Effects of Carbamazepine on Murine Humoral and Cellular Immune Responses

Summary: Oral administration of carbamazepine (CBZ)(15, 10, or 5 mg/kg) to mice significantly decreased both humoral and cellular immune responses evaluated by enumeration of direct and indirect plaque-forming spleen cells (PFC) and delayed–type hypersensitivity reaction (DTH) against sheep red blood cells (SRBC) as compared with those observed in normal control animals. Moreover, spleen T cells obtained from CBZ–treated donor mice were capable of decreasing both PFC and DTH responses of normal spleen cells transferred into lethally irradiated recipient animals. The immunodepressor effect of CBZ was observed even though administration of CBZ induced augmentation of spleen cellularity.     

Pharmacological effects of epibatidine optical enantiomers

The pharmacology of synthetic - and -epibatidine, an alkaloid originally characterized from frog skin, were studied in different behavioral tests in mice and rats. The two enantiomers have potent antinociceptive activity in mice using the tail-flick test, with an ED₅₀ of 6.1 and 6.6 μg/kg for - and -epibatidine respectively. Epibatidine enantiomers were 200 × more potent than -nicotine as an antinociceptive agent in mice after s.c. administration. Their analgesic effect was blocked by mecamylamine but not naloxone, an opiate antagonist. Both - and -epibatidine have high affinity (K_i 54.7 and 55.0 pM, respectively) for [³H]nicotine binding site in rat brain. In addition, they reduced mice locomotor activity and body temperature in a dose-dependent manner. In rats trained with nicotine (0.4 mg/kg), epibatidine enantiomers engendered nicotine-like responding in a dose-related manner with an ED₅₀ of 1.00 and 0.93 μg/kg for and , respectively. The discriminative effect of - and -epibatidine in rats was blocked by mecamylamine but not by hexamethonium. As in binding results, there was no significant enantioselectivity for these effects in our study.     

战伤绿脓杆菌感染源及防治研究

本文对云南老山前、后方医院环境及战伤感染标本中绿脓杆菌(简称PA)进行调查,对所分离的333株PA进行血清学分型及药物敏感性测定。结果可看出除炸伤时创口易被泥土中PA污染外,前、后方医院环境也是感染源之一。提示各级医疗单位在战伤救治中对PA的监控十分重要。本文结果直接有益于前、后方医院对战创伤PA的防治。     

Anticonvulsant Activities of 4–Bromobenzaldehyde Semicarbazone

Summary: Some of the properties of 4–bromobenzalde-hyde semicarbazone (compound IV), a prototype molecule of a new class of anticonvulsants, aryl semicarbazones, are described. Compound IV demonstrated activity in the maximal electroshock (MES) and subcutaneous pentylenetetrazol (scPTZ) tests in mice, with low neurotoxicity. When given orally to rats, it displayed high potency in the MES test and very low neurotoxicity, resulting in a high protective index (PI). Compound IV displayed no proconvulsant properties, and development of rapid tolerance was not noted. When administered intraperitoneally (i.p.) at doses of 100, 300, or 600 mg/kg to rats, compound IV had no effect on levels of γ-aminobu-tyric acid (GABA) or on GABA-T activity in whole brain. When tested in vitro, compound IV had no effect on rat brain GABA-T at a drug concentration of 100 μM. Although the activities of certain drug-metabolizing enzymes were increased after oral administration of compound IV to rats, these effects were less prominent than those of phenytoin (PHT) and carbamazepine (CBZ). The principal mode of action of compound IV does not appear to be an interaction with the GABA_A receptor complex, and other mechanisms, involving excitatory amino acid neurotransmission, will have to be considered in future investigations of the anticonvulsant activity of this compound.     

When poor solubility becomes an issue: From early stage to proof of concept

Drug absorption, sufficient and reproducible bioavailability and/or pharmacokinetic profile in humans are recognized today as one of the major challenges in oral delivery of new drug substances. The issue arose especially when drug discovery and medicinal chemistry moved from wet chemistry to combinatorial chemistry and high throughput screening in the mid-1990s. Taking into account the drug product development times of 8–12 years, the apparent R&D productivity gap as determined by the number of products in late stage clinical development today, is the result of the drug discovery and formulation development in the late 1990s, which were the early and enthusiastic times of the combinatorial chemistry and high throughput screening. In parallel to implementation of these new technologies, tremendous knowledge has been accumulated on biological factors like transporters, metabolizing enzymes and efflux systems as well as on the physicochemical characteristics of the drug substances like crystal structures and salt formation impacting oral bioavailability. Research tools and technologies have been, are and will be developed to assess the impact of these factors on drug absorption for the new chemical entities.

