Hydrolysis kinetics of propylene glycol monomethyl ether acetate in rats in vivo and in rat and human tissues in vitro.

The kinetic equivalency of propylene glycol monomethyl ether (PGME), derived from propylene glycol monomethyl ether acetate (PGMEA), as well as the parent compound (PGME) following intravenous administration to Fischer 344 rats was evaluated. In addition, in vitro hydrolysis rates of PGMEA in blood and liver tissue from rats and humans were determined. The blood kinetics were determined following iv administration to rats of PGME and PGMEA of low [10 and 14.7 mg/kg body weight (bw)] or high (100 and 147 mg/kg) equimolar dosages of PGME and PGMEA, respectively. The blood time courses of PGME elimination for both dosages of both compounds were identical. Half-lives of PGMEA elimination following iv administration of 14.7 or 147 mg PGMEA/kg bw were calculated to be 1.6 and 2.3 min, respectively. Rat and human in vitro hydrolysis rates of PGMEA were determined by incubation of 5 or 50 microg PGMEA/ml in whole blood or liver homogenate. The rate of loss of PGMEA was more rapid in rat blood than in human blood, with hydrolysis half-lives of 36 and 34 min in human blood and 16 and 15 min in rat blood for the 5 and 50 microg/ml concentrations of PGMEA, respectively. In contrast the rate of loss of PGMEA in human and rat liver homogenate incubations was similar, 27-30 min and 34 min, respectively. These data demonstrate the rapid hydrolysis of PGMEA in vivo to its parent glycol ether, PGME and that, once hydrolyzed, the kinetics for PGME derived from PGMEA are identical to that for PGME. This study supports the use of the toxicological database on PGME as a surrogate for PGMEA.     

Permeant lipophilicity and vehicle composition influence accumulation of dyes in hair follicles of human skin

In skin and hair research drug targeting to the hair follicle is of great interest. Therefore the influence of permeant lipophilicity and vehicle composition on local accumulation has been examined using confocal laser scanning microscopy (CLSM). Formulations saturated with either Oregon Green^® 488, Bodipy^® FL C₅ or Bodipy^® 564/570 C₅ were prepared. The dyes were applied in citric acid buffer, 8% (w/v) surfactants in citric acid buffer or 8% (w/v) surfactants/20% (w/v) propylene glycol in citric acid buffer. Flow-through diffusion experiments were performed with fresh human scalp skin, after which the skin was imaged using CLSM. Diffusion studies showed for Oregon Green^® 488 (low lipophilicity) a higher flux when applied in citric acid buffer compared to surfactants. In contrast the fluxes of the more lipophilic dyes (Bodipy^® FL C₅ and Bodipy^® 564/570 C₅) are highest when applied in surfactants/propylene glycol. CLSM studies revealed that follicular accumulation increased with (i) a lipophilic dye and (ii) application of lipophilic dyes in surfactants–propylene glycol. Therefore we conclude that targeting to the hair follicle can be increased by the use of lipophilic drugs in combination with surfactant solutions and propylene glycol.     

核因子-κB p65在宫颈癌组织中的表达及意义

 目的　探讨NF κBp6 5蛋白在宫颈鳞癌及宫颈腺癌组织中表达的意义。 方法　采用免疫组织化学方法 ,用NF κBp6 5单克隆抗体检测 6 4例宫颈鳞癌组织 ,6例宫颈腺癌组织 ,11例宫颈上皮内瘤样病变 (CIN)组织 ,16例慢性宫颈炎组织中NF κBp6 5的表达。 结果　NF κBp6 5在宫颈鳞癌和腺癌中的阳性表达明显高于CIN和慢性宫颈炎组织 ,有淋巴转移的癌组织中NF κBp6 5的阳性表达率高于无淋巴转移的癌组织。结论　NF κBp6 5蛋白在宫颈癌的发生发展中起重要作用     

Ewing’s肉瘤细胞X-射线照射后TNF-α和TGF-β mRNA表达的研究

 目的　研究Ewing’s肉瘤细胞系 (RM 82 )X 射线外照射后肿瘤坏死因子 (TNF α)和转化生长因子 (TGF β)mRNA表达水平的变化 ,探讨X 射线诱导内源性TNF α和TGF β产生的可能性及意义。 方法　应用实时荧光RT PCR ,检测接受不同剂量X 线照射 (2Gy ,5Gy ,10Gy ,2 0Gy ,30Gy ,4 0Gy)和受照后不同时间 (1h ,3h ,6h ,12h ,2 4h ,4 8h ,72h)。TNF α和TGF βmRNA表达水平的变化。 结果　RM 82细胞TNF αmRNA表达水平较外照射前显著升高。一方面受照后TNF αmRNA表达逐渐升高 ,照射剂量达 4 0Gy时TNF αmRNA表达水平达高峰 ,为正常对照组的 10 8倍 ;另一方面 ,照射后 3h后TNF αmRNA表达逐渐升高 ,6h达高峰 ,为正常对照组的 18倍。相反 ,TGF βmRNA表达水平X 射线照射前后无显著变化。结论　Ewing’s肉瘤细胞系 (RM 82 )接受X 线照射后TNF αmRNA表达明显升高 ,且呈现时间、剂量依赖性。放射治疗可诱导Ewing’s肉瘤细胞系 (RM 82...     

