羧烷基化合成萘普生工艺改进

１－溴－２－甲氧基萘与０－对在苯磺酰乳酸乙酯（１）在无水氯化铝催化下化Ｆｒｉｅｄｅｌ－Ｃｒａｆｔｓ反应，还原脱溴直接合成ｄｌ－１ａ萘普生（３），以上反应均在“一锅”内完成，收率达９５。     

FDA：长效β受体激动剂需限制使用

适当使用时,LABAs利大于弊,可继续用于治疗哮喘。FDA建议仅用于哮喘控制药物如吸入性皮质激素不能有效缓解病情的患者。     

Aetiological factors for oral manifestations of HIV

OBJECTIVES: Describe the oral diseases in HIV-infected individuals in London, UK and identify social and medical factors related to the presence of specific oral diseases.
DESIGN: Cross-sectional analytic study.
SETTING: Dental clinics.
SUBJECTS: Consecutive sample of 456 patients with HIV infection.
METHODS: Social and medical history and clinical examinations. Univariate and logistic regression analysis.
OUTCOMES: Presence of HIV-associated oral disease.
RESULTS: 80% of patients with AIDS and 50% of patients with HIV had a specific oral disease. The most common diseases were hairy leukoplakia (30%), erythematous candidiasis (24%), pseudomembranous candidiasis (14%), angular chielitis (6%), necrotising periodontal disease (8%) and non-recurrent ulceration (6%).
CONCLUSIONS: The presence of erythematous candidiasis was not related to advanced HIV disease. Pseudomembranous candidiasis, hairy leukoplakia and mucosal ulceration were significantly associated with advanced HIV disease. Smoking was also identified as a strong aetiological factor in oral diseases. Longitudinal studies are required to further explore the prognostic significance of oral diseases in HIV infection.     

Prostate Tumor Growth Can Be Modulated by Dietarily Targeting the 15-Lipoxygenase-1 and Cyclooxygenase-2 Enzymes

The main objectives of our study were to determine the bioavailability of omega-3 (ω-3) to the tumor, to understand its mechanisms, and to determine the feasibility of targeting the ω-6 polyunsaturated fatty acids (PUFAs) metabolizing 15-lipoxygenase-1 (15-LO-1) and cyclooxygenase-2 (COX-2) pathways. Nude mice injected subcutaneously with LAPC-4 prostate cancer cells were randomly divided into three different isocaloric (and same percent [%] of total fat) diet groups: high ω-6 linoleic acid (LA), high ω-3 stearidonic acid (SDA) PUFAs, and normal (control) diets. Tumor growth and apoptosis were examined as end points after administration of short-term (5 weeks) ω-3 and ω-6 fatty acid diets. Tumor tissue membranes were examined for growth, lipids, enzyme activities, apoptosis, and proliferation. Tumors from the LA diet-fed mice exhibited the most rapid growth compared with tumors from the control and SDA diet-fed mice. Moreover, a diet switch from LA to SDA caused a dramatic decrease in the growth of tumors in 5 weeks, whereas tumors grew more aggressively when mice were switched from an SDA to an LA diet. Evaluating tumor proliferation (Ki-67) and apoptosis (caspase-3) in mice fed the LA and SDA diets suggested increased percentage proliferation index from the ω-6 diet-fed mice compared with the tumors from the ω-3 SDA-fed mice. Further, increased apoptosis was observed in tumors from ω-3 SDA diet-fed mice versus tumors from ω-6 diet-fed mice. Levels of membrane phospholipids of red blood cells reflected dietary changes and correlated with the levels observed in tumors. Linoleic or arachidonic acid and metabolites (eicosanoid/prostaglandins) were analyzed for 15-LO-1 and COX-2 activities by high-performance liquid chromatography. We also examined the percent unsaturated or saturated fatty acids in the total phospholipids, PUFA ω-6/ω-3 ratios, and other major enzymes (elongase, Delta [Δ]-5-desaturase, and Δ-6-desaturase) of ω-6 catabolic pathways from the tumors. We observed a 2.7-fold increase in the ω-6/ω-3 ratio in tumors from LA diet-fed mice and a 4.2-fold decrease in the ratio in tumors from the SDA diet-fed mice. There was an increased Δ-6-desaturase and Δ-9 desaturase enzyme activities and reduced estimated Δ-5-desaturase activity in tumors from mice fed the SDA diet. Opposite effects were observed in tumors from mice fed the LA diet. Together, these observations provide mechanistic roles of ω-3 fatty acids in slowing prostate cancer growth by altering ω-6/ω-3 ratios through diet and by promoting apoptosis and inhibiting proliferation in tumors by directly competing with ω-6 fatty acids for 15-LO-1 and COX-2 activities.     

3,5-甾二烯化合物的合成及抗早孕活性

以18-甲基-17β-羟基-17α-乙炔基-雌甾-4-烯-3-酮(18-甲基炔诺酮),17β-羟基-17α-乙缺基-雌甾-4-烯-3-酮(炔诺酮),17β-羟基-17α-乙炔基-雄甾-4-烯-3-酮(妊娠素)和17a-羟基孕甾-4-烯-3,20二酮(17α-羟基黄体酮)为原料,经NaBH,还原、脱水、双键转位和酯化等反应合成一系列3,5-甾二烯化合物,用¹HNMR和MS证明了它们的结构。动物筛选结果表明,17β-丙酰氧基-17α-乙炔基-雌甾-3,5-二烯(IV_b2有明显的抗早孕活性。中断早期妊娠的作用似与其雌激素活性有关。