Alzheimer’s disease: the impact of age-related changes in reproductive hormones

Recent findings from the Womens Health Initiative (WHI) have raised considerable concern over prolonged use of opposed and unopposed oral conjugated equine estrogen (CEE), given the increased risk of serious adverse effects, including stroke and venous thromboembolic complications. Furthermore, results from the WHI Memory Study (WHIMS) indicated that over 5 years of therapy with Prempro impaired performance on global cognitive tests and nearly doubled the risk of dementia. These surprising findings were contradictory to cumulative evidence from basic science, epidemiological and some intervention studies suggesting hormone therapy was cardioprotective and could potentially reduce the risk of dementia. This review paper focuses on the neurobiology of estrogen, summarizing the clinical evidence for neuroprotective and cognition-enhancing efficacy of estrogen. Further, the paper briefly discusses variables that may account for the unexpected findings of WHIMS, and offers suggestions for future research.     

"9·11"事件对于世界与中国经济的影响

美国的经济在持续了10年的增长后开始下滑,"9·11"事件使美国经济由软着陆变为硬着陆,加剧了经济的衰退,殃及全球.受低迷的世界经济形势以及加入WTO影响,中国国际收支将从顺差走向逆差,有赖外资流入弥补.中国必须加速调整策略,加强经济安全,从多方面启动内需以促进增长.     

Pheromone components of the female elephant hawk-moth,Deilephila elpenor,and the silver-striped hawk-moth,Hippotion celerio

By means of gas chromatographic and mass spectroscopic methods, and combined GC-electroantennogram and electrosensillogram techniques, (E)-11-hexadecenal and (10E, 12E)-10,12-hexadecadienal [(E,E)-bombykal is also the main constituent of the pheromone of the silver-striped hawk-mothHippotion celerio. The biological activity of the substances was demonstrated with electroantennogram and single cell recording, and the physiological efficacy of the different hexadecadienal isomers compared.Pheromones, 79; as Pheromones, 78 is taken: Wu, Cai-Hong, and Bestmann, H. J., Chinese Science Bulletin34 (1989) 1475; pheromones, 77: Attygalle, A. B., Steghaus0Kovac, S., Ahmed, V. U., Maschwitz, U., Vostrowsky, Ol, and Bestmann, H. J., Naturwissen-schaften78 (1991) 90.     

Human and rodent type 1 11β-hydroxysteroid dehydrogenases are 7β-hydroxycholesterol dehydrogenases involved in oxysterol metabolism

Interconversion between cortisone and the glucocorticoid receptor ligand cortisol is carried out by 11-hydroxysteroid dehydrogenase (11-HSD)isozymes and constitutes a medically important example of pre-receptor control of steroid hormones. The enzyme 11-HSD type 1 (11-HSD1) catalyzes the conversion of cortisone to its active receptor-binding derivative cortisol, whereas 11-HSD type 2 performs the reverse reaction. Specific inhibitors against the type 1 enzyme lower intracellular levels of glucocorticoid hormone, with an important clinical application in insulin resistance and other metabolic disorders. We report here on the in vitro oxysterol-metabolizing properties of human and rodent 11-HSD1. The enzyme, either as full-length, membrane-attached, or as a transmembrane domain-deleted, soluble form, mediates exclusively conversion between 7-ketocholesterol and 7-hydroxycholesterol with similar k_cat values as observed with glucocorticoid hormones. Thus, human, rat, and mouse 11-HSD1 have dual enzyme activities like the recently described 7-hydroxysteroid dehydrogenase/11-hydroxysteroid dehydrogenase from hamster liver, but differ fundamentally from the latter in that 7-OH rather than 7-OH dehydrogenase constitutes the second activity. These results demonstrate an enzymatic origin of species differences in 7-oxysterol metabolism, establish the origin of endogenous 7-OH cholesterol in humans, and point to a possible involvement of 11-HSD1 in atherosclerosis.Received 30 December 2003; received after revision 16 February 2004; accepted 16 February 2004     

星际HⅡ/H_2O脉泽的一种激发机制

本文对于星际HⅡ/H_2O脉泽提出一种重要的激发机制——通过紫外辐射吸收的水的选择性预离解机制,并用它解释了HⅡ/H_2O脉泽能级布居反转的原因,预言了一系列水脉泽跃迁的存在,证明了它与各种天文条件的自洽.     

p53对STK11的转录调控研究

PJ综合征(Peutz-Jeghers syndrome)是一种常染色体显性遗传疾病.其致病基因所编码的蛋白质为一种丝氨酸/苏氨酸蛋白激酶(STK11).STK11可以激活AMPK,p53等多条信号通路.文中在克隆了STK11的基本启动子区域基础上,用生物信息学分析预测该区域内可能存在p53结合位点和Sp1结合位点.EMSA结果证实了信息学分析的预测.Sp1结合位点核心碱基定点突变后,其PGL3重组突变体质粒萤光素酶活性下降1.9倍;p53结合位点核心碱基的定点突变后,PGL3重组突变体质粒萤光素酶活性下降14.6倍,均有统计学意义.利用内源表达STK11的L02细胞株,瞬时转染pcDNA3.1-myc-his-B(-)-p53,经Real-time PCR和Western blotting检测发现,p53过表达可以上调STK11的表达,因此p53对STK11的表达有正反馈调节放大作用.     

具有液晶相的四烷氧基苯并菲-1,4-二醌的合成

研究合成了6,7,10,11-四戊氧基苯并菲-1,4-二醌和6,7,10,11-四庚氧基苯并菲-1,4-二醌两个新化合物,经核磁氢谱和碳谱、质谱、IR及元素分析等测定,并对其结构进行了表征.该类化合物在紫外可见光区250~630 nm的范围有光吸收.采用偏光显微镜和示差扫描量热仪对其性能进行了研究,结果表明,该材料具有液晶性.此外,本文对该类化合物的合成方法也进行了改进,利用亚硝酸钠/三氟乙酸/二氯甲烷体系替代了常用的硝酸铈铵/四氢呋喃/水体系,反应时间从原来的2 h缩短至15 min,并在室温下完成;在合成中间体1,2-二甲氧基-6,7,10,11-四烷氧基苯并菲时,采用二氯甲烷作为溶剂,将三氯化铁与3,3′,4,4′-四烷氧基联苯的摩尔比从8∶1提高到10∶1,反应时间从原来的5 h缩短至2 h.