Biological monitoring of tetrahydrofuran: contribution of a physiologically based pharmacokinetic model

A seven-compartment physiologically based pharmacokinetic (PBPK) model was developed to predict biological levels of tetrahydrofuran under various exposure scenarios. Affinities for the tissue were estimated from measurements of liquid-gas partition coefficients for water, olive oil, and blood. Metabolism was assumed to follow a rapid first order reaction. urinary excretion was simulated considering passive reabsorption of tetrahydrofuran in the tubules. The validity of the model was tested by comparison with available experimental and field data. Agreement was satisfactory with all studies available except one, which showed much higher results than expected. The source of this difference could not be identified, but cannot be explained by different exposure conditions, such as duration, concentration, or physical work load. However, it is recommended that this particular study not be used in the establishment of a biological exposure index. Simulation of repeated occupational exposure with the PBPK model allowed the prediction of biological levels that would be reached after repeated exposure at the American Conference of Governmental Industrial Hygienists' threshold limit value, time-weighted average of 200 ppm. For samples taken at the end of the shift, the PBPK model predicts 5.1 ppm for breath, 57 mumol/L (4.1 mg/L) for venous blood, and 100 mumol/L (7.2 mg/L) for urine.     

Immunohistochemical analysis of Fas ligand expression in normal human tissues

Cross-linking of Fas and Fas ligand (FasL) induces apoptosis in Fas-bearing cells and regulates apoptosis. Fas is widely expressed in normal human tissues, but FasL expression has been considered to be restricted to lymphoid tissues. Recent studies have demonstrated that FasL is also expressed in some nonlymphoid tissues. To screen the in situ expression of FasL in normal human tissues, immunohistochemistry was performed using paraffin-embedded human tissues. FasL immunostaining was easily detected in testis, neurons, trophoblasts, tonsil, lymph node, Paneth cells, hepatocytes, renal tubular epithelium and bronchial epithelium, consistent with previous reports. Surprisingly, FasL was also expressed in many other cell types, including thymic medulla, skeletal muscle, cardiac muscle, pituitary gland, parathyroid gland, prostate glands, oocytes, epithelium of fallopian tube, endometrial glands, and gastric parietal cells. These findings demonstrate that FasL is widely expressed in human tissues and suggest that wide but cell-type specific expression of FasL may not only be implicated in the regulation of immune homeostasis but also in the regulation of cell death and life in many cell types in vivo.     

The inhibitory effect of ambroxol on hypochlorous acid-induced tissue damage and respiratory burst of phagocytic cells

Ambroxol (100 microM and 1 mM) and the thiols (all 1 mM), glutathione, tiopronin and cysteine, significantly attenuated the myeloperoxidase, H(2)O(2) and Cl(-) system-caused destruction of alpha(1)-antiproteinase and the HOCl-induced destruction of collagen, whereas they did not affect the elastase-induced destruction of collagen. Glutathione, tiopronin and cysteine almost completely decomposed both HOCl and H(2)O(2), while ambroxol up to 1 mM did not show a scavenging action on H(2)O(2). Ambroxol (1 to 100 microM) and 1 mM thiol compounds markedly inhibited the HOCl-induced alteration of elastase activity. Thiol compounds significantly attenuated the HOCl production caused by degraded immunoglobulin G-activated neutrophils. Ambroxol depressed superoxide and H(2)O(2) production induced by degraded immunoglobulin G-activated neutrophils and by lipopolysaccharide-activated alveolar macrophages in a dose-dependent manner. The results show that ambroxol may interfere with oxidative tissue damage and decrease proteolytic tissue destruction by attenuation of oxidative stress-induced inactivation of alpha(1)-antiproteinase through both decomposition of HOCl and inhibition of the respiratory burst in phagocytic cells.     

Synthesis of 4-hydroxy-1-thiocoumarin derivatives-1: An efficient synthesis of thioflocoumafen

An efficient procedure for the preparation of 4-hydroxy-3-{1,2,3,4-tetra-hydro-3-[4-(4-triflu-oromethylbenzyl oxy)phenyl]-1-naphthyl}thiocoumarin (thioflocoumafen, 1a and 1b) is described. The key step in the synthesis involves the condensation reaction of 3-(4-methoxyphenyl)-1-tetralol (2) with 4-hydroxy-1-thiocoumarin (3).     

