AdCMVCD／5FC自镣基因系统治疗CABG术后再狭窄

目的 研究胞嘧啶脱氨酶基因/5—氟胞嘧啶自杀基因系统对冠状动脉旁路移植术后再狭窄的治疗作用。 方法将含AdCMVCD的病毒上清加压注入兔颈外静脉管腔,半小时后剪下该静脉并用Cuff技术移植于兔颈动脉上,以单纯移植组和AdCMVLacz为对照,通过光镜和电镜观察平滑肌细胞的形态变化,并对血管桥外径、管腔、内膜、中膜面积和外弹力膜周长及管腔相对丧失率进行定量分析,以观察抑制内膜和中膜增生、防止血管再狭窄的效果。 结果 治疗组的内膜和中膜面积明显小于两个对照组;管腔丧失率亦明显减少,AdCMVCD组为3.68±0.42％,单纯移植组为9.68±0.41％.P<0.01。结论 AdCMVCD自杀基因系统对冠状动脉旁路移植术后再狭窄有明显的治疗作用。     

3-氯-2,4,5-三氟苯甲酸的合成

目的：合成3-氯-2，4，5-三氟苯甲酸。方法：以3，4，5，6--四氟苯二甲酸为起始原料，经酯化、氨化、重氮化和桑德德迈耳反应制得3--氯苯甲酸。结果：酯化时使用发烟硫酸；重氮化和桑德德迈耳反应时溶剂由水改为水和二氯乙烷，使产率增加，质量提高。结论：该合成路线条件温和，操作简单，收率提高到61．8％。     

火把花根片对哮喘豚鼠抗炎机制及其对肺泡灌洗液IL-5受体mRNA表达的影响

目的　探讨火把花根片对哮喘豚鼠抗炎作用机制及其对肺泡灌洗液 (BALF)白介素 5(IL 5)受体mRNA表达的影响。方法　 3 2只健康豚鼠随机分为 4组 :正常对照组 ,哮喘组 ,地塞米松治疗组 ,火把花根片治疗组。后 3组制作成哮喘豚鼠模型 ,再激发用药。测定肺泡灌洗液的细胞总数和细胞分类 ,观察肺组织的病理改变 ,进行BALF的IL 5受体mRNART PCR半定量分析。结果　火把花根片治疗组BALF的嗜酸性粒细胞 (Eos)数较正常组和哮喘组 ,差异均有显著性 ,分别为P <0 0 5和P <0 0 1。肺组织病理切片 ,火把花根片组充血水肿明显 ,但Eos肺组织浸润较哮喘组有明显减少。BALF的IL 5受体mRNART PCR半定量分析显示 ,火把花根片治疗组与地塞米松治疗组差异无显著性 ,P >0 0 5,但和正常组与哮喘组比较差异有显著性 ,P <0 0 1。结论　火把花根片能抑制哮喘豚鼠的气道炎症 ,为临床治疗哮喘提供初步的理论基础     

肠易激综合征治疗药物的评价

目的 :评价肠易激综合征药物治疗的疗效、不良反应和药物经济学 ,以供临床用药参考。方法 :通过查阅近期国内、外相关文献总结、分析。结果与结论 :目前肠易激综合征尚无确切的治疗方法 ,主要是对症治疗和综合治疗 ,包括患者教育、心理疗法、饮食调整等 ,而药物治疗主要在于改善胃肠道动力 ,解除肠管痉挛 ,减轻肠管扩张以及抗菌消炎等 ,并且尽可能实施个体化治疗方案     

Effects of in utero exposure to finasteride on androgen-dependent reproductive development in the male rat.

Finasteride is a specific inhibitor of type II 5alpha-reductase, the enzyme that converts testosterone (T) to the more potent androgen receptor agonist dihydrotestosterone (DHT). In utero exposure to androgen receptor antagonists and T biosynthesis inhibitors have induced permanent effects on androgen-sensitive end points such as anogenital distance (AGD), nipple retention, and malformations of the male rat reproductive tract. The objectives of this study were to (1) characterize the dose response of finasteride-mediated alterations in androgen-dependent developmental end points, (2) determine whether prenatal exposure to finasteride permanently decreases AGD or results in nipple retention, and (3) evaluate whether AGD or nipple retention is predictive of adverse alterations in the male reproductive tract. Pregnant Crl:CD(SD)BR rats (n=5-6/group) were gavaged with either vehicle or finasteride at 0.01, 0.1, 1.0, 10, or 100 mg/kg/day on gestation days 12 to 21. All male offspring were monitored individually until necropsy on postnatal day (PND) 90. The present study design has been used previously for other antiandrogens and is sensitive to perturbations of the male rat reproductive tract. Decreases in AGD on PND 1 and increases in areolae-nipple retention on PND 13 were significantly different from controls in all finasteride-exposed male rats. Finasteride-induced changes in AGD and nipple retention were permanent in male rats exposed to finasteride at and above 0.1 mg/kg/day. On PND 90, dorsolateral and ventral prostate lobes were absent in 21 to 24% of rats exposed to 100 mg/kg/day finasteride and weighed significantly less at and above 10 mg/kg/day. In the highest dose group, 73% of animals had ectopic testes, much higher than previously reported. The most sensitive malformation other than decreased AGD and nipple retention was the dose-dependent increase in hypospadias. The lowest observed adverse effect level (LOAEL) for finasteride-induced permanent effects in this study was 0.1 mg/kg/day based on permanent changes in AGD and nipple retention. Finasteride-induced changes in AGD and retention of nipples were highly predictive of hypospadias, ectopic testes, and prostate malformations even though some animals with retained nipples or decreased AGD may not have had other reproductive tract malformations. In summary, prenatal exposure to finasteride specifically inhibited DHT-mediated development with little to no change in T-mediated development.     

