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。     

Correlation of hand bone mineral density with the metacarpal cortical index and carpo:metacarpal ratio in patients with rheumatoid arthritis

This study proposed an assessment of the correlation of hand bone mineral density measured by dual energy x-ray absorbtiometry (DXA) with the carpo:metacarpal (C:MC) ratio and metacarpal cortical index (CI) in patients with rheumatoid arthritis (RA). The correlation of total hand BMD, CI and C:MC ratio with BMD at other sites, the Health Assessment Questionnaire (HAQ) and Larsen scores were also examined. The hand and axial BMD of 30 female patients were also compared with 29 age-matched healthy female controls. Total hand BMD values of patients were significantly lower than the control group. There was no significant difference between groups in axial measurements. CI correlated moderately with the second metacap (II.MC) midshaft and total hand BMD. The C:MC ratio correlated with II.MC midshaft and total hand BMD. Total hand BMD correlated moderately with the AP spine (L2-L4) and femoral neck BMD. Larsen scores showed weak negative correlation with II.MC midshaft BMD and CI. Grip strength correlated weakly only with total hand BMD. The results indicated that CI may reflect cortical bone mass of the hand accurately and did not predict bone density of the spine or hip in patients with RA. The C:MC ratio is a useful method for evaluating progression of wrist involvement and may be related to the loss of hand bone mineral density associated with disease process.     

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。     

肺靶向米托蒽醌明胶微球的研究

采用二步法制备米托蒽醌明胶微球,球径范围为5.1～25.0μm的占总数87.36%,体外释药与原药相比t1/2延长4倍,DTA曲线上的特征吸热峰为133℃,经37℃,RH75%考察3月,几乎无变化。经小鼠体内分布试验表明具有明显的肺靶向性,靶向效率增加3～35倍,肺中药代动力学行为可用一室开放模型描述,平均滞留时间延长10h。     

Long-term oral ciprofloxacin in the treatment of prosthetic valve endocarditis due to Pseudomonas aeruginosa.

Prosthetic valve endocarditis caused by Pseudomonas aeruginosa is refractory to medical treatment alone and early valve replacement is necessary. We describe a 40-year-old patient in whom endocarditis developed in the early postoperative period, and reoperation was not considered feasible. Ciprofloxacin was administered orally in order to suppress bacteremia for 36 months. Long-term oral ciprofloxacin may provide an opportunity in the treatment of prosthetic valve endocarditis caused by Ps. aeruginosa in patients who are unfavorable candidates for reoperation.