Relationships among tumor burden, tumor size, and the changing concentrations of fibrin degradation products and fibrinolytic factors in the pleural effusions of rabbits with VX2 lung tumors

The VX2 tumor is derived from a papilloma virus-induced rabbit epithelial cell line. If VX2 tumor cells (trapped in a plasma clot) are introduced intravenously into NZW rabbits, the cells lodge in the lung capillary bed and produce tumors. Independently of the tumor burden (ie, the total tumor weight per rabbit), approximately 15% of rabbits with VX2 lung tumors accumulate an effusion in the interpleural space and this pleural effusion contains products of hemostasis. We hypothesized that these products were of intra-tumoral origin and that they changed in concentration as tumor burden increased. Interrelationships among lung-, tumor-weights, and pleural effusion volumes, and the concentrations of fibrinolytic factors, their catabolic products, and other proteins of pleural effusions were measured in rabbits with a wide range of tumor burdens. Positive correlations between tumor burden and total lung weight and between pleural effusion volume and net lung weight suggested that interstitial fluid from the stroma of tumors passed directly into the extravascular space of the lung(s) and into the interpleural space(s). Analyses of pleural effusions indicated that plasminogen-, alpha(2)-antiplasmin-, and plasminogen activator inhibitor-1-related proteins, urokinase-like- and tissue-plasminogen activator activities, and vascular endothelial growth factor increased in concentration up to a tumor burden of approximately 20-25 g. Plasmin activity and intact fibrinogen were absent. The concentration of fibrin(ogen) degradation products did not change significantly up to a tumor burden of approximately 25 g but increased substantially as tumor burdens exceeded 25 g. In conclusion, interstitial fluid from tumors enters the extravascular space of the host and may accumulate with fluid from non-tumor sources as a pleural effusion. The concentrations of fibrinolytic factors and their products in pleural effusions reflect the tumor burden of the rabbit. Conceivably, the components of a malignant effusion contain much information about the extent of tumor growth.     

纤溶酶相关蛋白在冠心病患者中的表达

目的:了解冠心病患者是否存在组织型纤溶酶原激活物(t-PA)及纤溶酶原激活抑制物Ⅰ(PAI-Ⅰ)功能紊乱,以及这两个指标与血脂、胰岛素抵抗的相关关系。方法:选择2004年1月至2006年1月于我院住院就诊的冠心病患者作为观察对象。按临床类型分为SAP组、UAP组、AMI组、OMI组,并设健康对照组。检测t-PA、PAI-Ⅰ、胰岛素敏感性指数(IAI)、胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL)等指标。结果:(1)健康对照组t-PA高于各型冠心病组(P<0.05),AMI组t-PA低于其余各型冠心病组(P<0.05);健康对照组PAI-Ⅰ低于各型冠心病组(P<0.05),AMI组PAI-Ⅰ高于其余各型冠心病(P<0.05)。(2)t-PA与IAI呈正相关,与TC、TG、LDL呈负相关;PAI-Ⅰ则与IAI呈负相关,与TC、TG、LDL呈正相关。(3)各病例组t-PA于治疗后有所升高,PAI-Ⅰ于治疗后有所下降(P<0.05)。结论:冠心病患者存在明显的纤溶功能紊乱,且以急性期为重,并且纤溶功能紊乱与胰岛素抵抗、血脂异常等因素有关。     

纤溶和凝血功能变化与2型糖尿病微血管病变的关系

目的探讨凝血与纤溶功能变化在糖尿病微血管病变中的临床意义。方法纤溶酶原激活物抑制物-1（PAI-1）活性采用发色底物法，纤维蛋白原（Fg）采用免疫浊度法测定。结果糖尿病无微血管病变组血浆PAI-1和Fg水平高于小常对照组（P〈0．05），糖尿病微血管病变组血浆PAI-1和Fg水平明显高于无微血管病变组及正常对照组（P〈0．01）。结论2型糖尿病患者存在血液的高凝及低纤溶状态，在发生2型糖尿病微血管病变后更为明显，检测2型糖尿病患者血浆中PAI-1和Fg水平，对糖尿病微血管病变的预防和治疗具有一定的临床意义。     

