复方氯唑沙宗的药理和临床应用

复方氯唑沙宗片是由氯唑沙宗和对乙酰氨基酚组成的中枢骨骼肌松弛剂,已被列入美国21版药典。氯唑沙宗和对乙酰氨基酚有镇痛协同作用。临床验证表明:复方氯唑沙宗片疗效优于氯唑沙宗片。 1 药理作用研究 1.1 肌肉松弛作用:以小鼠攀网法肌松作用比较,复方氯唑沙宗片与氯唑沙宗片都具有肌肉松弛作用,且呈剂量依赖性,ED_(50)复方氯唑沙宗片为195.72±37.83mg/kg,氯唑沙宗片为187.50±34.40mg/kg,若将复方制剂的ED_(50)以其中所含氯唑沙宗的剂量计算,其ED_(50)仅88.97mg/kg,低于单方应用氯唑沙宗。     

复方氯唑沙宗胶囊人体生物等效性研究

目的:比较复方氯唑沙宗胶囊与片剂的生物等效性。方法:20名男性健康志愿者,双交叉于试验当日晨空腹一次口服试验制剂复方氯唑沙宗胶囊、参比制剂复方氯唑沙宗片各2粒/片,于给药前及给药后0.25、0.5、0.75、1.0、1.5、2.0、2.5、3.0、4.0、5.0、6.0、8.0、10.0、12.01、5.0 h取肘静脉血,剂间间隔为1周。高效液相色谱法同时测定复方氯唑沙宗中氯唑沙宗和对乙酰氨基酚的血药浓度。血药浓度-时间数据经DAS 2.0处理,对主要药动学参数进行方差分析、双单侧t检验和(1-2α)置信区间分析,并计算相对生物利用度评价两种制剂的生物等效性。结果:复方氯唑沙宗胶囊中的对乙酰氨基酚和氯唑沙宗与片剂中同种成分的相对生物利用度分别为(109.1±30.9)%和(114.0±50.5)%。结论:复方氯唑沙宗胶囊与片剂为生物等效制剂。     

HPLC 法测定氯唑沙宗胶囊含量

用ＯＤＳ柱、甲醇∶水（４∶６）为流动相，以非那西丁为内标，测定氯唑沙宗胶囊中氯唑沙宗和扑热息痛的含量．结果为氯唑沙宗和扑热息痛线性范围分别是０．１２～０．６０ｍｇ，０．１０～０．５０ｍｇ；回收率分别为９７．１％，９６．４％，标准差为１．３％，１．２％．     

氯唑沙宗的合成

氯唑沙宗(chlorzoxazone,1),化学名5-氯-2(3H)-苯并(口恶)唑酮,为一强效肌肉松弛药,工业上是以邻氨基对氯苯酚(2)与脲环合而成,可使用60%硫酸的熔融法(本刊1987,18:49)和使用乙酸丁酯的溶剂法(本刊1988,     

系数倍率法测定复方氯唑沙宗片的含量

不经任何分离,应用系数倍率法可同时测定复方氯唑沙宗片中两种组分的含量,方法可靠易行。     

氯唑沙宗片治疗肌肉痉挛疼痛的临床观察

氯唑沙宗片治疗60例各种软组织损伤患者,总有效率为93.5％,并以安定为对照组,观察服药前后不同时间,症状减轻程度和活动改善情况,结果显示氯唑沙宗疗效,较安定为好,且不良反应小。     

HPLC法测定氯唑沙宗片含量

本文采用HPLC测定氯唑沙宗片中氯唑沙宗含量。以甲醇:水(50:50)为流动相,非那西丁为内标,在280nm处检测。其平均回收率为99.93％,RSD=0.55％,方法简便、准确。     

复方氯唑沙宗胶囊人体药物动力学研究

目的建立同时测定复方氯唑沙宗胶囊中两种成分血药浓度的方法,并进行其在健康人体药物动力学研究。方法20名男性健康志愿者单剂量口服复方氯唑沙宗胶囊2粒,高效液相色谱法同时测定复方氯唑沙宗中氯唑沙宗和对乙酰氨基酚的血药浓度。结果和结论复方氯唑沙宗胶囊中的氯唑沙宗和对乙酰氨基酚主要药物动力学参数分别为:t1/21.629±2.218 h和3.82±1.222 h;Tm ax1.333±0.636 h和0.958±0.724 h;Cm ax4.995±2.11 mg.L-1和1.85±0.409 mg.L-1;AUC0~15 h12.16±4.192 mg.h-1.L-1和8.661±2.844 mg.h-1.L-1;AUC0~∞12.34±4.328和9.927±3.644 mg.h-1.L-1。     

氯唑沙宗及其代谢物的HPLC测定方法和药代动力学研究

目的旨在建立氯唑沙宗及其代谢物的方法。应用高效液相色谱法,内标物为5-fluorobenzoxazolone,经乙酸乙酯提取,紫外检测波长为287nm。结果表明,6-羟氯唑沙宗、内标物及氯唑沙宗的保留时间分别为6.12,10.47和18.65min。6-羟氯唑沙宗及氯唑沙宗在0.5～20μg·ml^-1血浆浓度范围内线性关系良好,回收率均在82.80%～100.76%之间,当日及日间相对标准差分别小于8%和11%。两药的最低检测浓度分别为0.2和0.5μg·ml^-1。多种常用药物对样品的色谱峰无干扰。曾对8名健康受试者单次口服氯唑沙宗400mg的药代动力学进行了观察。提示此方法可用于氯唑沙宗的体内氧化代谢研究。     

紫外分光光度法测定复方氯唑沙宗片中扑热息痛的含量

本文采用紫外分光光度法测定复方氯唑沙宗片中扑热息病的含量,较现行标准的方法为简单,结果较为满意。     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.     

