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。     

吗啡对大鼠肝脏缺血再灌注损伤的影响

目的:缺血再灌注是肝脏手术和肝移植术中不可避免的病理过程,吗啡对于心肌缺血再灌注损伤以及对抗心肌细胞凋亡等方面已有了很大的研究进展.观察吗啡对大鼠肝缺血再灌注损伤的影响,并分析其可能作用途径.方法:实验于2006-08/2007-03在辽宁医学院附属医院外科实验室完成,动物实验方法符合动物伦理学要求.①实验分组及方法:选用Wistar大鼠60只,按随机数字表法分成4组(n=15),正常对照组、假手术组、缺血再灌注组及缺血再灌注 吗啡干预组,缺血再灌注组建立大鼠肝脏缺血再灌注损伤模型;缺血再灌注 吗啡组于缺血再灌注前给予0.3 mg/kg盐酸吗啡注射液腹腔内注射.②实验评估:于再灌注90 min后,各组大鼠经左心室取血,测定血浆中谷丙转氨酶、谷草转氨酶活性;取肝脏组织,应用流式细胞仪检测肝细胞凋亡率,应用免疫组化法检测半胱氨酸蛋白酶3的表达变化.结果:60只大鼠均进入结果分析.①血浆谷丙转氨酶、谷草转氨酶活性:缺血再灌注组显著高于正常对照组和假手术组(P＜0.01),吗啡 缺血再灌注组显著低于缺血再灌注组(P＜0.01).②肝细胞凋亡率:缺血再灌注组显著高于正常对照组和假手术组(P＜0.01),吗啡 缺血再灌注组显著低于缺血再灌注组(P＜0.01).③肝脏组织半胱氨酸蛋白酶3的表达:缺血再灌注组显著高于正常对照组和假手术组(P＜0.01),吗啡 缺血再灌注组显著低于缺血再灌注组(P＜0.01).结论:吗啡可抑制缺血再灌注损伤后肝细胞的凋亡,减轻肝脏的损伤,从而起到保护肝脏的作用.     

Antipyretic,anti-inflammatory and analgesic activity of <Emphasis Type="Italic">Acacia hydaspica</Emphasis> R. Parker and its phytochemical analysis

Background

Inflammation and pain underlies several pathological conditions. Synthetic drugs used for the management of these conditions carry severe toxic effects. Globally efforts are ongoing to introduce novel medicinal plants to develop effective, economic and innocuous drugs. The current study was aimed at investigating the antipyretic, anti-inflammatory and analgesic activity of methanol extract of A. hydaspica aerial parts (AHM) and its active fraction. Furthermore identification and isolation of polyphenolic compounds was carried out to identify the active principles.

Methods

Yeast induced pyrexia, Paw edema, acetic acid-induced writhing and hot plate test were carried out in vivo. HPLC-DAD analysis and combination of different chromatographic techniques, involving vacuum liquid chromatography (VLC) and flash chromatography (FC) were carried out for chemical characterization. The structural heterogeneity of flavanols was characterized by ESI- MS, ¹H NMR, ¹³C NMR and ²D NMR spectroscopic analyses, and also by comparison with reported literature.

Results

Oral administration of A. hydaspica methanol extract (AHM) and A. hydaspica ethyl acetate fraction (AHE), showed dose and time dependent decrease in body temperature in yeast induced pyrexia, comparable to standard, Paracetamol. AHM and AHE (150 mg/kg) significantly (p?<?0.001) inhibit pain sensation in various pain models, i.e. acetic acid induced writhing and hot plate test. Similarly AHM and AHE demonstrated an anti-inflammatory effect in carrageenan-induced paw edema in rats and 150 mg/kg dose being distinctly more effective (91.92% inhibition). When studied on prostaglandin E₂ (PGE₂) induced edema in rats, AHM and AHE showed maximum inhibition of edema at 150 mg/kg after 4 h. HPLC chromatogram of AHM revealed the presence of gallic acid, catechin, rutin and caffeic acid. Chromatographic separation and structure characterization of AHE, has led to the identification of three flavan-3-ol derivative including 7-O-galloyl catechin, +catechin and methyl gallate, which have been reported for the first time in A. hydaspica.

Conclusion

These results revealed that the presence of bioactive compounds in A. hydaspica might be responsible for the pharmacological activities, confirming the indigenous utility of A. hydaspica against inflammatory disorders.

     

Drug Use, Increasing Incarceration Rates, and Prison-Associated HIV Risks in Thailand

Background: Incarceration is a known risk for HIV infection in Thai drug users. Through the 1990s, incarceration rates for drug-related offenses rose sharply, whereas HIV prevention and drug treatment in prisons remained limited. Methods: We assessed HIV and incarceration risks for injection drug users (IDU) and non-IDU in a large treatment center cohort in northern Thailand to investigate HIV and prison risks in this period. We used Thai Bureau of Corrections data to assess incarceration and prevention funds in prisons, 1992–2000. Results: Among 1,865 drug user in the treatment cohort, 503 (27.0%) had ever been jailed. Men (OR 3.3, 95% CI 2.1, 5.2), IDU (OR 6.3, 95% CI 5.1, 7.9), and men who have sex with men (MSM) (OR 3.4, 95% CI 1.8, 6.3) were more likely to have been jailed. Among male IDU who had ever been jailed (N = 272), 15.8% had used drugs in prison. In a multivariate model, incarceration and ever IDU remained independently associated with HIV infection; IDU, MSM behaviors, and harmful traditional practices remained independently associated with having been jailed. From 1992 to 2000, overall alleged narcotics offenses increased from 117,000 to 276,000/year. The number of persons incarcerated for narcotics offenses increased fivefold from 1992 to 1999, from 12,860 to 67,440. For FY 2000, narcotics treatment accounted for 0.06% of the Thai corrections budget, whereas HIV programs in prisons were 0.017%. Conclusions: Incarceration rates for narcotics offenses have increased sharply in Thailand, whereas prevention has lagged. Having been jailed is an important independent risk for HIV infection among Thai male drug users, especially IDU and MSM. HIV prevention and drug treatment are urgently needed in Thai prisons.