工作作为药物及酒精滥用者有效的干预策略和治疗方法

1Introduction Substanceabusecontinuestobeamongthemostsevereso cialandcostlyhealthproblemsdevastatingindividualsandtheir familiesintheUnitedStates.Initssimplestdefinition,sub stanceabuseisthecontinueduseofalcoholorotherdrugsde spiteknowledgeofhavingapersistentsocial,vocational,psy chologicalorphysicalproblemthatiscausedorexacerbatedby theuseofalcoholorotherdrugs(DSMIV TR,1994).All drugsofabuse,includingalcohol,aretoxicandcannegatively impacteverysysteminthehumanorganism.Protractedsub stance…     

1040例在院病人抗生素一日使用调查报告

目的了解住院病人抗生素使用情况。方法采用横断面调查的方法时我院2005年7月27日所有住院病人抗生素使用情况进行调查。结果抗生素日使用率为34．81％（304／1040），治疗用抗生素占39．67％（144／363），预防用占16．25％（59／363），治疗＋预防占44．08％（160／363），抗生素单用和二联占95．04％（344／363），三联及以上者4．96％（18／363），抗生素日使用种类47种，病原体送检率7．57％（23／304）。结论我院抗生素日使用率不高，抗生素联合使用总体较好，但仍有病原送检率低、抗生素使用品种多、起点高、部分囤术期抗生素预防用药的时机不合理等现象，建议加强宣传教育力度，提高监测速度和指导医师合理用药。     

西咪替丁对林可霉素生物利用度的影响

通过8名健康志愿者服药后的对照实验,用微生物法检测血药浓度,按一室模型配置求算药物动力学参数,探讨西咪替丁对林可霉素体内过程的影响。结果表明,西咪替丁不能改变林可霉素的吸收速率(Ka)和消除速率(Ke),但可通过增加其吸收程度或改变其分布容积,使林可霉素的血药浓度和生物利用度分别增加约19％和27％。     

Comparative studies of chemotherapy of human tumor cells in vitro by tritiated thymidine uptake inhibition and soft agar clonogenic assay

A rapid nonsterile short-term assay has been investigated in which percent inhibition of incorporation of the DNA precursor (3H)-thymidine is measured following exposure of tumor cells to the test drugs. To evaluate the usefulness of the short-term assay in providing a rapid reliable assessment of chemotherapeutic response, the short-term assay was compared with the soft agar clonogenic assay. Sensitivity to five anticancer drugs was compared using three human tumor cell lines (epidermoid carcinoma of the oral cavity, pancreatic carcinoma, and bladder carcinoma). The short-term assay produced results that were similar to results of the clonogenic assay in two of the three tumors tested, for three drugs (cis-platin, doxorubicin, and BCNU), but did not detect responses to two antimetabolites (5-FU and MTX) in any tumor. Further studies of this short-term assay should focus on alkylating agents and other nonantimetabolites.     

特异性荧光偏振免疫法监测521例肾移植后环孢素A全血浓度3275次

目的通过监测肾移植后病人环孢素A(CsA)全血浓度 ,提出CsA在三联免疫抑制用药方案中的理想治疗窗。方法用特异性荧光偏振免疫法测定CsA全血浓度 ,对521例病人监测3275次 ,按术后时间及临床表现分组比较。结果肾移植后<1 ,、1～3、3～6、6～12个月、1～2和>2年的CsA全血谷浓度的理想治疗窗应分别为250～450、200～400、150～300、100～250、100～200和100～180μg/L。结论CsA全血浓度在上述范围内 ,中毒反应和排异反应明显减少     

Cholera Toxin B-Mediated Targeting of Lipid Vesicles Containing Ganglioside GM1 to Mucosal Epithelial Cells

Purpose. To determine whether the non-toxic pentameric B subunit of Cholera toxin (CTB) binding to ganglioside GM1 on both the lipid vesicles and epithelial cells may provide a means to target lipid vesicles to mucosal cells expressing surface GM1. Methods. Sonicated lipid vesicles containing ganglioside GM1 were prepared. Inter-vesicle cross-linking due to pentameric CTB binding to these GM1 vesicles was determined with a sub-micron particle analyzer. Association of CTB to GM1 vesicles was analyzed with continuous sucrose gradient centrifugation. CTB-mediated binding of GM1 vesicles to human mucosal epithelial cells (Caco-2 and HT-29), mucous membranes of mouse trachea, and nasal tissues were detected with fluorescent labeled vesicles. Results. An increase in lipid particle size due to binding of CTB to lipid vesicles and inter-vesicles cross-linking was detected. At a 30-to-1 mole ratio of membrane-bound GMl-to-CTB, optimum increase in GM1 vesicle aggregation, was detected. Under such conditions, all the added CTB molecules were associated with GM1 vesicles. Time course analysis showed that inter-vesicles cross linking by CTB was detectable within 10 min. and reached a maximum value at 60 min. CTB associated GM1-vesicles bind to mucosal epithelial cells HT-29 and Caco-2 with similar affinity [K_d = 7.8 × 10^–4 M lipid (Caco-2) and 7.6 × 10^–4 M lipid (HT-29)]. GM1 mediated binding specificity was demonstrated by blocking with anti-GMl antibody and the insignificant degree of CTB-associated GM1 vesicle binding to GM1 deficient C6 cells. Conclusions. The CTB-mediated GM1 binding to multiple membrane surfaces provides selective localization of GM1 vesicles to GM1 expressing mucosal cells and tissues. The strategy may be useful in localizing drugs and proteins to gut and respiratory tract mucosa.     

