格列美脲与格列本脲治疗2型糖尿病疗效的系统评价

目的系统评价格列美脲与格列本脲治疗T2DM的疗效。方法计算机检索PubMed、万方等数据库从建库至2010年12月间的有关文献。按Cochrane系统评价的方法评价纳入研究的质量,使用Review Manager4．2软件进行荟萃分析。结果共纳入9个随机对照试验。结果显示：格列美脲在降低HbA1c[P=0．08,加权均数差（WMD）=-0．18,95％CI（-0．39,0．02）]、FPG[P=0．06,WM=-0．46,95％CI（-0．94,0．01）]、餐后血糖[P=O．73,WMD=-0．16,95％CI（-1．08,0．76）]、TC[P=0．22,WMD=-0．2,95％CI（-0．51,0．12）]和TG[P=0．06,WMD=-0．30,95％CI（-0．61,0．01）]方面与格列本脲无差异;在相同血糖水平下,格列美脲组FIns[P〈0．05,WMD=-0．83,95％CI（-1．21,0．45）]及餐后胰岛素[P〈0．05,WMD=-5．94,95％CI（-8．79,-3．10）]升高程度低于格列本脲组;低血糖发生率格列美脲组低于格列本脲组[P〈0．05,RR=0．66,95％CI（0．53,0．81）];在降低BMI方面格列美脲优于格列本脲[P=0．02,WMD=-1．49,95％CI（-2．7,-0．27）]。结论与格列本脲相比,格列美脲在降低血糖的同时,还能改善胰岛素抵抗及减轻体重,且低血糖发生率低,是安全有效的治疗T2DM的药物。     

吲哚美辛对β淀粉样蛋白1-42诱发BV-2细胞产生炎性介质的抑制作用

目的研究吲哚美辛对β淀粉样蛋白1-42（Aβ1-42）刺激小胶质细胞释放炎性介质一氧化氮（NO）及白细胞介素-1β（IL-1β）的抑制作用。方法应用高度纯化的BV-2小胶质细胞作为体外小胶质细胞模型，应用不同浓度吲哚美辛（10^-9，10^-8，10^-7，10^-6，10^-5mol／L）与20μmol／LAβ1—42单独或同时培养12h，测定细胞上清NO及IL，1β含量；RT—PCR法测定BV-2细胞iNOSmRNA及IL-1βmRNA的表达。结果吲哚美辛单独作用对BV-2细胞产生NO、IL-1β及iNOSmRNA、IL-1βmRNA表达无明显作用。Aβl—42可以刺激BV-2细胞产生NO及IL-1β，并增加iNOSmRNA及IL-1βmRNA表达，这种作用均可被吲哚美辛所抑制，在吲哚美辛浓度为10^-7～10^-5mol／L时抑制作用较为明显。结论在体外吲哚美辛可以降低Aβ1—42介导的BV-2细胞iNOSmRNA及IL-1βmRNA表达，从而减少NO及IL-1β的产生，上述抑制作用可能参与了吲哚美辛在阿尔茨海默病治疗中的神经元保护机制。     

The efficacy of CD3 x CD19 bispecific monoclonal antibody (BsAb) in a clonogenic assay: the effect of repeated addition of BsAb and interleukin-2

To evaluate the potency by which human T cells are targeted and activated by bispecific monoclonal antibodies (BsAbs) to lyse tumor cells, a clonogenic assay was developed. The efficacy of a CD3 x CD19 BsAb binding to both the CD3 T-cell antigen and the CD19 B-cell antigen was already proven in 51Cr-release assays and in 3-day activation cultures. To achieve more quantitative results, a 14-day clonogenic assay, based on limiting-dilution, was performed for the determination of the initial and residual number of clonogenic units obtained with a CD19+ pre-pre-B acute lymphoblastic leukemia (ALL-B) cell line. Elimination of up to 5 logs of ALL-B cells by freshly isolated peripheral blood mononuclear cells (PBMCs) cultured with BsAb plus interleukin-2 (IL-2) could be detected. The presence of human IgG did not abolish the effect. Repeated addition of each of the two agents was necessary, because a single treatment produced only a 1- to 2-log kill. CD3 monoclonal antibody and IL-2 stimulation ("lymphokine-activated killer cell" conditions) resulted in only a 2-log kill. The number of T cells proved critical in lysis of ALL-B cells, with a 5-log kill using a T-cell:B-cell ratio of 3:1 but with only a 1-log kill using a ratio of 1:1. PBMCs isolated from patients with non-Hodgkin's lymphoma, both in relapse or remission, proved to be as competent as those from healthy donors in removing ALL-B cells. This clonogenic assay shows the importance of repeated administration of CD3 x CD19 BsAb and IL-2 and offers the possibility to compare it with other therapies in B-cell malignancy.