Helical CT in the primary trauma evaluation of the cervical spine: an evidence-based approach

This review provides a summary of the cost-effectiveness, clinical utility, performance, and interpretation of screening helical cervical spine CT for trauma patients. Recent evidence supports the use of helical CT as a cost-effective method for screening the cervical spine in high-risk trauma patients. Screening cervical spine CT can be performed at the time of head CT to lower the cost of the evaluation, and when all short- and long-term costs are considered, CT may actually save money when compared with traditional radiographic screening. In addition to having higher sensitivity and specificity for cervical spine injury, CT screening also allows more rapid radiological clearance of the cervical spine than radiography. Patients who are involved in high-energy trauma, who sustain head injury, or who have neurological deficits are candidates for CT screening. Screening with CT may enhance detection of other potentially important injuries of the cervical region. Received: 17 March Revision requested: 14 April 2000 Revision received: 19 July 2000 Accepted: 19 July 2000     

一种非同位素5α-还原酶抑制剂体外筛选模型的建立和应用

目的:建立一种非同位素5α-还原酶抑制剂体外筛选模型.方法:从大鼠前列腺组织中提取物5α-还原酶,与底物睾酮(T)以及供氢体NADPH共同组成了一种微量反应体系.反应产物二氢睾酮(DHT)用酶免技术(EIA)测定,以产物生成量确定酶活性;对反应底物、NADPH、酶浓度以及反应最佳温度和时间进行了优化.结果:当底物、NADPH、酶提取物浓度分别为0.25μM、1mM和0.3mg,37℃反应60分钟可获最大酶活性.特异性5α-还原酶抑制剂非那雄胺显著降低5α-还原酶催化产物DHT的生成.进一步对24种中药进行筛选,姜黄、夏枯草等中药提取物具有5α-还原酶抑制剂作用.结论:本文建立的非同位素方法有效、可行,可作为一种体外模型筛选和研究5α-还原酶抑制剂.     

益气养阴解毒通络方对糖尿病大鼠血浆、脑组织神经肽Y和神经降压素的影响

目的探讨糖尿病并发症的发病机理及益气养阴解毒通络方对其影响。方法采用链脲佐菌素左下腹腔注射所致糖尿病大鼠模型,应用放射免疫方法,分别测定糖尿病大鼠血浆、脑组织神经肽Y(NPY)与神经降压素(NT)水平。结果糖尿病大鼠血浆NPY水平明显高于脑组织;糖尿病大鼠脑组织的NT水平明显高于血浆;糖尿病大鼠血浆和脑组织的NPY水平较正常组显著升高;糖尿病大鼠脑组织NT水平明显低于正常组;中药组大鼠血浆和脑组织的NPY和NT水平与正常组比较均无显著性差异。结论NPY与NT在糖尿病大鼠不同组织器官的分布及其作用是有差别的;影响糖尿病脑血管病变的因素可能与NPY和NT的分泌失调有关;益气养阴解毒通络方具有调节糖尿病大鼠血浆和脑组织NPY和NT水平,从而防治糖尿病性脑血管并发症的作用。     

马齿苋对2型糖尿病大鼠胰岛素抵抗的影响

目的:观察马齿苋对2型糖尿病大鼠胰岛素抵抗的影响.方法:应用小剂量链脲佐茵素加高热量饲养的方法建立实验性2型糖尿病大鼠模型,观察马齿苋对葡萄糖耐量、血清胰岛素、三酰甘油、总胆固醇、高密度脂蛋白-胆固醇、游离脂肪酸和胰岛素敏感性指数的影响.结果:马齿苋能减轻2型糖尿病大鼠体重,改善糖耐量和脂代谢紊乱,降低血清游离脂肪酸,减轻高胰岛素血症,提高胰岛素敏感性.结论:马齿苋能改善2型糖尿病大鼠之胰岛素抵抗,这可能与其改善脂代谢、降低游离脂肪酸有关.     

大明胶囊对糖尿病大鼠心肌L型Ca~(2+)通道蛋白mRNA表达的影响

目的探讨大明胶囊对2型糖尿病大鼠心肌L型Ca2+通道蛋白mRNA表达的影响。方法建立2型糖尿病大鼠模型,筛选空腹血糖值大于16.7mmol·L-1的大鼠随机分组:大明胶囊大(200mg·kg-1·d-1)、中(100mg·kg-1·d-1)、小(50mg·kg-1·d-1)剂量组、糖尿病模型组、苯乙双胍(75mg·kg-1·d-1)组,连续用药14d,用快速血糖仪测空腹血糖值。提取心肌总RNA,采用逆转录聚合酶链式反应(RTPCR)的方法,观察大明胶囊治疗后2型糖尿病大鼠心肌L型Ca2+通道蛋白mRNA水平的变化。结果2型糖尿病组大鼠心肌L型Ca2+通道蛋白mRNA表达高于正常组大鼠(P<0.01),经大明胶囊治疗后的心肌L型Ca2+通道蛋白mRNA表达降低(P<0.05),空腹血糖也明显下降。结论大明胶囊对2型糖尿病大鼠有明显的降糖作用,并且可以降低2型糖尿病大鼠心肌L型Ca2+通道蛋白mRNA的表达。     

噻唑烷二酮类药物治疗2型糖尿病的有效性及安全性

噻唑烷二酮类药物是一类新型的治疗2型糖尿病的药物,通过提高机体对胰岛素的敏感性来达到良好控制血糖的作用.噻唑烷二酮类药物还可以有效地降低2型糖尿病患者血中低密度脂蛋白胆固醇、C-反应蛋白、基质金属蛋白酶-9、纤溶酶原激活物抑制剂-11的水平等,提高高密度脂蛋白胆固醇水平,改善血管内皮功能,减少2型糖尿病患者发生心血管疾病的风险.噻唑烷二酮类药物不良反应发生率低,安全性良好.     