在放射性肾损伤纤维性修复中的分子病理机制

目的为探讨纤溶酶原激活物抑制因子-1(PAI-1)在放射性肾损伤纤维性修复中的作用和意义,揭示其发病的分子病理机制。方法24只雄性健康的Wistar大鼠以30Gy60Coγ线单次双肾局部照射,于照射后4个不同时相点活杀,取肾组织进行常规病理学观察及原位分子杂交,观察PAI-1mRNA表达的变化。结果纤维化的肾组织PAI-1表达较正常对照组增高,与纤维化程度呈正相关。结论PAI-1可能在肾放射性损伤后纤维性修复的发生及发展中起重要的作用。     

Antibodies to tissue-type plasminogen activator (t-PA) in patients with inflammatory bowel disease: high prevalence, interactions with functional domains of t-PA and possible implications in thrombosis

BACKGROUND: Patients with inflammatory bowel disease (IBD) have an increased prevalence of thromboembolic events. The pathogenetic mechanisms of these events include reduced fibrinolysis, which may be caused by antibodies to tissue-type plasminogen activator (t-PA). OBJECTIVES: To evaluate anti-t-PA antibodies in patients with IBD, considering clinical, biochemical and functional characteristics. PATIENTS AND METHODS: We immunoenzymatically measured anti-t-PA antibodies in plasma from 97 consecutive IBD patients and 97 age- and sex-matched healthy controls. We also assessed the antibody interactions with different epitopes of t-PA, the antibody inhibition on t-PA activity and the correlations with clinical features and other serum antibodies. RESULTS: IBD patients had higher median anti-t-PA antibody levels (5.4 U mL(-1) vs. 4.0 U mL(-1); P < 0.0001): 18 patients were above the 95th percentile of the controls (OR 5.3; 95% CI 1.7-16.3; P < 0.003), and the six with a history of thrombosis tended to have high levels (6.9 U mL(-1)). Anti-t-PA antibody levels did not correlate with IBD type, activity, location or treatment, or with age, sex, acute-phase reactants or other antibodies. The anti-t-PA antibodies were frequently IgG1 and bound t-PA in fluid phase; they recognized the catalytic domain in 10 patients and the kringle-2 domain in six. The IgG fraction from the three patients with the highest anti-t-PA levels slightly reduced t-PA activity in vitro. CONCLUSIONS: The prevalence of anti-t-PA antibodies is high in IBD patients. By binding the catalytic or kringle-2 domains of t-PA, these antibodies could lead to hypofibrinolysis and contribute to the prothrombotic state of IBD.     

诊断超声介导微泡造影剂助溶兔静脉血栓的体内实验研究

目的 研究诊断超声结合自制白蛋白微泡造影剂在体内的溶栓效应,并探讨其与尿激酶联用在溶栓方面的协同作用及溶栓机制.方法 32只健康家兔建立股静脉血栓模型,分为单纯尿激酶组、超声+微泡造影剂组、超声+微泡造影剂+尿激酶组和阳性对照组.根据前期的体外实验所确定的最佳参数组合,并联合尿激酶进行溶栓,利用彩色多普勒超声技术对各组不同时间点15 min、30 min、60 min的血管再通情况进行检测,评价血管的再通率.取溶栓治疗后的兔股静脉标本进行免疫组化检测,比较各组管腔内部结构及溶栓效果,并对其溶栓机制进行探讨.结果 治疗15 min与30 min后,超声+微泡造影剂+尿激酶组的血管再通率较单纯尿激酶组、超声+微泡造影剂组均显著增加,差异有统计学意义(P<0.05);治疗60 min后,超声+微泡造影剂+尿激酶组管再通评分要明显优于其他两组.免疫组化检测结果示超声+微泡造影剂+尿激酶组治疗60 min后股静脉内血栓结构崩解,纤维素断裂,血管腔大部分融通,优于治疗15 min、30 min时的溶栓效果.结论 诊断超声结合自制微泡造影剂在体内具有明显的溶栓效应,与尿激酶联用在溶栓方面有很好的协同作用.     