The debate on DDT

The paper reviews the early toxicologic and pharmacologic studies carried out by the author and his associates from 1943 to 1947, which were largely responsible for launching DDT as an agent for the control of typhus, malaria, yellow fever, and related vector-borne diseases. After reviewing recent studies conducted at the University of Miami, which dealt with organochlorine pesticides in human tissues, the tumorigenicity of aldrin, dieldrin and endrin (rat), six-generation mouse and three-generation dog reproduction studies, synergism of DDT and aldrin (dog), and the fate of DDT and aldrin during a period of severe starvation (rat), it is pointed out that it is primarily the overuse and misuse of DDT in pest control that have caused the pollution in our ecology. It is emphasized that the requirements for pest control differ the world over and that it must therefore be left to the national regulatory agencies to legislate the safe use of DDT and related pesticides. It is recommended that future human and animal studies with DDT and its derivatives give consideration to: (a) the balance and metabolism of the various hormones, (b) reproduction (estrus, libido, mammary development, milk production, (c) hepatic microsomal enzyme activities, (d) cancer prevention and cancer production, (e) excessive body weight changes induced by disease, unbalanced diet or starvation, and (f) the effects of DDT and its derivatives when absorbed in combination with other related and even unrelated compounds.Presented at the joint meeting of the Scandinavian and German Pharmacological Societies, Copenhagen, Denmark, July 20–23, 1971.     

A review of poisonous plants that cause reproductive failure and malformations in the ruminants of Brazil

The objective of this review is to provide a report on toxic plants causing reproductive problems in ruminants in Brazil. Aspidosperma pyrifolium causes abortion or stillbirth in goats, as well as most likely in sheep and cattle, in the semiarid regions of Northeastern Brazil. Intoxications by Ateleia glazioveana, Tetrapterys acutifolia and T. multiglandulosa result in abortion and neonatal mortality in cattle and sheep, and the same signs have been experimentally observed in goats. These three plants can also cause cardiac fibrosis and a nervous disease with spongiosis of the central nervous system. Other plants known to cause abortion include Enterolobium contortisiliquum, E. gummiferum, Stryphnodendron coriaceum, S. obovatum and S. fissuratum. These plants can also cause digestive signs and photosensitization. Abortions have been reported in animals intoxicated by nitrates and nitrites as well. Infertility, abortions and the birth of weak offspring have been reported in animals intoxicated by plants containing swainsonine, including Ipomoea spp., Turbina cordata and Sida carpinifolia. Trifolium subterraneum causes estrogenism in cattle. Mimosa tenuiflora and, most likely, M. ophthalmocentra cause malformations and embryonic mortality in goats, sheep and cattle in the semiarid regions of Northeastern Brazil.     

Gender-related symptoms and correlates of alcohol dependence among men and women with a lifetime diagnosis of alcohol use disorders

This study explored gender-related symptoms and correlates of alcohol dependence in a crosssectional study of 150 men and 150 women with a lifetime diagnosis of alcohol use disorders (AUD). Participants were recruited in equal numbers from treatment settings, correctional centres and the general community. Standardized measures were used to determine participants' use of substances, history of psychiatric disorders and psychosocial stress, their sensation seeking and family history of substance use and mental health disorders. Multivariate analyses were used to detect patterns of variables associated with gender and the lifetime severity of AUD. Men had a longer history of severe AUD than women. Women had similar levels of alcohol dependence and medical and psychological sequelae as men, despite 6 fewer years of AUD. More women than men had a history of severe psychosocial stress, severe dependence on other substances and antecedent mental health problems, especially mood and anxiety disorders. There were differences in family history of alcohol-related problems approximating same-gender aggregation. The severity of a lifetime AUD was predicted by its earlier age at onset and the occurrence of other disorders, especially anxiety, among both men and women. The limitations in the generalizability of these findings due to sample idiosyncrasies are discussed.     

