Uptake and intracellular distribution of idarubicin in secondary cultures of normal and neoplastic urothelium

This study analyzes the uptake and endocellular distribution of idarubicin (IDA) in normal and neoplastic urothelial secondary cultures in relation to the changes in concentration and time of exposure. The urothelial lines were isolated by Freshney's method from biopsy fragments taken from five patients with superficial bladder cancer. Pharmacological experiments were carried out on subcultures previously immunophenotypically characterized and did not exceed ten passages. The uptake and endocellular distribution of IDA was analyzed by densitometric image analysis on cells treated for 10, 20, 30 and 60 min and 2 h with scalar dosages from 10 ng/ml to 2430 ng/ml. Microscopic observations and densitometric analyzes revealed that in the cells treated with IDA, fluorescence was higher in the cytoplasm compared to the nucleus and increased with the change in dosage. Moreover, densitometric data showed that IDA uptake in the first 20 min was higher in the neoplastic cells, but after that period its behavior became heterogeneous at 30 and 60 min, while at 2 h there was an inversion of the trend. These results suggest that the in vitro cytotoxicity should be evaluated in order to verify whether the elevated uptake of IDA in the first 20 min of treatment is really correlated to a more elevated toxicity in the neoplastic cells with respect to the normal cells. This is presently under investigation.     

天然放射性气溶胶的粒径分布及其测量方法

天然放射性气溶胶粒径分布的变化会引起氡及其子体所致肺剂量的较大涨落。由于我国对其报道甚少，在肺剂量估算中均引用ＵＮＳＣＥＡＲ的推荐值。为验证这种引用的合理性和建立气溶胶粒径分布的测量方法，开展本项研究。方法采用金属丝网筛（１６５目）扩散法测量天然空气经不同数目网筛扩散前后的放射性浓度比（衰减比）来绘制衰减曲线，然后用池边模式计算出粒径分布曲线。衰减比、粒径分布的计算和曲线的绘制均采用计算机。结果室内外天然放射性气溶胶粒径呈几何正态分布，分布的峰值的平均值分别为（０．２０±０．０９）μｍ和（０．２７±０．１１）μｍ。粒径分布和氡浓度、气压、气温、湿度等未发现相关关系。结论本研究结果与ＵＮＳＣＥＡＲ报告书（１９８８）的推荐值相比，室内值相同，室外值略高，与Ｊａｃｏｂｉ的研究相近。由此可得出结论，福州地区引用ＵＮＳＣＥＡＲ报告书的推荐值来估算氡及其子体所致肺剂量是合适的。此结论能否推广到其他地区，还需作进一步的研究。     

Ester und Stereoisomere

This review discusses concepts of isomers, stereoisomers, chirality, and enantiomers as applied to drugs used in anaesthesia. The inhalational anaesthetics enflurane and isoflurane are examples of stereoisomers. A chiral centre is formed when a carbon or quaternary nitrogen atom is connected to four different atoms. A molecule with one chiral centre is then present in one of two possible configurations termed enantiomers. A racemate is a mixture of both enantiomers in equal proportions. Many of the drugs used in anaesthesia are racemic mixtures (the inhalational anaesthestics, local anaesthetics, ketamine, and others). The shape of the atracurium molecule is comparable to that of a dumb-bell: the two isoquinoline groups representing the two bulky ends connected by an aliphatic chain. In each isoquinoline group there are two chiral centres, one formed by a carbon and the other by a quaternary nitrogen atom. From a geometric point of view, the connections from the carbon atom to a substituted benzene ring and from the quaternary nitrogen to the aliphatic chain may point in the same direction (cis configuration) or in opposite directions (trans configuration). The two isoquinoline groups in atracurium are paired in three geometric configurations: cis-cis, trans-trans, or cis-trans. However, the two chiral centres allow each isoquinoline group to exist in one of four stereoisomeric configurations. In the symmetrical atracurium molecule, the number of possible stereoisomers is limited to ten. Among these, 1 R-cis, 1′ R-cis atracurium was isolated and its pharmacologic properties studied. This isomer, named cis-atracurium, offers clinical advantages over the atracurium mixture, principally due to the lack of histamine-releasing propensity and the higher neuromuscular blocking potency. The ester groups appear in one of two steric configurations true and reverse esters. In the true esters, oxygen is positioned between the nitrogen atom and the carbonyl group, while in the reverse esters it is positioned on the other side of the carbonyl group. True esters, suxamethonium and mivacurium, are hydrolysed by the enzyme plasma cholinesterase (butyrylcholinesterase), albeit at different rates. The more rapid degradation of suxamethonium is responsible for its fast onset and short duration of action in comparison with mivacurium. The reverse esters, atracurium, cisatracurium, and remifentanil, are hydrolysed by nonspecific esterases in plasma (carboxyesterases). Remifentanil is hydrolysed rapidly; the degradation leads to its inactivation and short duration of action. Cis-atracurium is preferentially degraded and inactivated by a process known as Hofmann elimination. In a second step, one of the degradation products, the monoester acrylate, is hydrolysed by a nonspecific esterase.     

