Codeine-induced histamine release in intact human skin monitored by skin microdialysis technique: comparison ofintradermal injections with an atraumatic intraprobe drug delivery system

Background The skin microdiallysis technique makes it possible to measure histamine release in intact human skin in vivo directly. In this study we have used the microdialysis technique to characterize histamine release by codeine after intracutaneous injectioin and following skin challenge by a novel atraumatic delivery technique. Objective The purpose of the study was to compare histamine release in human skin by codeine. delivered by an intraprobe drug delivery system (IPD) and intracutaneous injections (ICT), with respect to dose-response relations, kinetics of histamine appearance and decay, corelations between histamine release and skin respones, and reproducibility. Methods Hollow dialysis fibres were inserted intradermally in 12 healthy subjects. Twelve fibres were inserted in each subjects, six fibres in each arm. Each fibre was perfused at a rate of 3 μL/min, and samples were collected in 2 min fractions. By the IPD technique, codeine was administrered to the skin by adding codeine to the perfusion medium. Sequential IPD challenges were performed in one arm. and ICTs were done on the other arm. Results Sixfold serial dilutions of codeine (0.01-3 mg/mL) caused a significant doserelated histamine release by ICT and IPD. Peak histamine release was found within the first 4 min after skin challenge by ICT and IPD, followed by a fast decline with a dialysate histamine half life of approximately 2-3 min. Peak hisamine release was linearly correlates with cumulative release of the 20 min sampling period, and histamine release correlated with weal soze. The coefficient of variation on peak histamine releae was 18.9% and 4.8% for codeine ICT and IPD, respectively. Conclusioin We have described in detail codeine-induced histamine release in intact human skin in vivo by the microdialysis technique. It was possible to administer codeine atraumaticallyl to the skin by intraprobe delivery. The skin microdialysis codeine atraumaticallly to the skin by intraprobe delivery. The skin microdialysis technique opens up possibilities for measurement of infllammatory mediators release in normal and diseases skin, and it will be possible to deliver immunopharmacologically active drugsto the skin by intraprobe delivery.     

Safety pharmacology of the respiratory system: Techniques and study design

The known effects of drugs from a variety of pharmacologic/therapeutic classes on the respiratory system and worldwide regulatory requirements support the need for conducting respiratory evaluations in safety pharmacology. The objective of these studies is to evaluate the potential for drugs to cause secondary pharmacologic or toxicologic effects that influence respiratory function. Changes in respiratory function can result either from alterations in the pumping apparatus that controls the pattern of pulmonary ventilation or from changes in the mechanical properties of the lung that determine the transpulmonary pressures (work) required for lung inflation and deflation. Defects in the pumping apparatus are classified as hypo- or hyperventilation syndromes and are evaluated by examining ventilatory parameters in a conscious animal model. The ventilatory parameters include respiratory rate, tidal volume, minute volume, peak (or mean) inspiratory flow, peak (or mean) expiratory flow, and fractional inspiratory time. Defects in mechanical properties of the lung are classified as obstructive or restrictive disorders and can be evaluated in animal models by performing flow-volume and pressure-volume maneuvers, respectively. The parameters used to detect airway obstruction include peak expiratory flow, forced expiratory flow at 25 and 75% of forced vital capacity, and a timed forced expiratory volume, while the parameters used to detect lung restriction include total lung capacity, inspiratory capacity, functional residual capacity, and compliance. Measurement of dynamic lung resistance and compliance, obtained continuously during tidal breathing, is an alternative method for evaluating obstructive and restrictive disorders, respectively, and is used when the response to drug treatment is expected to be immediate (within minutes post-dose). The species used in the safety pharmacology studies conducted in our laboratory are the same as those used in toxicology studies since pharmacokinetic and toxicologic/pathologic data are available in these species. These data can be used to help select test measurement intervals and doses and to aid in the interpretation of functional change. The techniques and procedures for measuring respiratory function parameters are well established in guinea pigs, rats, and dogs.     

Single-dose oral omeprazole for reduction of gastric residual acidity in adults for outpatient surgery

Omeprazole is a substituted benzimidazole that causes dose-dependent intracellular inhibition of gastric acid secretion in humans. This double-blind study examined the effect of omeprazole in decreasing gastric acidity and gastric residual volume in outpatient adults. Unpremedicated outpatients, ASA I-III, 18 years or older (n = 17), were randomly assigned to receive omeprazole 80 mg, or placebo by mouth the night before scheduled elective outpatient surgery. The patients were fasted for 8 h prior to surgery. After the patient was anesthetized, an orogastric tube was inserted with proper placement verified by auscultation for gastric sounds. Gastric residual contents were withdrawn into a Luken's trap, and pH was then determined and gastric volume indexed to weight (ml.kg-1). Data were analyzed by a t-test, with P less than 0.05 considered statistically significant. Patient characteristics of both groups were similar. There was a statistically significant difference between the two groups for pH (P = 0.02), but not between the two groups for gastric volume indexed to weight (P = 0.07).     

