大剂量萘哌地尔在家犬体内的药物动力学

目的 :建立HPLC测定家犬血浆中萘哌地尔浓度的方法 ,研究大剂量萘哌地尔胶囊在家犬体内的药物动力学。方法 :健康家犬 5只 ,单剂量给予萘哌地尔胶囊 2 0 0mg后 ,在不同时间点从后肢静脉取血 ,血浆样品碱化后经乙醚提取 ,以乙腈 :磷酸盐缓冲液 (pH 6 .5 ) (6 0 :40 )为流动相 ,由ODSC18分析柱分离测定 ,紫外 2 30nm为检测波长 ,维拉帕米为内标。血药浓度数据用 3p97药物动力学程度处理。结果 :线性范围为 10～ 12 0 0ng·ml-1;方法回收率为98 83%～ 10 1 5 0 % ;日间RSD≤ 5 5 6 % ,日内RSD≤ 3 30 %。单剂量给予家犬萘哌地尔胶囊 2 0 0mg后 ,血药浓度随时间变化规律符合一室开放模型 ,T1/2Ke为 1 91～ 4 99h ,Tmax为 1 87～ 3 2 1h ,Cmax为 338 79～ 414 0 4ng·ml-1。结论 :本方法简便、回收率高、重现性好 ,用于大剂量萘哌地尔在动物体内的药物动力学研究 ,切实可行。     

Mechanism of Graft Damage Caused by NTPDase1-activated Macrophages in Acute Antibody-Mediated Rejection

ObjectivesTo investigate the effect and mechanism of macrophage activation and graft damage caused by nucleoside triphosphate diphosphohydrolase 1 (NTPDase1) in acute antibody-mediated rejection (AMR).MethodsAcute AMR was induced in different skin-grafted nude mouse models with wild-type NTPDase1 expression, transgene-enhanced NTPDase1 expression, or NTPDase1 gene knockout. Several methods (eg, real-time fluorescence quantitative polymerase chain reaction, high-performance liquid chromatography [HPLC], immunofluorescence, flow cytometry, and luciferin/luciferase assays) were used to study (at the histologic and molecular levels) the extracellular adenosine diphosphate (ADP) concentration, macrophage proliferation, major histocompatibility complex (MHC) class II antigen expression on the surface of macrophages, B-cell activating factor (BAFF) expression in the peripheral blood serum, and the total number of SmIg-positive B cells during acute AMR. The relative activity of NTPDase1 in B cells and epithelial cells, pathologic changes, and the incidence of positive C4d deposition around the capillaries of skin grafts on the different nude mice were studied.ResultsMacrophages proliferated significantly when acute AMR occurred. The higher the NTPDase1 expression level, the lower the extracellular ADP concentration, the expression of MHC class II antigens on the surface of macrophages, the expression of BAFF in the peripheral blood serum, and the total number of SmIg-positive B cells, indicating negative correlations. The relative activity of NTPDase1 in B cells and epithelial cells of the skin graft was different among the different mice. The higher the NTPDase1 expression level, the lower the degree of pathologic damage to the skin graft.ConclusionsImbalance in extracellular ADP degradation by NTPDase1 may promote macrophage activation, and activated macrophages may be an important cause of graft damage.     

Clinicopathological characteristics,prognosis, and chemosensitivity in patients with metastatic upper tract urothelial carcinoma

PurposeTo investigate the clinical characteristics, chemosensitivity, and outcome of metastatic upper tract urothelial carcinoma (UTUC).Patients and MethodsRecords of patients with metastatic UTUC since January 2005 were retrieved from a database that included clinical and survival data. Statistical analyses including survival and multivariate analyses of factors were respectively performed by the Kaplan-Meier method and Cox proportional hazard model.ResultsA total of 250 consecutive UTUC cases were evaluated. There were 56 patients (22.4%) with initially diagnosed stage IV disease. The most common metastatic sites were lung (39.6%), distant lymph nodes (39.2%), bone (19.6%), liver (18.0%), and adrenal gland (7.2%), respectively, and the local recurrence rate was 10.4%. Two hundred thirteen patients received first-line chemotherapy. The overall response rate was only 28.7% and the median progression-free survival time was only 5.0 months. The overall survival time of the cohort was 18.0 months. Multivariate analyses showed that initially diagnosed stage IV disease, number of metastatic organs ≥3, no response to chemotherapy and cycles of chemotherapy ≤2 were adverse prognosticators for overall survival.ConclusionUTUC presented to be more prone to metastasize than locally recur and thought to have low chemosensitivity. Stage IV disease at initial diagnosis, number of metastatic organs, response and cycles of chemotherapy were independent prognosticators for metastatic UTUC.     

Migration of Alkaline Constituents and Restoration Evaluation in Bauxite Residue Disposal Areas

Bulletin of Environmental Contamination and Toxicology - Bauxite residue is a highly alkaline waste from alumina refining, and is mainly disposed by stacking with high environmental risks....     

复方延胡索颗粒的制备、质控与初步戒毒作用的研究

目的：研究复方延胡索颗粒的制备、质量控制方法、观察该制剂对吗啡依赖鼠的治疗作用。方法：选用黄芪、延胡索、甘草、远志、酸枣仁、石菖蒲、芸香等七种中药组方制备复方延胡索颗粒,以有效部位部性物碱及有效成分四氢帕马丁的含量作为制备方法的筛选指标及复方延胡索颗粒制的质控指标。总生物碱的含量用非水电位滴定法测定,四氢帕马丁的含量以单波长反射锯齿式薄层扫描外标两点法测定,以该中药制剂治疗吗啡依赖性大鼠自然戒断模型体质量变化百分率作为初步戒毒作用的观察指标。结果：四氢帕马丁在1－6μg范围内线性关系良好（r=0.9992)其仪器精密度、同板精密度良好（RSD＜3．0％）,且在显色后0．5－6h内结果稳定,制剂的加样回收率约为975,复方延胡索颗粒中剂量组（0．6g/kg)和高剂量组（1．2g/kg)对吗啡依赖鼠的体质量下降可产生显治疗作用（P＜0．05,P＜0．01）。结论：本制剂一定剂量可有效控制吗啡身体依赖性大鼠戒断后的体质量下降,对吸毒可能有促进康复的作用。     

交锁髓内钉治疗胫骨不稳定性骨折

目的 探讨交锁髓内钉治疗胫骨不稳定骨折的效果。方法 本研究38例中不扩髓法31例,扩髓法7例;闭合穿针33例,开放穿针5例;静力性固定32例,动力性固定6例。结果 平均随访时间10月（3～22月）采用Johner-Wruh评分标准,对治疗的最终结果证定：优31例,良5例,中1例,差1例。骨折平均愈合时间;闭合性骨折16周（11～24周）,开放性骨折18周（12～26周）,2例延迟愈合（闭合性骨折、开放性骨折各1例）。无感染及骨不连。结论 文锁髓内钉是治疗胫骨不稳定骨折的较好方法之一。