石杉碱甲类似物的研究II.N-甲基吡啶酮石杉碱甲类似物的合成

石杉碱甲(1)是从中草药石杉属植物千层塔(Lycopodium serratum Thunb.)中分得的一种高效可逆的乙酰胆碱酯酶抑制剂,临床试验证实它对早老性痴呆症有显著疗效。本文报道N-甲基吡啶酮石杉碱甲类似物2和3的合成。2-甲氧基-5-甲氧羰基-11-亚甲基-5,9-甲撑环辛-7-烯并吡啶(9)在乙腈中用三甲基氯硅烷和碘化钠选择性脱保护以定量的产率得吡啶酮10,再用甲醇钠和碘甲烷甲基化得N-甲基吡啶酮11,11经碱性水解,Curtius重排和氨基的脱保护得N-甲基吡啶酮石杉碱甲类似物2。通过类似的途径从中间体2-甲氧基-5-甲氧羰基-7-甲基-11-酮-5,9-甲撑环辛-7-烯并吡啶(14)合成了类似物3。类似物2和3的乙酰胆碱酯酶抑制活性均低于天然石杉碱甲。     

哇巴因与地高辛对大鼠心肌钠泵α亚单位基因表达影响的对比研究

目的　对比研究哇巴因与地高辛对大鼠心肌钠泵 (Na ,K ATP酶 )亚单位基因表达的影响 ,探讨内源性哇巴因(EO)的生物学效应以及洋地黄类药物药理作用的分子机制。方法　每天给予大鼠注射小剂量哇巴因 (2 0 μg·kg 1·d 1)与地高辛 (32 μg·kg 1·d 1) ,每周测量一次大鼠血压 ;6周后处死动物 ,应用RT PCR技术在mRNA水平探讨大鼠心肌钠泵α1、α2 及α3亚单位基因表达的改变。结果　给予大鼠注射哇巴因 6周后血压明显升高 (132 6± 9 0mmHgvs 115 7± 8 2mmHg ,P <0 0 1) ,而地高辛组大鼠血压与对照组比较无明显差异。哇巴因与地高辛均可导致大鼠心肌钠泵α亚单位基因表达的改变 :两者均可引起钠泵α3亚单位表达增强 ,而对α2 亚单位表达无影响 ;哇巴因组大鼠心肌钠泵α1亚单位表达减弱 ,而地高辛组α1亚单位表达无改变。结论　哇巴因与地高辛可导致不同的钠泵基因表达改变 ,这可能是内源性哇巴因发挥生理作用的分子机制之一 ,并且可能是哇巴因与地高辛药理及毒理作用 (包括两者对血压的调节 )不同的重要原因。     

Risk of Mental Illness in Offspring of Parents With Schizophrenia,Bipolar Disorder,and Major Depressive Disorder: A Meta-Analysis of Family High-Risk Studies

Objective: Offspring of parents with severe mental illness (SMI; schizophrenia, bipolar disorder, major depressive disorder) are at an increased risk of developing mental illness. We aimed to quantify the risk of mental disorders in offspring and determine whether increased risk extends beyond the disorder present in the parent. Method: Meta-analyses of absolute and relative rates of mental disorders in offspring of parents with schizophrenia, bipolar disorder, or depression in family high-risk studies published by December 2012. Results: We included 33 studies with 3863 offspring of parents with SMI and 3158 control offspring. Offspring of parents with SMI had a 32% probability of developing SMI (95% CI: 24%–42%) by adulthood (age >20). This risk was more than twice that of control offspring (risk ratio [RR] 2.52; 95% CI 2.08–3.06, P < .001). High-risk offspring had a significantly increased rate of the disorder present in the parent (RR = 3.59; 95% CI: 2.57–5.02, P < .001) and of other types of SMI (RR = 1.92; 95% CI: 1.48–2.49, P < .001). The risk of mood disorders was significantly increased among offspring of parents with schizophrenia (RR = 1.62; 95% CI: 1.02–2.58; P = .042). The risk of schizophrenia was significantly increased in offspring of parents with bipolar disorder (RR = 6.42; 95% CI: 2.20–18.78, P < .001) but not among offspring of parents with depression (RR = 1.71; 95% CI: 0.19–15.16, P = .631). Conclusions: Offspring of parents with SMI are at increased risk for a range of psychiatric disorders and one third of them may develop a SMI by early adulthood.Key words: schizophrenia, bipolar disorder, depression, offspring, meta-analysis     

胰腺癌组织VEGF和MVD表达与CT灌注成像的关系

血管内皮生长因子作为肿瘤血管生成的一种主要调控因子,与微血管密度密切相关．胰腺癌组织的血管内皮生长因子和微血管密度的测定对于判断患者的预后,指导临床治疗和判断疗效等具有重要作用．CT灌注成像可以通过无创伤检查反映胰腺癌的肿瘤血管构成, 在治疗前后提供有价值依据,对胰腺癌的诊治有重要意义．