超早期脑梗死溶栓治疗联合应用依达拉奉后神经功能缺损症状的临床观察

目的观察超早期脑梗死溶栓治疗联合应用新型自由基清除剂依达拉奉的神经功能缺损症状情况。方法选择69例入我院的超早期脑梗死患者,随机分为重组组织型纤溶酶原激活剂（rt-PA）溶栓联合自由基清除剂依达拉奉治疗组（35例）和单独使用rt-PA溶栓治疗组（34例）,比较治疗15 d、30 d和90 d时的美国国立卫生院卒中量表评分（NIHSS）。结果联合溶栓组治疗后15 d时NIHSS评分0-1分28.6%（10/35）与单纯溶栓组17.6%（6/34）比较有统计学意义（P〈0.05）;30 d时分别为34.3%（12/35）和23.5%（8/34）,比较有显著性意义（P〈0.05）;90 d时分别为42.9%（15/35）和23.5%（8/34）,比较有也显著性意义（P〈0.05）。两组15 d、30 d和90 d的疗效差异有统计学意义。结论超早期脑梗死溶栓治疗联合应用新型自由基清除剂依达拉奉的能够更有效地改善病人的神经功能缺损症状。     

NK026680 inhibits T-cell function in an IL-2-dependent manner and prolongs cardiac allograft survival in rats

NK026680 is a triazolopyrimidine derivative that has been shown to inhibit dendritic cell maturation and activation. Here, we examined the immunosuppressive properties of NK026680 on T-cell function and assessed its immunosuppressive efficacy in an ACI (RT1^av1 haplotype) to Lewis (RT1^l) rat heart transplantation model. The effects of NK026680 on T-cell proliferation, activation, and cytokine production were investigated in vitro. Heart transplant recipient rats were administered NK026680 daily for 14 days post-transplantation. In addition to graft survival time, alloimmune responses and graft histology at 4-10 days post-transplantation were assessed. NK026680 was found to inhibit proliferation, CD25 upregulation, IL-2 production, and cell cycle progression in αCD3/αCD28-stimulated murine T cells. These effects were likely due to suppression of the p38 mitogen-activated protein kinase pathway and the subsequent inhibition of p65, c-Fos, and to a lesser extent, c-Jun. Daily NK026680 treatment suppressed alloimmune responses, prevented cellular infiltration into allografts, and prolonged graft survival. The anti-rejection effects of NK026680 were enhanced by tacrolimus. In conclusion, NK026680 inhibits the activation of T cells and prolongs cardiac allograft survival in rats. These features make it a potential candidate immunosuppressant for the treatment of organ transplant patients in the future.     

腹腔镜结直肠癌手术对腹膜微结构损伤和纤维溶解分子表达的影响

目的探讨腹腔镜结直肠癌根治术对腹膜微结构损伤和腹膜纤维溶解分子表达的影响。方法前瞻性纳入2011年6月至2012年2月问山西省人民医院收治的50例结直肠癌患者．根据患者意愿和医生决策分为腹腔镜组（27例）和开腹组（23例）。分别在光镜和电镜下观察术后腹膜微结构损伤程度：采用ELISA法比较手术前后腹膜组织型纤溶酶原激活物t-PA和纤溶酶原激活物抑制因子1（PAI-1）水平的改变。结果术后标本光镜和电镜观察显示,开腹组肠管浆膜完整性受损、系膜脂肪细胞与间皮细胞覆盖脱失、炎性细胞聚集程度较腹腔镜组严重,两组损伤评分比较的总平均秩次分别为38．22和14．67,差异有统计学意义（P〈0．01）。术后网膜组织t-PA、肠管浆膜组织t-PA及PAI-1水平的差异均无统计学意义（均P〉0．05）;但腹腔镜组网膜组织中PAI-1水平显著低于开腹组（P〈0．05）。结论相对于开腹手术,腹腔镜结直肠癌根治术腹膜损伤程度较轻,对腹膜纤溶功能的影响较小．有利于防止肠粘连的形成。