THE PHARMACOLOGICAL ROLE OF P-GLYCOPROTEIN IN THE INTESTINAL EPITHELIUM

P-glycoprotein, a membrane-associated transport protein, has recently been recognised as an important element of the intestinal epithelium. This paper summarises thein vivodata on the pharmacological role of intestinal P-glycoprotein. These data show that P-glycoprotein contributes to the elimination of many drugs by mediating their direct secretion from the blood into the intestinal lumen. In addition, there is also evidence that this protein can limit oral drug absorption. Hence, inhibition of intestinal P-glycoprotein, e.g. by a reversal agent like cyclosporin A, may be a promising strategy for improving the oral bioavailability of P-glycoprotein substrate drugs. Indeed, several preclinical and clinical studies have shown that coadministration of drugs with a reversal agent can substantially increase oral drug absorption.     

多种肿瘤标志物联合检测肺癌的临床意义

目的 评价血清肿瘤标志物甲胎蛋白(AFP)、癌胚抗原(CEA)、糖类抗原50(CA50)、糖类抗原19—9(CA19—9)、铁蛋白(SF)、神经元特异性烯醇化酶(NSE)、细胞角蛋白19片段(CYFlRA21—1)水平对肺癌诊断的临床价值。方法 测定72例肺癌患者和40例良性肺病患者的血清AFP、CEA、CA50、CA19—9、SF、NSE、CYFRA21—1水平，比较两组的差异。结果 肺癌组患者CEA、CA50、CA19—9、SF、NSE、CY—FRA21—1水平高于良性肺病组，AFP对肺癌的诊断价值不大。NSE CYF、RA21—1的联合检测具有良好的阳性和阴性预测值。六项联合检测的敏感性和准确性最高，但与两项联合检测的敏感性和准确性差异无统计学意义。结论 NSE CYFRA21—1的联合检测具有良好的临床应用前景。     

肾移植患者的多药耐药基因外显子26基因型与术后他克莫司用量的关系

目的研究肾移植患者的多药耐药基因(MDR1)外显子26(exon26)的基因型与术后他克莫司(FK506)用量的关系。方法回顾106例肾移植术后常规使用FK506患者的临床资料。肾移植患者MDR1 exon26基因分型的方法为:提取患者的DNA,采用聚合酶链反应(PCR)扩增MDR1基因,检测限制性内切酶片段的多态性(RFLP)。根据MDR1 exon26基因分型将患者分为CC、CT和TT 3组。检测各组患者肾移植后第3、6和12个月的FK506血药浓度,比较各组患者FK506血药浓度／FK506用量(μg·L-1／mg·kg-1·d-1)的比值及术后1个月内的急性排斥反应发生率。结果受者经MDR1 exon26基因分型示:CC型32例(30．2％),TT型30例(28．3％),CT型44例(41．5％)。CC型患者FK506血药浓度／FK506用量的比值明显低于CT型和TT型(P<0．01),而CT型患者又低于TT型(P<0．05)。CC型患者的排斥反应发生率明显高于CT和TT型(P<0．05),CT与TT型比较,差异无统计学意义(P>0．05)。结论MDR1 exon26 CC型的患者与CT或TT型比较,需服用更高剂量的FK506才能取得与CT或TT型相似的血药浓度。因此,了解患者的MDR1 exon26基因型有利于指导患者肾移植术后个体化用药。     

部分创面外用抗菌药物与成纤维细胞生长因子2、表皮生长因子、重组人生长激素对成纤维细胞生物学特性影响的实验研究

目的观察部分创面外用抗菌药物与成纤维细胞生长因子(FGF)2、表皮生长因子 (EGF)、重组人生长激素(rhGH)对成纤维细胞生物学特性的影响。方法体外培养成纤维细胞, 按所加药物不同分为对照组(常规培养)、丁胺卡那霉素(0．021、0．210、2．100 mg/L)组、庆大霉素(5、 50、500 mg/L)组、氯霉素(0．01、0．10、1．00 mg/L)组、磺胺米隆(5、10 g/L)组、FGF2(2 400 U/ml)组、 EGF(2 000 U/ml)组及rhGH(0．016、0．160、1．600 g/L)组。用噻唑蓝(MTT)法测定各组成纤维细胞增殖活性[吸光度(A)值],用流式细胞仪检测细胞周期,并于显微镜下观察细胞形态的变化。结果 (1)MTT法检测:与对照组A值0．455 3±0．021 7比较,各种剂量丁胺卡那霉素组、庆大霉素组、氯霉素组、磺胺米隆组成纤维细胞A值均明显降低(P<0．05或0．01),其中磺胺米隆(5、10 g/L)组降低最明显,分别为0．101 3±0．001 1、0．095 0±0．004 1(P<0．01)。FGF2组及0．016 g/L rhGH 组细胞A值明显高于对照组(P<0．05),而EGF组及0.160、1．600 g/L rhGH组A值与对照组接近 (P>0．05)。(2)细胞周期检测:对照组细胞增殖指数(PI)为(9．63±0．45)％,与之比较,0．210 mg/L丁胺卡那霉素组细胞PI值无明显变化(P>0．05),FGF2组、EGF组及0．016 g/L rhGH组PI值均明显升高,分别为(46．76±2．33)％、(42．30±1．41)％、(13．29±0．47)％(P<0．05或0．01)。 (3)形态学观察:对照组、EGF组及0．160、1．600 g/L rhGH组成纤维细胞数目较多,呈长条形或梭形, 轮廓不清,透明度高;丁胺卡那霉素组、庆大霉素组、氯霉素组、磺胺米隆组细胞数目较少,形态不规则,轮廓清晰,透明度低,细胞内多有颗粒样物质及空泡;FGF2组、0．016 g/L rhGH组细胞分布均匀、密集,呈长条形或梭形,核分裂相多见,轮廓不清,透明度高。结论不同创面外用药物对成纤维细胞生物学特性的影响各异,在创面修复过程中应选择合适的创面外用药物,以促进愈合并抑制瘢痕增生。     