我国学术期刊如何应对加入WTO后的机遇与挑战

针对目前我国学术期刊的发展现状及存在的问题，探讨入世对学术期刊出版的影响，并对我国学术期刊业如何应对入世的挑战提出相应的发展对策和措施。     

中草药醛糖还原酶抑制剂筛选模型的建立

目的：通过观察中药知母对醛糖还原酶活性的抑制作用，建立一种适用于筛选中草药醛糖还原酶抑制剂的模型。方法：大鼠12只随机分成3组：空白对照组、知母组、阳性药物组，分别给予生理盐水、知母水提液、依帕司他水溶液灌胃。采用“通法”给药方案制备含药血清，部分血清经过丙酮预处理。将知母水提液和含药（知母）血清分别加人体外建立的以DL-甘油醛为底物、NADPH为辅酶的醛糖还原酶活性测定体系。结果：丙酮处理过的空白血清较未处理的空白血清对酶活性的影响更小；知母水提液对醛糖还原酶抑制率达99％，含药（知母）血清对醛糖还原酶抑制率达67％。结论：运用血清药理学实验方法建立的筛选模型能有效、可靠的进行中草药醛糖还原酶抑制剂的筛选。     

微型无线收发器在中央监护系统中的应用

中央监护系统能够实现对病人的生理或生化参数连续、长时间、自动、实时监测，并经分析、处理后实现多类别自动报警、自动记录及对诊断结果进行综合判断等。传统的多参数生理监护系统主要是通过各种专用电缆来实现网络化，在增加产品成本的同时也加大了施工的难度。本文在分析了无线收发芯片XE1201的工作原理基础上，重点介绍了应用其开发无线收发模块的原理和方法，并利用此模块构建了无线中央监护系统，继而对整个系统的性能进行了测试。该系统已在实验室中实现，并对心电(ECG)、无创血压、血氧饱和度(SPO2)等多生理参数进行实时监护，将信息提供给医院内的网络，以供访问使用。     

Schedule-controlled brain self-stimulation: Has it utility for behavioral pharmacology?

We review evidence that schedule-controlled intracranial self-stimulation (ICSS) has properties in common with conventional reinforcements, such as food and water, but unlike the latter, animals will respond for ICSS for long periods of time at a near-constant rate. Schedule-controlled ICSS has proven to be more sensitive to drug-induced changes than has ICSS on a continuous reinforcement schedule, and it permits a more fine-grained analysis of the pattern of responding that results in the reinforcement. Evidence is accumulating that the schedule of ICSS itself leads to neurochemical changes in areas of the brain, such as the nucleus accumbens, in which reward processes occur. Results obtained from schedule-controlled ICSS would complement those obtained by drug self-administration studies which generally use intermittent reinforcement. A systematic examination of ICSS schedules at different brain sites would greatly facilitate our interpretation of drug effects and this would have utility for behavioral pharmacology.     

Different effects of halothane, isoflurane and sevoflurane on sarcoplasmic reticulum of vascular smooth muscle in dog mesenteric artery

Background: The direct effect of halothane on vascular smooth muscle is mediated in part via its effects on the sarcoplasmic reticulum (SR). Little information is available concerning the effects of other volatile anesthetics including isoflurane and sevoflurane, whose vascular effects differ from those of halothane. The aim of the present study was to compare the effects of halothane, isoflurane and sevoflurane on the SR by testing the contraction induced by caffeine in vascular smooth muscle. Methods: Rings without endothelium from isolated canine mesenteric artery were mounted in physiological saline solution (PSS) for isometric tension recording. After complete depletion of Ca²⁺ from the SR by adding 35 mM caffeine, the rings were exposed to normal Ca²⁺ containing PSS (Ca²⁺ loading), to Ca²⁺-free PSS for 10 min, and then to 15 mM caffeine to induce contraction. Anesthetics were administered during Ca²⁺ loading, the Ca²⁺-free phase and simultaneously with caffeine administration. Results: Halothane (0.5-2%) attenuated the caffeine-induced contraction of canine mesenteric artery when administered during Ca²⁺ loading in the SR (P<0.001), whereas isoflurane and sevoflurane (1–4%) failed to affect the contraction. When given simultaneously with caffeine, halothane (1–2%) potentiated the caffeine-induced contraction (P<0.05), but isoflurane and sevoflurane had no effect. When given before caffeine administration, halothane (0.5-2%), isoflurane (24%) and sevoflurane (4%) all potentiated the caffeine-induced contraction (P<0.05). Conclusion: It has been shown that halothane not only potentiates caffeine- induced Ca²⁺ release from the SR, but also induces contraction by releasing Ca²⁺ from the SR. We conclude that halothane decreases Ca²⁺ accumulation in the SR while exerting facilitative and additive effects on caffeine-induced Ca²⁺ release from the SR when applied before caffeine administration and simultaneously with caffeine, respectively, whereas isoflurane and sevoflurane lack both the ability to decrease Ca²⁺ accumulation and an additive effect on caffeine-induced Ca²⁺ release from the SR, but are able to facilitate Ca²⁺ release by caffeine.     

论河北省卫生系统办公自动化管理系统

系统采用基于TCP/IP协议的国际互联网为基础,采用B/S结构,客户端采用IE浏览器,服务器端采用WINDOW2000的IIS作为服务器。其主要功能:工作督办、工作信息、电子邮件、收文、发文、图书管理、档案管理、车辆管理、日程管理、待办事宜、电子论坛、考勤管理等。