The conference focused specifically on the impact of compounds with poor solubility on analytical evaluation, prediction of oral absorption, substance selection, material and formulation strategies and development. The existing tools and technologies, their potential utilization throughout the drug development process and the directions for further research to overcome existing gaps and influence these drug characteristics were discussed in detail.     

东乡族及回族吸毒人群性激素水平的变化

本文测定了东乡族、回族吸毒者血清睾酮及促黄体生成素含量，发现血清睾酮含量吸毒组（ｎ＝４０，Ｘ＝３４０．１４±１０１．４９ｎｇ／ｄＬ）显著低于非吸毒组（ｎ＝４２，Ｘ＝４４４．５０±９８．８３ｎｇ／ｄＬ），Ｐ＜０．０１。未观察到ＬＨ含量的改变。戒毒期２０日以内组血清睾酮含量（ｎ＝１６，Ｘ＝２９７．９３±７８．２２ｎｇ／ｄＬ），低于戒毒期２０～６０日组（ｎ＝１７，Ｘ＝３８６．２９±８９．４５ｎｇ／ｄＬ），Ｐ＜０．０１。询问１０３名吸毒者，２月后性欲下降２５人（２４．２７％），增强２人（１．９４％），无变化１３人（１２．６２％），不愿回答者６３人（６１．１７％）。吸毒影响性功能，损害性健康。     

对曾氏推导的药物蛋白结合率公式的修正

对曾氏推导的药物蛋白结合率公式的修正娄建石（天津医科大学药理教研室，天津３０００７０）测定药物蛋白结合率是药物代谢动力学研究中的重要内容之一。曾衍霖教授根据国外文献推导出药物蛋白结合率公式（１），为这方面的研究提供了很好的计算依据。本文作者在计算药物...     

Oral self-administration of etonitazene in rhesus monkeys: Use of a fading procedure to establish etonitazene as a reinforcer

The establishment of orally delivered etonitazene (a potent opioid) as a reinforcer, was studied in eight rhesus monkeys. Initially, when given concurrent access to 2.5 μg/ml etonitazene and the water vehicle, five of the monkeys rejected the drug, whereas the other three monkeys consumed more drug solution than water. The five monkeys that rejected the drug solution underwent an acquisition phase to establish the drug as a reinforcer. A fading procedure was used to transfer control of responding from a 2% (wt/vol) ethanol solution to a 2.5 μg/ml etonitazene solution. Initially, responding was maintained by contingent deliveries of 2% ethanol. Next, across blocks of six or more sessions, increasing amounts of etonitazene were added in steps to the 2% ethanol solution. Subsequently, the 2% ethanol solution was decreased in steps to zero, leaving only the 2.5 μg/ml etonitazene present. When the fading procedure was completed, dose of etonitazene was varied by increasing the volume delivered, first under fixed ratio (FR 4) and then under an FR 8 reinforcement schedule. The same dose manipulations were made with the three monkeys who did not undergo the fading procedure because they preferred etonitazene over water when first tested. Etonitazene was established as a reinforcer for six of the eight monkeys because drug deliveries exceeded vehicle deliveries across a range of drug doses.     

自乳化释药系统的体外评价

目的 探讨自乳化释药系统的体外评价方法。方法 通过测定自乳化时间、乳化后乳剂粒径的大小及模型药物的体外溶出行为对自乳化释药系统进行体外评价。结果 优选出的自乳化处方10min内已基本乳化完全，乳化后乳剂粒子大小大多数在3μm左右，以吲哚美辛和尼莫地平为模型药物制备出自乳化释药系统，体外溶出结果表明：与混悬液相比，两种药物的体外溶出显提高。结论 自乳化释药系统能够提高难溶性药物的体外溶出。