。     

Oral urokinase: absorption, mechanisms of fibrinolytic enhancement and clinical effect on cerebral thrombosis

The oral administration of the thrombolytic agent urokinase was studied. Its intestinal absorption was demonstrated in dogs by the observation of a prolonged urokinase activity in plasma with a concomitant lytic effect on artificial thrombi after intraduodenal administration. In situ intestine-liver perfusion experiments in dogs revealed that a plasminogen activator, distinct from the administered urokinase--thus presumed to be a tissue plasminogen activator--was liberated into the circulation in association with intestinal absorption of urokinase. Its absorption in men was demonstrated in a cross-over double blind study of oral urokinase on healthy subjects. On the basis of these results a double blind clinical trial of oral urokinase was performed on 101 patients with cerebral thrombosis. The results showed the usefulness of urokinase treatment, particularly in the early phase after the onset of stroke. The clinical effect was influenced by the plasma plasminogen level.     

CT-guided stereotactic aspiration of intracerebral hematoma--result of a hematoma-lysis method using urokinase

CT-guided stereotactic aspiration was performed in the CT room on 97 patients with hypertensive intracerebral hematomas, using a standard ventricular cannula. Residual hematomas were liquefied by urokinase and aspirated through the drainage tube. Major and minor rebleeding were seen in 7 cases. Two out of the 4 major rebleeding cases were followed by craniotomy, while the other cases were treated conservatively. More than 80% of the hematomas were aspirated in 68 cases, 50-70% in 19 cases and 30-40% in 6 cases. Operation in the CT room and hematoma lysis with urokinase is very useful for the aspiration of intracerebral hematomas.     

Linkage of extracellular plasminogen activator to the fibroblast cytoskeleton: colocalization of cell surface urokinase with vinculin

Several cell types display binding sites for [125I]urokinase (Vassalli, J.-D., D. Baccino, D. Belin. 1985. J. Cell Biol. 100:86-92) which in certain cases are occupied with endogenous urokinase. These sites appear to focus urokinase at cell surfaces and hence may participate in tissue matrix destruction and cell invasion. Recently Pollanen et al. (1987) demonstrated that the cell surface urokinase of human fibroblasts and fibrosarcoma cells is deposited underneath the cells in strands, apparently at sites of cell-to-substratum contact. Here, using immunofluorescence double labeling, we show that the urokinase strands present on human foreskin fibroblasts are colocalized with strands of vinculin, an intracellular actin-binding protein that is deposited at cell-to-substratum focal adhesion sites. Thus, this indicates linkage of the plasminogen/plasmin system both to sites of cell adhesion and to the cytoskeleton. The urokinase strands on HT 1080 fibrosarcoma cells are more numerous and have shapes that are more tortuous than those on normal fibroblasts. In intact HT 1080 cells, colocalized vinculin strands are obscured by an intense background of soluble vinculin but are apparent on isolated ventral plasma membranes. Certain properties of the urokinase strands suggest that they are related to the [125I]urokinase-binding sites that have been described by several groups: (a) incubating fibroblasts with dexamethasone for 48 h or at pH 3 at 5 degrees C for 10 min greatly decreases the number and intensity of the urokinase strands; (b) strands reappear when glucocorticoid- treated cells are incubated with exogenous 54-kD (but not 35-kD) urokinase, and this process is inhibited by a previously described 16- amino acid peptide that blocks [125I]urokinase binding to the cells.     

Urokinase binds to a plasminogen activator inhibitor type-2-like molecule in placental microvillous membranes

Placental microvillous membranes exhibited saturable binding of urokinase-type plasminogen activator with plateau achieved by 30 min at 4 degrees C and 10 min at 37 degrees C. The binding was essentially irreversible. The capacity was about 8 pmol urokinase per mg membrane protein. Half-maximal displacement of 125I-labelled urokinase was achieved with about 1.0 nM unlabelled urokinase when using 75 micrograms membrane protein/ml. 125I-labelled urokinase did not bind when treated with diisopropylfluorophosphate to block the catalytic activity. Single-chain urokinase (prourokinase), devoid of catalytic activity, did not bind. Catalytically active tissue-type plasminogen activator did compete with 125I-labelled urokinase for binding although less efficiently than urokinase. Binding activity remained in the 100,000 x g pellet after treatment of the membranes with 3 M KCl, alkaline stripping at pH 12 or extraction by the detergent Triton X-100. The binding was essentially blocked by antibodies against plasminogen activator inhibitor-type-2 (PAI-2). Sodium dodecyl sulfate polyacrylamide gel electrophoresis of solubilized membranes with bound 125I-labelled urokinase showed that the urokinase-PAI-2 complexes largely migrated in fractions corresponding to a very large Mr although no clearly defined peaks were observed. It is suggested that PAI-2 occurs in a form anchored to syncytiotrophoblast microvilli, possibly to the cytoskeleton.     