聚乙二醇修饰水蛭素的分离纯化与活性分析

用活化的聚乙二醇(PEG)对水蛭素进行化学修饰，质谱分析表明，修饰产物是修饰度不同的分子质量相差5000u的水蛭素的混合物。用离子交换层析和凝胶过滤层析对反应产物进行分离纯化，离子交换层析难以达到完全分离；而采用凝胶过滤层析方法可较好地分离修饰度不同的各组份。生物学活性分析表明，不同的PEG修饰度对水蛭素的活性具有显著影响，连接1～2个PEG的水蛭素保持了原有活性，而连接3个PEG的水蛭素活性显著下降。     

聚乙二醇4000治疗出口梗阻型便秘的临床疗效观察

目的　评价聚乙二醇 4 0 0 0 (PEG 4 0 0 0 )治疗出口梗阻型便秘 (OOC)的临床疗效。方法　采用随机对照试验方法 ,选择OOC 6 9例 ,随机分为治疗组 (36例 )和对照组 (33例 ) ,分别接受PEG 4 0 0 0和乳果糖治疗 ,疗程 4周并评估其疗效。总体疗效评估采用模拟视觉梯度的评分方法 (1 0 0mmVAS)。结果　治疗 2周和 4周后 ,二组每周排便次数较治疗前均显著增加 ,大便性状、排便困难和直肠排空感均也比治疗前明显改善 (P <0 .0 1 ) ,但二组间差异无显著性 (P <0 .0 5 ) ,其中大便性状改善PEG 4 0 0 0明显优于乳果糖 (P <0 .0 5 )。大便性状恢复正常比例治疗组大于对照组 (治疗 2周和 4周后 ,分别为 75 .0 %和 83.3%比 5 1 .5 %和 6 0 .6 % ,P <0 .0 5 )。PEG 4 0 0 0组 1 0 0mmVAS评分为75 .3,显著高于乳果糖组的 5 4 .8(P <0 .0 5 )。结论　聚乙二醇 4 0 0 0治疗出口梗阻型便秘安全有效     

羟基磷灰石植入物眼窝成形及装钉术

目的 观察羟基磷灰石(HA)植入物眼窝成形及二期钻孔装钉术的疗效。方法 将同期HA植入物眼窝成形37例37眼按手术方式不同分为两组。A组21例采用HA植入物眼窝成形及二期钻孔装钉术；B组16例采用单纯HA植入眼窝成形术，未行二期钻孔装钉术。比较分析两组术后义眼活动度及并发症。结果 经随访3～48月(平均19．6月)，A组疗效满意，仅1例上睑沟凹陷，B组义眼活动度差，出现各种并发症11例。结论 HA植入物眼窝成形及二期钻孔装钉术疗效明显优于未装钉者，是矫正眼窝凹陷和改善义眼活动度的理想手术方法。     

锑掺杂纳米二氧化锡颗粒在乙二醇中的分散稳定性

开发了二次球磨湿法制备锑掺杂纳米二氧化锡(ATO)/乙二醇(EG)稳定体系的新方法;选用硅烷偶联剂KH 570,实现了ATO颗粒在EG溶液中的均匀分散和稳定性控制;研究了分散工艺参数对体系的影响,探讨了ATO颗粒的表面包覆改性机理。研究表明:分散剂KH 570的含量和体系的pH显著影响ATO在EG中的分散稳定性,在KH 570含量为1.5%,体系pH为8.5时,ATO/EG浆料的分散性能最佳。KH 570与ATO颗粒表面羟基发生的化学键结合,提高了颗粒表面的疏水性,改善了ATO颗粒与有机极性溶剂及高聚物之间的亲和力。     

18β-甘草次酸聚乙二醇轭合物的合成及其体外抗肿瘤活性

将18β-甘草次酸的C20位上的羧基与氨基聚乙二醇的氨基缩合形成了18β-甘草次酸的聚乙二醇轭合物,并用紫外和红外波谱分析等手段证实了该轭合物的结构。实验中发现,18β-甘草次酸的聚乙二醇轭合物的水溶性比18β-甘草次酸高280倍左右;使用B16小鼠黑色素瘤细胞测定了该轭合物的抗肿瘤活性,结果表明:其抗肿瘤活性与对照物18β-甘草次酸相当。良好的水溶性和生物活性表明18β-甘草次酸的聚乙二醇轭合物是一种具有良好应用前景的抗肿瘤药物。     

线型和星型聚乙二醇-聚己酸内酯两亲嵌段共聚物聚集行为

分别以单甲氧基聚乙二醇和4臂聚乙二醇引发己酸内酯开环聚合制得线型和星型聚乙二醇-聚己酸内酯(PEG-PCL)两亲嵌段共聚物。IR1、H-NMR和GPC测试结果表明所合成的共聚物具有预期的结构。该PEG-PCL两亲嵌段共聚物中PEG组分具有结晶性。共聚物在水相中自组装形成聚集体,聚集体的水合直径小于50 nm。高浓度共聚物在水性介质中会发生凝胶-溶胶转变,在凝胶-溶胶转变温度以下,共聚物形成凝胶网状结构。共聚物中PEG组分的结晶性、在水相中生成的聚集体的水合直径以及凝胶-溶胶转变行为均与聚合物的组成以及分子形状密切相关。