变异催乳素受体Delta S2促使p53基因组蛋白甲基化

Background Prolactin （PRL） is a pituitary polypeptide hormone characterized by multiple biological actions includingstimulation of growth in the prostate and formation of secretory alveoli and stimulation of milk protein gene expression inthe mammary gland. PRL exerts its effect by dimerizing its receptor （PRLR） on the plasma membrane and regulating geneexpression through the JAK-Stat signal pathway. We have previously described a natural variant of the PRLR in which the$2 subdomain of the extracellular domain is missing （Delta S2）. Delta S2 PRLRs are dimerized in the absence of PRL andhave constitutive activity in the promotion of breast cancer cell growth. Enhancer of zeste homolog 2 （EZH2）, as one of thehistone-modifying enzymes, is a key factor regulating gene expression by epigenetic modification. We hypothesized thatthese constitutive activated Delta S2 PRLRs played a pathogenic role in breast cancer in part through alterations in theexpression of EZH2 and the trimethylation of histone 3 on lysine 27 （H3K27Me3）.     

survivin启动子与PSMA启动子/增强子在前列腺癌细胞系中的转录活性比较

目的:通过研究并比较前列腺特异性膜抗原(PSMA)基因启动子、增强子和survivin基因启动子在不同前列腺癌细胞系(LNCaP和PC-3细胞)中的转录活性,为前列腺癌的靶向性基因治疗提供依据。方法:采用PCR扩增PSMA基因的启动子、增强子和survivin基因启动子,分别克隆入pGL3-Basic,脂质体转染前列腺癌细胞和张氏肝细胞,检测各启动子在细胞中的转录活性。结果:survivin基因启动子在前列腺癌细胞中均具有较强活性,均明显高于PSMA启动子/增强子,其中S2pro启动活性最强,达到CMV启动子活性的1/3,然而,survivin启动子及PSMA启动子/增强子在肝细胞系中几乎不表达。结论:survivin启动子在前列腺癌细胞中具有较强启动活性,可望成为新的前列腺癌靶向性基因治疗工具。     

壳聚糖对甲硝唑凝胶体外促透作用研究

目的 考察壳聚糖(CS)对甲硝唑凝胶体外透皮速率的影响。方法 将1.0% CS作为吸收促进剂用于甲硝唑凝胶中,以泊洛沙姆p407为凝胶基质,以含2%氮酮的甲硝唑凝胶作为阳性对照,不含任何促渗剂的甲硝唑凝胶作为阴性对照,采用改良Franz扩散池进行大鼠体外皮肤渗透实验,反相高效液相色谱法（RP HPLC）法测定接受液中甲硝唑含量,计算累积透过量Q,得出Q t回归方程及稳态渗透速率J。结果 1.0%CS组和氮酮组J分别为2.841, 2.874 μg•（cm2） 1•h 1,两者差异无显著性(P＞0.05),而与阴性组相比均差异有显著性(均P＜0.05),其透皮吸收行为符合一级方程。结论 CS对甲硝唑凝胶的体外透皮吸收有较好的促进作用,值得进一步研究。     

萜烯类经皮渗透促进剂的研究与应用进展

透皮给药系统可有效避免肝脏首过效应及胃肠道降解，调控释药速率和血药浓度，降低不良反应及用药频率，提高患者顺应性。但角质层的屏障作用和药物的低渗透量，使其应用受到限制。萜烯类经皮渗透促进剂具有毒性低，促透能力强，可改善皮肤通透性，对亲水、亲脂药物均有促渗作用，低浓度高促透性的特点，在透皮给药系统中日益发挥着重要作用，显示出良好的应用前景。对其来源、分类、促透机制、实际应用、选择评价及应用前景进行综述。     

促进剂对复方脚癣灵搽剂中小檗碱和黄芩苷体外经皮吸收及其皮内滞留量的影响

目的研究复方脚癣灵的体外经皮渗透特征,确定最佳促进剂及浓度。方法以自制双室水平扩散池和离体鼠皮进行体外渗透实验,采用HPLC法同时测定盐酸小檗碱和黄芩苷的皮内含量。结果促进剂为丙二醇和薄荷醇,最佳质量分数均为3%时,复方脚癣灵中2种成分的皮内蓄积量有显著的提高。结论应用促进剂后,制剂中小檗碱与黄芩苷在离体鼠皮内有较强的蓄积作用。     

Transdermal and dermal delivery of adefovir: Effects of pH and permeation enhancers

The objective of this work was to investigate feasibility of transdermal and dermal delivery of adefovir (9-(2-phosphonomethoxyethyl)adenine), a broad-spectrum antiviral from the class of acyclic nucleoside phosphonates. Transport of 2% adefovir through and into porcine skin and effects of various solvents, pH, and permeation enhancers were studied in vitro using Franz diffusion cell. From aqueous donor samples, adefovir flux through the skin was 0.2-5.4 microg/cm2/h with greatest permeation rate at pH 7.8. The corresponding adefovir skin concentrations reached values of 120-350 microg/g of tissue. Increased solvent lipophilicity resulted in higher skin concentration but had only minor effect on adefovir flux. A significant influence of counter ions on both transdermal and dermal transport of adefovir zwitterion was observed at pH 3.4. Permeation enhancer dodecanol was ineffective, 1-dodecylazepan-2-one (Azone) and dodecyl 2-(dimethylamino)propionate (DDAIP) showed moderate activity. The highest adefovir flux (11.3+/-3.6 microg/cm2/h) and skin concentration (1549+/-416 microg/g) were achieved with 1% Transkarbam 12 (5-(dodecyloxycarbonyl)pentylammonium 5-(dodecyloxycarbonyl)pentylcarbamate) at pH 4. This study suggests that, despite its hydrophilic and ionizable nature, adefovir can be successfully delivered through the skin.     

微乳系统在透皮给药中的应用

概述了微乳透皮给药的渗透机制，微乳的各组分及结构对透皮渗透的影响和微乳中加入促渗剂的可行性。     

肉桂挥发油β-环糊精包合物制备工艺优选

目的:优选肉桂挥发油β-环糊精(β-CD)包合物制备的最佳工艺条件,并考察促渗剂对药物渗透速率的影响。方法:按L_9(3~4)正交试验表进行试验,对影响饱和溶液的3个因素进行考察,以稳态透皮速率作为评价指标,优选处方组成。以SD♂大鼠皮肤为媒介,Franz单室扩散池为体外模型,用HPLC法测定透过皮肤的药物含量。结果:最佳包合工艺条件为挥发油:β-CD=1:5(mL:g),包合温度为50℃,搅拌2h。加入促渗剂二甲基亚砜、1,2-丙二醇后的增渗倍数分别为1.38、1.65倍。结论:本包合工艺简单、方便、实用,达到了改变肉桂挥发油剂型的目的。β-CD包合物有望成为肉桂新的经皮给药系统。     

中药巴布剂的研究进展及展望

目的:解巴布剂的研究现状及其发展前景。方法:本文介绍国内巴布剂的最新研究进展,分别对现阶段巴布剂的基质原料及配比研究、透皮吸收促进剂研究、制备工艺、质量评价标准、药理毒理、临床研究进行综述。结果:巴布剂在现阶段疼痛性疾病的临床治疗中已展现出良好疗效,与其它外用制剂相比具有不可替代的优势。结论:提高其质量可控性和稳定性并将其推向规模化生产是巴布剂今后研究的主要方向,巴布剂必将有良好的市场前景。