Inhibition of receptor-dependent urokinase signaling by specific Ser to Glu substitutions

We have previously reported that phosphorylation of human urokinase on Ser138/303 abolishes its catalytic-independent motogen and proadhesive abilities, whereas receptor binding is not affected. Here we show that substitution of the two relevant serines with glutamic acid residues impairs the ability of urokinase to mobilize a variety of human and mouse cell lines as well as human primary T lymphocytes. Accordingly, urokinase receptor-dependent signaling, leading to cytoskeletal rearrangements and paxillin re-distribution, does not occur in MCF-7 breast carcinoma cells exposed to 'phosphorylation-like' urokinase. Unlike the wild-type form, di-substituted urokinase is unable to induce the physical association of urokinase receptor with alphavbeta5 vitronectin receptor, which is required for MCF-7 urokinase-dependent cell migration. Finally, the di-substituted variant fails to activate p55fgr, a member of the Src tyrosine kinase family, which mediates cell migration and adhesion of U937 myelomonocytic cells. In conclusion, the finding that specific amino acid substitutions strongly interfere with the ability of urokinase to stimulate cell migration, and the associated intracellular events uncover a novel way to regulate urokinase receptor-dependent signaling.     

前列地尔联合尿激酶治疗糖尿病肾病尿蛋白的临床观察

目的:观察短期应用注前列地尔注射液、前列地尔注射液联合小剂量尿激酶对Ⅳ期糖尿病肾病患者尿蛋白的影响。方法:选取我院2005年1月～2009年12月的Ⅳ期糖尿病肾病住院患者548例,均采取强化控制血糖、血压,低蛋白饮食等基础治疗,分为前列地尔治疗组216例、前列地尔联合尿激酶治疗组332例,给予14天短期输液治疗,测定治疗前后24小时尿蛋白。结果:两组患者治疗前年龄、性别组成、糖尿病病程、血糖、血压、血脂、尿蛋白、肾功能等各项指标无显著差异。两组治疗前后各自比较,单独应用注前列地尔注射液、前列地尔注射液联合小剂量尿激酶,均可有效减少糖尿病肾病24小时尿蛋白排泄,但前列地尔注射液联合小剂量尿激酶改善尿蛋白排泄的效果较单独应用注前列地尔更显著(p<0.05),有效率更高(88.2%vs.75.4%,p<0.05);应用小剂量尿激酶未见眼底、皮肤、黏膜出血等不良反应,无凝血功能异常发生。结论:短期静脉应用前列地尔联合小剂量尿激酶治疗Ⅳ期糖尿病肾病,较单独使用前列地尔可更有效减少尿蛋白排泄,不增加眼底出血、皮肤出血、黏膜出血的风险,是一种降低糖尿病肾病尿蛋白水平的安全有效的治疗方法。     

影响尿激酶静脉溶栓治疗急性脑梗死预后因素的初步分析

目的:对影响急性缺血性脑卒中患者应用尿激酶溶栓治疗预后的相关危险因素进行初步分析及研究,为今后选择适宜应用尿激酶溶栓的患者打下基础。方法:以2015年1月1日至2015年10月31日入院且应用尿激酶静脉溶栓的38例急性缺血性脑卒中患者,根据治疗3个月后的预后情况将患者分为A组(24例,预后良好)和B组(14例,预后不良),对两组患者的预后影响因素进行分析。结果:预后良好组患者的溶栓前NIHSS评分低于预后不良组,差异具有统计学意义(P0.05)。多因素的Logistic回归分析显示,吸烟和HINSS评分与急性脑梗死尿激酶溶栓预后不良有关,差异具有统计学意义(P0.05),且NIHSS评分是预后的独立预测因素。结论:尿激酶静脉溶栓治疗脑梗死的患者,溶栓前较高的NIHSS评分可能与溶栓预后不良有关。吸烟的患者溶栓后出现预后不良的几率是不吸烟患者溶栓后预后不良的8.83倍,溶栓前NIHSS评分每增加1分,溶栓预后不良的几率增加1.76倍。     