TMB-8抑制5-HT和KCl引起大鼠脑血流量减少

目的研究TMB-8对5-HT和KCl引起的大鼠脑血流量(CBF)减少的作用。方法用激光多普勒血流仪测量大鼠CBF,在人工脑脊液灌流液中加入TMB-8和工具药进行干预。结果12.5, 25和50 μmol·L^-1 TMB-8对大鼠CBF无明显影响,TMB-8可抑制5-HT引起的大鼠CBF减少。在1 μmol·L^-1 5-HT引起大鼠CBF持续下降的状态下,TMB-8可浓度依赖的增加大鼠CBF。TMB-8也可抑制KCl引起的大鼠CBF减少。在20 mmol·L^-1 KCl引起大鼠CBF持续下降的状态下,TMB-8可浓度依赖的增加大鼠CBF。结论TMB-8可抑制5-HT和KCl引起的大鼠CBF减少,也可浓度依赖的增加被5-HT和KCl所减少的大鼠CBF,改善大鼠缺血区脑血供。     

腺苷A1受体阻断剂对学习记忆的影响及机制分析腺苷A1受体阻断剂对学习记忆的影响及机制分析

目的探讨腺苷A₁受体阻断剂对学习记忆的影响及其与胆碱能、氨基酸能神经的关系。方法采用避暗实验、分光光度法和HPLC法,观察腺苷A₁受体特异性阻断剂8-环戊-1,3-二丙基黄嘌呤(DPCPX)对东莨菪碱(Scop)、2-氨基-5-磷戊酸(AP₅)致小鼠记忆障碍及脑胆碱酯酶(AChE)活性、氨基酸水平的影响。结果DPCPX可显著改善Scop致记忆障碍,但对AP₅致记忆障碍无影响；在体内外高剂量DPCPX可显著抑制小鼠脑AChE活性；DPCPX icv可显著升高小鼠脑Glu和Asp含量,降低GABA含量,使脑内Glu/GABA比值显著升高。结论腺苷A₁受体特异性阻断剂DPCPX可显著改善Scop而不能改善AP₅致记忆障碍,在高剂量时可影响脑AChE活性和脑氨基酸水平、升高脑内Glu/GABA比值。     

5-甲基-7,4’-二羟基异黄酮水溶性衍生物的合成及其抗缺氧活性

目的5-甲基-7,4’-二羟基异黄酮水溶性衍生物的合成及其抗缺氧活性的比较。方法三氟化硼-乙醚催化的“一锅法”工艺制备母体化合物1,并通过甲基化和磺化反应合成衍生物2～4,常压耐缺氧试验评价其活性。结果化合物3和4水溶性强,且抗缺氧作用等价于母体化合物。结论新合成的水溶性化合物3和4具有明显的抗缺氧活性。     

Cellular uptake and concentrations of tamoxifen upon administration in poly(ε-caprolactone) nanoparticles

Purpose: In an attempt to increase the local concentration of tamoxifen in estrogen receptor positive breast cancer cells, we have prepared and characterized poly (ε-caprolactone) (PCL) nanoparticle formulation. Methods: PCL (mol wt 14,800 daltons) nanoparticles were prepared by the solvent displacement method in acetonewater system in the presence of Pluronic F-68. PCL nanoparticles, labeled with rhodamine 123, were incubated with MCF-7 estrogen receptor positive breast cancer cells to determine uptake, intracellular distribution, and localization as a function of time. Intracellular drug concentrations over a specified period of time using different initial doses were examined using tritiated [³H]-tamoxifen. Results: A significant fraction of the administered rhodamine 123-loaded PCL nanoparticles was found in the perinuclear region of the MCF-7 cells, where estrogen receptors are also localized, after 1 hour of incubation. Measurements of the intracellular concentrations revealed that most of the administered nanoparticle dose was internalized within the first 30 minutes of incubation, and the uptake followed saturable transport kinetics. Conclusion: Results of this study show that PCL nanoparticles were rapidly internalized in MCF-7 cells and intracellular tamoxifen concentrations followed a saturable process. This approach may provide better therapeutic benefit by delivering the drug locally, near the tumor cells, for a longer period of time.     

Synthesis of [14C]ABT‐770, matrix metalloproteinase inhibitor (MMPI), labelled in the phenoxy ring

The MMPI [¹⁴C]ABT‐770 (1) , N‐[(1S)‐1‐[(4,4‐Dimethyl‐2,5‐dioxo‐1‐imi‐dazolidinyl)methyl]]‐2‐[[4′‐(trifluoromethoxy)[1,1′‐biphenyl]‐4‐yl]oxy]ethyl]‐N‐hydroxyformamide was synthesized in 8 steps using 4‐bromophenol‐UL‐¹⁴C (10) as a starting material. The Carbon‐14 label was introduced in one of the metabolically stable biphenyl rings. The key sequence of the synthesis was a three‐step one‐pot reaction in which the hydantoin moiety was introduced, the imine oxidized and further hydrolyzed to get the penultimate precursor to [¹⁴C]ABT‐770 (1) in 56% yield. Copyright © 2003 John Wiley & Sons, Ltd.