Heterologous Expression of Rat Testis GABAA Receptor β3t Splicing Variant in CHO Cells

Objective To characterize a possible retention function of unique sequence in the 5'end of rat testis GABAA receptor β3t splicing variantMethods Rat testis GABAA receptor β3t splicing variant cDNA was cloned and two eukaryotic expression recombinant plasmids of pEGFP-N1 and pEGFP-C1 were constructed respectively by fusing green fluorescent protein to the N or C-terminus of β3t isoform. The recombinant plasmids were transfected into CHO cells by calcium phosphate co-precipitation method. Fluorescence microscope and laser confocal microscope were used to analyze localization of β3t in the transfected cells. ConA-Texas-Red was used to label cell ER and the localization of rat testis β3t splicing variant in CHO cells was determined.Results When rat testis β3t splicing variant was expressed in CHO cells, two expression patterns were delineated, the distributions of uniform and mainly discrete intracellular compartments respectively. The chimera product failed to be translocated into the cell surface when expressed in CHO cells; whereas the β3 subunit of rat brain was incorporated into the plasma membrane.Conclusion The inability of β3t to target into the ER may be a consequence of the unique 25 specific amino acid segments in the N terminus.     

在线考试系统设计

作为评价网络学习效果的一个环节，网上考试越来越被人们接受和认同。文章介绍了在线考试系统的功能和结构，并对该考试系统中所用到的关键技术进行了详细的介绍，包括系统的通用性和安全性、题库的建设和管理、随机组卷算法等。     

Arzneimitteltherapie des Reizdarmsyndroms

Zusammenfassung Die Therapie von Reizdarmpatienten ist oft eine Herausforderung, insbesondere wenn ein breites Spektrum von Symptomen vorliegt und anamnestische Hinweise auf Triggerfaktoren, wie diätetische Einflüsse oder Stress, fehlen. Aktuelle pathogenetische Konzepte propagieren Alterationen in ZNS oder Peripherie, die unter Einbeziehung psychologischer (Stress, Angst, Depression) und biologischer Faktoren (postinfektiöse Residuen, subklinische Entzündung) in integrative Krankheitsmodelle eingehen und zur Erklärung nachweisbarer symptomgenerierender Störungen gastrointestinaler Funktionen (Motilität, Hypersensitivität) dienen. Bei fehlenden universal wirksamen oder kausalen Ansätzen orientiert sich die medikamentöse Basistherapie an den führenden Symptomen, insbesondere Schmerz, Diarrhö und Obstipation. Neben etablierten Medikamenten wie Spasmolytika, Opioiden oder Laxantien sind neu entwickelte Substanzen und solche mit primär anderer Indikation (z. B. Antidepressiva) zur differenzierten individuellen Therapie einsetzbar. In Evaluation befindliche, konzeptionell neuartige Ansätze lassen weitere Fortschritte in der Therapie des Reizdarmsyndroms erwarten.     

LDPE／CPE／炭黑三相复合导电体系的电学性能

研究了ＬＤＰＥ／ＣＰＥ／炭黑三相复合导电体系的导性能和电流－电压特性。实验结果表明复合体系具有明显的导电渗滤效应，在共混比ＬＤＰＥ／ＣＰＥ＞５０／５０时，导电性能随ＣＰＥ含量增加而显著提高，这主要是由于炭黑粒子在ＬＤＰＥ和ＣＰＥ两组分分中的分布不均匀性所致。     

二甲苯胺基噻唑的燐光分析法及其吸收分布排泄和动力学研究

二甲苯胺基噻唑与金莲橙OO在pH2.0生成复合物可用氯仿抽提,分离的复合物在盐酸中用锌还原.还原金莲橙有强的燐光,激发波峰302nm,发射波峰442nm,燐光强度与二甲苯胺基噻唑量成正比.用此法研究其在小鼠体内的吸收、分布、排泄及作药物动力学研究.小鼠im二甲苯胺基噻唑10mg/kg后5min,在血、脑、膈、肺、心、肝、脾、肾、尿及胆中都有药物存在.高峰在给药后30min,6h后各组织中还有不少量药物存在,24h内二甲苯胺基噻唑在小鼠尿中排泄25μg,粪便中排泄1.63μg,共计排泄26.6μg,占给药量的9.67%.兔、大鼠、小鼠im二甲苯胺基噻唑10mg/kg后不同时间测血药浓度,作药物动力学分析,其为二室开放模型药物.三种动物的主要动力学参数为:t_(1/2) 126.2,165.4,207.5min;高峰时间35.1,23.5,17.1min;AUC为416.1,298.3,385.2μg-min/ml;廓清率为24,33.7,26ml/min保定宁吸收速率比它快一倍,半吸收期为2.45min,高峰时间为11.7min.     

阿克拉霉素A毫微囊在大鼠体内的组织分布研究＿（1））

本文利用反相高效液相色谱法测定了阿克拉霉素Ａ毫微囊（ＡＣＭ－Ａ－ＮＣ）在大鼠体内各组织的分布．结果表明：阿克拉霉素Ａ在肺、脾、小肠和胸腺分布较多，而心、肝、肾中分布较少．与ＡＣＭ－Ａ水溶液对比研究表明：ＡＣＭ－Ａ－ＮＣ在肺内分布量较其水溶液提高３．６倍，在脾中提高１．４倍，肝中２．２倍，肾中１．６倍，胸脾中１．２倍，大肠１．２倍，小肠１．１倍，心中约１．２倍．