Factors affecting practice-area choices by pharmacy students in the Midwest.

The results of a survey to determine the first-choice practice intentions of midwestern pharmacy students and to describe and quantify the factors affecting their decisions are reported. Questionnaires were sent to 12 pharmacy schools in American Association of Colleges of Pharmacy District IV and distributed during November 1988 to January 1989. The questionnaires were given to entry-level pharmacy students who were in their final year of study. The students were asked to indicate their preferred practice setting upon graduation and to rate the importance of 21 factors that a pharmacist might consider when selecting a first position. A total of 715 usable responses were received (response rate, 6.75%). OF the respondents, 83.2% were enrolled in B.S. degree programs and 16.8% in entry-level Pharm.D. degree programs. The distribution of first choices of a practice area was as follows: chain community pharmacy, 33.1%; hospital pharmacy, 27.6%; independent community pharmacy, 12.4%; industry, 8.4%; "other," 5.5%; ambulatory-care clinic, 5.2%; graduate school, 3.8%; department store, discount store, or grocery store, 1.7%; home health care, 1.5%; and nursing home, 0.8%. The three factors ranked as most important in affecting the choice of a practice area were personal fulfillment, salary, and the opportunity to use one's abilities and education. The ranking of the factors varied depending on the practice area chosen. Midwestern pharmacy students were most interested in chain community and hospital pharmacy practice settings. Retail-oriented students placed salary concerns first, whereas clinically oriented students emphasized personal fulfillment. These findings have implications for recruitment strategies.     

内皮素、一氧化氮在毛细支气管炎和哮喘患儿中的变化

目的　 探讨血内皮素 (ET)和一氧化氮 (NO)在毛细支气管炎 (毛支 )和婴幼儿哮喘 (哮喘 )中的变化及意义。 方法 　用放射免疫分析法和分光光度比色法分别检测毛支、哮喘患儿急性期和缓解期血ET和NO ,并与正常儿童进行比较。 结果 　血浆ET在毛支组和哮喘组 ,急性期均明显高于正常组 (P均 <0 0 1) ,缓解期均下降 ,与正常组比较无显著差别 (P均 >0 0 5 ) ;两组急性期比较无差别 (P >0 0 5 )。与血浆ET一样 ,血清NO在毛支组和哮喘组 ,急性期均显著高于正常组 (P <0 0 1和P <0 0 5 ) ;缓解期则下降 ,与对照组比无显著差别 ,(P均 >0 0 5 ) ;两组急性期相比 ,差异无显著性 (P >0 0 5 )。两组急性期血浆ET与血清NO呈明显正相关 (P <0 0 5 )。 结论 　在毛支和哮喘中 ,血ET和NO均升高 ,二者关系密切 ,均可能参与毛支及哮喘的发病     

PCR快速鉴定actinobacteria三种模板制备方法的比较

目的 本研究旨在建立准确、简便、快速的放线细菌鉴定技术，为普通和极端环境放线细菌资源的调查和开发利用创造条件。方法 从放线细菌固体培养基上挑取少量菌体，用微波炉法快速制备基因组DNA作为PCR模板，与液体培养法得到的菌体以超声波法或冻融法制备的模板进行了PCR扩增效果的比较研究。结果P CR检测结果表明微波炉法制备的模板可进行有效的体外扩增，目的条带特异，而超声波法或冻融法并不对所有菌株有效，并有非特异扩增产物产生。结论 组合微波炉法快速制备放线细菌基因组DNA技术和23S rRNA特异插入序列PCR扩增技术建立了准确、简便、快速的actinobacteria鉴别体系。     

HPLC法测定复方联苯双酯颗粒中肌苷的含量

目的:应用HPLC色谱法测定复方联苯双酯颗粒中肌苷的含量.方法:采用C8柱以甲醇-水(60:40)为流动相,检测波长为248 nm.结果:肌苷线性范围为2.50～25.00μg·ml-1,r=0.999 97(n=6).肌苷平均回收率100.1%,RSD 0.4%(n=9).结论:方法简便,结果准确,重复性好.