高内涵药物筛选方法的研究及应用

高通量药物筛选 (high throughputscreening,HTS)是 20世纪 80年代中期产生的为寻找先导物针对大量样品进行药理活性评价分析的一种技术手段,在创新药物的研究和开发中发挥了重要作用。本室于 1998年在国内率先将其用于创新药物的研究,已发现一批具有潜在研究价值的化合物 [1, 2]。近年来在药物发现领域又出现了一个新概念———高内涵药物筛选 (high contentscreening,HCS)。本文就高内涵药物筛选目前的研究和应用情况作一讨论。1　高通量药物筛选与高内涵药物筛选高通量药物筛选是以药物发现的基本规律为基础,应用药理学、生物化学…     

Novel estrogen receptor ligands and their structure–activity relationship evaluated by scintillation proximity assay for high‐throughput screening

The estrogen receptor (ER) is an important drug target with allosteric characteristics that binds orthotopic hormones and other ligands. A recently developed scintillation proximity (SPA)‐based assay for high‐throughput screening (HTS) of compound libraries was used to identify novel estrogen receptor ligands that might have ER subtype selective binding activity. Radioligand binding was determined in a multi‐detector scintillation counter designed for microtitration plates. Equilibrium binding experiments and kinetic competition tests were performed with [³H]‐estradiol and human ERα and ERβ receptors. A library of 6,000 structurally diverse compounds was screened. From this, several novel ligands were identified that showed pronounced subtype‐selective differences in ligand binding for ERα and ERβ. The observed equilibrium dissociation constant (K_d) for the binding of [³H]estradiol to ERα and ERβ receptors were approximately 0.25 and 0.64 nM, respectively. When 17β‐estradiol, raloxifene and daidzein were tested for binding affinity to ERα in a competition assay, the IC₅₀ values were 0.34, 1.31, and 75.6 nM, respectively. When tested for binding affinity to ERβ, the IC₅₀ values were 1.05, 11.4, and 10.6 nM, respectively. The results obtained show that the methodology is valid in comparison to previously published data regarding estradiol and other standard compounds (raloxifene and daidzein) binding characteristics of estrogen receptors. The assay is also well suited to applied research as a tool in HTS of compound libraries in the search of ER ligands. Several novel active compounds were identified and selected as potent ER subtype ligands. Drug Dev Res 64:203–212, 2005. © 2005 Wiley‐Liss, Inc.     

可调控的胰岛素基因表达载体的构建及其体外表达研究

目的构建四环素调控的胰岛素基因表达载体 ,并研究其体外转移后的表达情况。方法通过基因重组技术构建胰岛素基因的四环素调控表达系统 ,用脂质体转移法导入成肌细胞 ,以不同浓度的强力霉素诱导 ,检测诱导后胰岛素原mRNA表达及胰岛素 /胰岛素原水平。结果RT PCR显示此基因能在真核细胞内表达。细胞培养液中胰岛素水平在加药 2 4h后开始增加 ,至第 7天仍在增加 ,撤药后迅速下降 ,至撤药后第 5天下降到基础水平。不同诱导药物浓度诱导的胰岛素产量明显不同 (P <0 .0 5 ) ,而细胞内和培养基中的胰岛素浓度无明显差异 (P >0 .0 5 )。结论单一四环素调控的胰岛素原表达系统能在真核细胞内表达 ,并呈现强力霉素浓度依赖性     

阿卡波糖对2型糖尿病合并冠心病病人餐后代谢和内皮功能的影响

目的 :研究阿卡波糖对 2型糖尿病合并冠心病病人餐后代谢及内皮功能的影响。方法 :6 0例2型糖尿病合并冠心病病人分为 2组 ,治疗组予格列齐特和阿卡波糖口服 ;对照组予格列齐特口服 ,疗程均为 6wk。结果 :治疗后 ,2组空腹血糖、餐后 2h血糖、餐后 4h三酰甘油均明显下降 ,治疗组下降幅度较大。治疗组一氧化氮从 (76±s 31) μmol·L- 1上升至 (12 3± 6 0 ) μmol·L- 1,内皮素从 (71± 2 2 )ng·L- 1下降至 (5 4± 2 3)ng·L- 1,与对照组相比差异有非常显著意义 (P <0 .0 1) ,内皮依赖性血管舒张功能亦改善。结论 :阿卡波糖可以改善 2型糖尿病合并冠心病病人餐后代谢及内皮功能。