人胎肌来源的生物因子抗肿瘤活性实验研究

研究人胚胎横纹肌条件培养液产生的生物因子（ＡＴＰ－ＦＭＣＭ）抗瘤活性。观察发现ＡＴＦ对８种肿瘤细胞株体外增殖有抑制作用。对ＢＧＣ－８２３等６种瘤细胞的抑制率均有５２％￣９４％之间。其中对ＢＧＣ－８２３、Ｖ－７２２１和Ｈｅｌａ３株瘤细胞的抑制率最高，分别为９４％、９３％和８５％。整体抑瘤实验证实，ＡＴＦ能明显减轻Ｓ－１８０荷瘤小鼠腹水的严重程度，生存时间延长，并能有效抑制ＬＡ－７９５肺腺癌荷瘤小鼠的     

Early diagnosis of n-hexane–caused neuropathy

n-Hexane neuropathy was studied in 20 workers exposed for prolonged periods to this solvent, and with urinary 2, 5-hexanedione concentrations exceeding the biological exposure index recommended by the American Conference of Governmental Industrial Hygienists (5 mg/L) with a mean of 11.02 mg/L (range 5.3—24.2 mg/L). Although neurological examination did not detect significant anomalies in any of the patients, and the conduction velocity and F waves of all the nerves tested were normal, neurographic studies revealed significant differences in the amplitude of sensory nerve action potentials (SNAP) recorded from the sural (mean 14.0 μV), median (mean 17.3 μV), and ulnar (mean 7.9 μV) nerves when compared with normal values from healthy adults of the same age range, examined under identical conditions. The amplitude of the SNAP in sural and median nerves correlated significantly with the number of years worked. The notable decrease in mean amplitude of the SNAP appeared to reflect the primary neurotoxic effects of 2,5-hexanedione. © 1994 John Wiley & Sons, Inc.     

Toluene vapor exposure and urinary excretion of hippuric acid among workers in China.

A factory survey was conducted in three provinces in China from 1985 to 1989. The time-weighted average toluene concentrations in breathing zone air were monitored by diffusive sampling, whereas hippuric acid (HA) concentrations in shift-end urine samples were measured by high performance liquid chromatography (HPLC). Exposed workers (456 men and women) were those for whom toluene (up to 548 ppm toluene) accounted for greater than or equal to 90% of total exposure (by vapor concentration in ppm), whereas 517 nonexposed controls were recruited from the same factories or from factories of the same region. There was a linear correlation between the intensity of toluene exposure and HA concentration in the shift-end urine. Comparison of the results with findings in the literature shows that the toluene-induced increase in urinary HA concentration among workers in China is significantly smaller than the published values, whereas HA concentrations in urine samples from nonexposed controls are comparable to the levels previously reported.     

冶金炼铁炉前工人职业性皮损调查研究

冶金炼铁炉前工人职业性皮损调查研究关虹，王溪鸿，杨玉萍（辽宁省本溪钢铁公司劳动卫生研究所，１１７０２１）作者对炼铁炉前工人＂熊猫眼＂样皮损病因及特异部位皮损进行研究，为改善劳动条件，防治职业性皮肤病提供一些依据。以某炼铁厂５号炉前工人为观察组，以炼钢...     

医院感染常见细菌分布与耐药性分析

目的了解细菌分布及常见细菌的耐药性。方法回顾性分析某院2000—2004年临床标本分离的细菌及其耐药性监测结果。结果1439株细菌中，革兰阳性菌456株（31．69％），以凝固酶阴性表皮葡萄球菌为多，达206株（45．18％），其次为金黄色葡萄球菌92株（20．18％）；两种葡萄球菌的耐药率相似，对万古霉素耐药率均为0。革兰阴性菌983株，前5位依次为肠杆菌属346株（35．20％），克雷伯菌属164株（16，68％），铜绿假单胞菌155株（15．77％），埃希菌属101株（10．27％），变形杆菌属94株（9．56％）；前5位革兰阴性菌对常用抗菌药物的耐药性以半合成青霉索较明显，铜绿假单胞菌的耐药性较突出。结论应高度重视细菌变迁和耐药性监测，提高抗菌药物合理应用水平。