Treatment of mouse L-cells with phorbol myristate acetate induces the secretion of a plasminogen activator inhibitor which binds to human and mouse urokinase and human tissue plasminogen activator

1. Serum-free conditioned medium from L-cells or L-cells treated with the tumor-promotor phorbol myristate acetate (PMA) was analyzed for plasminogen activator (PA) and plasminogen activator inhibitor (PAI) activity. Conditioned medium from control or PMA-treated cells did not contain detectable PA activity when assayed by SDS-PAGE and zymography. 2. Conditioned medium from PMA-treated cells, but not control cells, contained a PAI of Mr = 40,000 da when assayed by reverse zymography. 3. The L-cell PAI formed SDS-stable complexes with purified human (homo sapiens) urokinase and tissue plasminogen activator, as well as, mouse (Mus musculus) urinary PA. 4. These results indicate that biochemical and immunological differences between human and mouse urokinase and human urokinase and human tissue plasminogen activator do not influence the interaction of the L-cell PAI with these enzymes.     

Oxygen-mediated regulation of tumor cell invasiveness. Involvement of a nitric oxide signaling pathway

Tumor hypoxia is associated with a poor prognosis for patients with various cancers, often resulting in an increase in metastasis. Moreover, exposure to hypoxia increases the ability of breast carcinoma cells to invade the extracellular matrix, an important aspect of metastasis. Here, we demonstrate that the hypoxic up-regulation of invasiveness is linked to reduced nitric oxide signaling. Incubation of human breast carcinoma cells in 0.5% versus 20% oxygen increased their in vitro invasiveness and their expression of the urokinase receptor, an invasion-associated molecule. These effects of hypoxia were inhibited by nitric oxide-mimetic drugs; and in a manner similar to hypoxia, pharmacological inhibition of nitric oxide synthesis increased urokinase receptor expression. The nitric oxide signaling pathway involves activation of soluble guanylyl cyclase (sGC) and the subsequent activation of protein kinase G (PKG). Culture of tumor cells under hypoxic conditions (0.5% versus 20% oxygen) resulted in lower cGMP levels, an effect that could be prevented by incubation with glyceryl trinitrate. Inhibition of sGC activity with a selective blocker or with the heme biosynthesis inhibitor desferrioxamine increased urokinase receptor expression. These compounds also prevented the glyceryl trinitrate-mediated suppression of urokinase receptor expression in cells incubated under hypoxic conditions. In contrast, direct activation of PKG using 8-bromo-cGMP prevented the hypoxia- and desferrioxamine-induced increases in urokinase receptor expression as well as the hypoxia-mediated enhanced invasiveness. Further involvement of PKG in the regulation of invasion-associated phenotypes was established using a selective PKG inhibitor, which alone increased urokinase receptor expression. These findings reveal that an important mechanism by which hypoxia increases tumor cell invasiveness (and possibly metastasis) requires inhibition of the nitric oxide signaling pathway involving sGC and PKG activation.     

地塞米松联合尿激酶治疗结核性胸膜炎的临床效果分析

目的:探讨地塞米松联合尿激酶对结核性胸膜炎的临床效果。方法:选择2013年8月到2016年5月在我院进行诊治的结核性胸膜炎患者190例,根据随机信封抽签原则分为观察组与对照组各95例,两组都给予标准抗结核治疗方案,对照组在抗结核治疗的同时给予尿激酶治疗,观察组再给予地塞米松治疗,两组都治疗1个月。治疗后,比较两组的总有效率、不良反应的发生情况、胸腔积液完全引流时间、抽出胸腔积液总量、凝血酶原时间和凝血酶时间。结果:所有患者都注射耐受良好,未见严重并发症;观察组的总有效率(88.4%)明显高于对照组(72.6%);观察组胸腔积液完全引流时间和抽出胸腔积液总量分别为7.56±2.44d和2867.33±456.10 m L,对照组分别为9.44±2.89d和1989.92±444.20 m L,观察组胸腔积液完全引流时间明显短于对照组,且抽出胸腔积液总量显著高于对照组(P0.05)。治疗后,两组的凝血酶原时间和凝血酶时间都明显高于治疗前(P0.05),且观察组显著高于对照组(P0.05)。结论:地塞米松联合尿激酶治疗结核性胸膜炎能延长凝血酶时间和凝血酶原时间,缩短胸腔积液引流时间,增加抽出胸腔积液总量,安全性和临床疗效均较好。     

Local infusion of urokinase and heparin into renal arteries in impending renal cortical necrosis.