重视药物利用评价研究,开展药物利用评价活动

药物利用评价是当前医院合理用药的深入发展的重要体现,也是临床药学的重要工作之一。本文论述了药物利用评价的目的、意义、方法和进展,以及药物利用评价在医院药房中的应用,以期引起有关人员的重视。     

Capillary gas chromatographic assay of camphor and m-cresol in dermatological creams

Camphor and m-cresol mixtures are used in antiseptic and anti-itching creams. No compendial method exists for these preparations. This paper reports a capillary gas chromatographic method using FID detection with 2,6-di-tert-butyl-4-methylphenol as internal standard on a 30 m×0.32 mm Supelcowax®-10 column (0.25 μm film) with helium as carrier gas. Ramped temperature programming was applied. The method allows simultaneous quantitation of camphor and m-cresol in the presence of o- and p-cresols, calamine and zinc oxide. Overall percent recoveries (±SD, n=9) of camphor, o-, p- and m-cresol from spiked placebo creams, at a labeled amount of 10 (w/w)% were 96.9±0.6, 98.2±0.6, 99.2±0.5 and 101.0±0.9%, respectively, and at a labeled amount of 1% were 96.7±0.6, 97.8±0.9, 97.8±0.6, and 100.3±1.0%, respectively. The recovery studies were carried out at ±30% of the labeled amounts. Linear peak area or height ratios were obtained (r>0.999) for camphor, o-, p- and m-cresol covering a concentration range of 10–200% of the labeled amount. Linearity (r>0.999) was also obtained for m-cresol when the relative concentration of o- and p-cresol was varied from 5 to 100% of the m-cresol concentration. The resolution between the ‘critical pair’ of p- and m-cresol was ≥1.1. The limit of quantitation was 23 pg for m-cresol and 9.3 pg for camphor using an injection split of 1:50. The repeatability (%RSD) for all compounds were <2% for peak area and <1.4% for peak height ratios. System suitability and robustness of the method were established. The method was successively applied to the assay of available commercial products and allows assay of camphor and the three cresol isomers.     

Drug related hospital admissions

Summary As part of a high-intensity monitoring study of drug events as the cause of admission to departments of internal medicine, the effect of an educational intervention programme was studied. Two departments were included, one specialising in geriatrics and one that received patients by non-selected referral. The series consisted of 607 consecutive admissions studied before and 703 after the intervention. The drug events considered were adverse drug reactions and dose-related therapeutic failures, mainly due to non-compliance.A modest, statistically non-significant decrease in drug related hospital admissions (DRH) was seen, from 14% before to 13% after the intervention period. However, DRHs classified as definitely avoidable showed the significant decrease of 83%.There was no apparent relationship between the topics selected for the intervention programme and changes in the pattern of DRHs. No relationship between alterations in sales data and hospital admissions caused by a given drug could be demonstrated. A blinded external evaluation of case abstracts did not disclose any significant shift in the investigators' assessments.The intervention may have had an non-specific effect on avoidable DRHs.     

A new and highly sensitive method for measuring 3-methoxytyramine using HPLC with electrochemical detection. Studies with drugs which alter dopamine metabolism in the brain

3-Methoxytyramine (3-MT) is a minor metabolite of dopamine which is suggested to reflect the turnover and utilization of dopamine. A novel, isocratic HPLC method has been developed which can be used to analyse 3-MT in homogenates of rat brain without the need for additional purification procedures. Furthermore, the coulometric electrochemical detection system is sensitive enough to measure 3 pg of 3-MT (equivalent to 0.6 ng/g tissue wet weight). 3-Methoxytyramine was measured in the striatum and n. accumbens after decapitation and rapid freezing, using 3-methoxy-4-hydroxybenzylamine as the internal standard. The effects of dopaminergic and other drugs on this metabolite were examined using this method. -Methyl-p-tyrosine (200 mg/kg i.v.) produced parallel linear decreases in dopamine and 3-MT in naive rats, but not those pretreated with tranylcypromine (5 mg/kg i.p.). Methamphetamine (0.3–10 mg/kg i.p.) and amphetamine (0.3–10 mg/kg i.p.) both dose-dependently increased 3-MT in naive and tranylcypromine-pretreated rats. In naive animals, 3-MT was not altered by intraperitoneal injection of the dopamine reuptake inhibitors, bupropion (10 mg/kg) and nomifensine (10 mg/kg) or by sibutramine HCl (3 mg/kg), amitriptyline (10 mg/kg), desipramine (10 mg/kg) and zimeldine (10 mg/kg). 3-Methoxy-tyramine was decreased by apomorphine (5 mg/kg i.p.) and also by large doses of the selective D₂ antagonist, BRL 34778 (5 mg/kg i.p.) or -DOPA (50 mg/kg i.p.). The selective D₁ antagonist, SCH 23390 (0.1 or 5 mg/kg i.p.) was without effect. In tranylcypromine-pretreated rats, 3-MT was dose-dependently reduced and increased by apomorphine (0.01–5 mg/kg i.p.) and BRL 34778 (0.1–5 mg/kg i.p.), respectively. The drug SCH 23390 (0.1–5 mg/kg i.p.) produced much smaller increases in 3-MT which were probably mediated through the striatonigral pathway. Overall, the data suggest that measurement of 3-MT, after inhibition of monoamine oxidase, is a useful index of the release and utilization of dopamine. However, after substantial and prolonged depletion of dopamine, levels of 3-MT in naive animals are a better index. Also, the formation of 3-MT in naive rats provides a sensitive method for distinguishing between dopamine releasing agents and reuptake inhibitors.