Two patients with presumed impending cortical necrosis, after haemolytic uraemic syndrome in one and after concealed accidental haemorrhage in the other, were treated by local infusion of urokinase and heparin into the renal artery. Both recovered and one regained normal renal function. Local infusion of anticoagulants or thrombolytic drugs into one renal artery offers the possibility of a controlled examination of the efficacy of this treatment in preventing cortical necrosis.     

Comparison of ReoPro((R)) (abciximab) versus intracoronary thrombolysis for early coronary stent thrombosis

AIMS: This study evaluated the treatment of early coronary stent thrombosis with intracoronary urokinase or the platelet glycoprotein IIb/IIIa receptor inhibitor ReoPro (abciximab). METHODS AND RESULTS: Seventy-four patients (126 stents) were treated immediately after identification of early (0-30 days) coronary stent thrombosis. Twenty-nine patients were treated with intracoronary urokinase (UK) (UK alone in 19; UK and additional balloon angioplasty in 10) and another 45 patients were given ReoPro((R)) (abciximab) (0.25 mg/kg as a bolus alone in 26, abciximab with additional balloon angioplasty in 19) within 30 days of stent implantation. TIMI grade 3 flow was obtained in 23 patients (79%) in the UK group and in 38 (84%) in the abciximab group (nonsignificant). Three patients (10%) in the UK group and one (2%) in the abciximab group underwent repeat percutaneous transluminal coronary angioplasty (PTCA) (nonsignificant). Five patients (17%) in the UK group and three (7%) in the abciximab group were referred for urgent coronary artery bypass graft surgery (CABG) because of residual thrombus and refractory ischemia (nonsignificant). Repeat revascularization was necessary in eight patients (28%) in the UK group versus four (9%) in the abciximab group (p < 0.05). Five patients (17%) in the UK group and eight (18%) in the abciximab group developed myocardial infarction (nonsignificant). Five patients (17%) in the UK group (cardiogenic shock (three), cerebral hemorrhage (one) and pneumonia (one)) and three (6.6%) in the abciximab group (cardiogenic shock (two), heart failure (one)) died within 30 days (nonsignificant). Overall, noncardiac complications (bleeding including surgical repair of groin) were observed in 11 patients (38%) in the UK group and three (7%) in the abciximab group (p < 0.001). CONCLUSION: Compared to urokinase, abciximab reduced the need for repeat revascularization procedures and the risk of noncardiac events, including bleeding complications in patients with early coronary stent thrombosis.     

动脉介入溶栓术治疗急性脑梗死的临床疗效

目的:探究动脉介入溶栓术对急性脑梗死患者的临床疗效。方法:选择我院收治的急性脑梗死患者43例并随机划分成实验组以及对照组。对照组19例予静脉内尿激酶溶栓,实验组24例予尿激酶动脉内溶栓。比较两组临床疗效、治疗前后血清脑钠肽及Hcy水平的变化。结果:实验组总有效率显著高于对照组,差异具有统计学意义(P0.05)。治疗后,两组患者血清脑钠肽、同型半胱氨酸(Hcy)水平及NIHSS评分均较治疗前降低,且与对照组比较,实验组血管总再通率较高、NIHSS评分、血清脑钠肽及Hcy水平较低,差异具备有统计学意义(P0.05)。结论:动脉介入溶栓术治疗急性脑梗死患者能够有效提高血管再通率、NIHSS评分及临床疗效,推测其与降低患者血清脑钠肽及Hcy水平相关联。     

Proliferation of a human epidermal tumor cell line stimulated by urokinase

Several tumor cells secrete significantly increased amounts of the plasminogen activator urokinase, a trypsinlike serine protease, whose biological function in tumor biology is unclear. In this study we report that cells of the human epidermal tumor cell line CCL 20.2 express about 80,000 high-affinity urokinase receptors per cell that bind active as well as diisopropylfluorophosphate-treated high-molecular-weight (HMW) urokinase. Low-molecular-weight (LMW) urokinase is not bound to the receptor. Occupation of these receptors by active HMW urokinase stimulates cell proliferation independently in the presence of plasminogen in the culture medium. LMW urokinase has again no effect on cell proliferation. Calculated on a molar basis, this effect is about 28% of that of epidermal growth factor. Active HMW urokinase might therefore provide an autocrine receptor-mediated growth-promoting mechanism for tumor cells similar to those described for other growth factors.