药师在医院核辐射和放射事故应急准备与响应工作中的作用

目的:探讨药师在医院核辐射和放射事故应急准备与响应工作中的作用,以期为相关应急工作的开展提供参考。方法:根据国内、外相关参考资料,结合我院的实际工作情况,从药品储备、药品使用和放射病诊治中的临床药学3个方面对药师在医院核辐射和放射事故应急准备与响应工作中的作用进行分析。结果与结论:药品储备方面,药师可通过制定核辐射和放射事故应急药品目录、紧急状况下配制急需制剂和妥善贮存药品等途径发挥作用;药品使用方面,药师可通过在发生核辐射和放射事故时承担药品的发放与管理、对伤员进行用药指导等途径发挥作用;放射病诊治中的临床药学方面,临床药师应尽量选用同类药品中对肝、肺、肾等具有保护作用且毒副作用最小的品种,且以便于使用或局部给药为佳,同时密切关注治疗效果及不良反应。药师在医院核辐射和放射事故应急准备与响应工作中能够发挥重要作用。     

Towards standards for data exchange and integration and their impact on a public database such as CEBS (Chemical Effects in Biological Systems)

Integration, re-use and meta-analysis of high content study data, typical of DNA microarray studies, can increase its scientific utility. Access to study data and design parameters would enhance the mining of data integrated across studies. However, without standards for which data to include in exchange, and common exchange formats, publication of high content data is time-consuming and often prohibitive. The MGED Society (www.mged.org) was formed in response to the widespread publication of microarray data, and the recognition of the utility of data re-use for meta-analysis. The NIEHS has developed the Chemical Effects in Biological Systems (CEBS) database, which can manage and integrate study data and design from biological and biomedical studies. As community standards are developed for study data and metadata it will become increasingly straightforward to publish high content data in CEBS, where they will be available for meta-analysis. Different exchange formats for study data are being developed: Standard for Exchange of Nonclinical Data (SEND; www.cdisc.org); Tox-ML (www.Leadscope.com) and Simple Investigation Formatted Text (SIFT) from the NIEHS. Data integration can be done at the level of conclusions about responsive genes and phenotypes, and this workflow is supported by CEBS. CEBS also integrates raw and preprocessed data within a given platform. The utility and a method for integrating data within and across DNA microarray studies is shown in an example analysis using DrugMatrix data deposited in CEBS by Iconix Pharmaceuticals.     

5种不同细胞对柯萨奇病毒A组16型和肠道病毒71型的敏感性研究

 目的   评价肠道病毒研究中常用的5种细胞对柯萨奇病毒A组16型（coxsackievirus A16,CA16）和肠道病毒71型（enterovirus 71,EV71）的敏感性,为分离和培养CA16和EV71提供实验室依据。方法  用分离的各15株CA16和EV71分别感染RD、Vero、KMB17、Hep2和L20B细胞,每天观察细胞病变情况,按Karber法计算病毒感染性滴度。采用不同的统计学方法（包括方差分析和卡方检验）比较5种细胞对CA16和EV71的敏感性差异。 结果   5种细胞的CA16和EV71病毒感染性滴度间的差异具有统计学意义（CA16：F＝18.481,P＝0.000;EV71：χ²＝63.106,P＝0.000）。在5种细胞中,RD细胞对2种病毒的敏感性最高,CA16和EV71的病毒感染性滴度分别可达7.8和8.2 lgCCID₅₀/ml,且均于接种细胞后48 h达增殖高峰,第4天进入增殖平台期;2种病毒在Hep2和L20B细胞中的病毒感染性滴度均较低,CA16分别为5.2和4.2 lgCCID₅₀/ml,EV71分别为4.9和4.0 lgCCID₅₀/ml,且2种病毒在接种后第6~7天才达增殖高峰,但仅L20B细胞中的2种病毒于接种后第7天进入增殖平台期;CA16在Vero和KMB17细胞中的病毒感染性滴度分别为6.9和7.3 lgCCID₅₀/ml,EV71分别为7.1和6.8 lgCCID50/ml,2种病毒均在接种Vero和KMB17细胞后第3天达到增殖高峰,第5天进入增殖平台期。 结论   RD细胞对CA16和EV71的敏感性最好,其次是Vero和KMB17细胞,而Hep2和L20B细胞并非是分离和培养这2种病毒的理想细胞。     

Structural elucidation of in vitro and in vivo metabolites of cryptotanshinone by HPLC-DAD-ESI-MS(n)

The structural elucidation of the in vivo and in vitro metabolites of cryptotanshinone which was the major active component isolated from rhizome of Salvia miltiorrhiza Bunge and possessed significant antibacterial, anti-dermatophytic, antioxidant, anti-inflammatory and anticancer activities was described. Nineteen phase I metabolites and six phase II metabolites of cryptotanshinone were elucidated and identified by a sensitive LC-DAD-ESI-MS(n) method, and their molecular structures were proposed on the basis of the characteristics of their precursor ions, product ions, chromatographic retention time and ultraviolet spectra. The in vivo and in vitro phase I metabolites were mainly biotransformed by four main routes, which were dehydrogenation, hydroxylation, furan ring cleavage and oxidation metabolism, and among these phase I reactions, dehydrogenation was the predominant metabolic pathway. Six in vivo phase II metabolites were identified as the glucuronided and the sulfated conjugates which showed a neutral loss of 176 and 80 Da, respectively. The biotransformation pathways of cryptotanshinone were proposed on the basis of this research.     

Comparison of effects of dual transporter inhibitors on monoamine transporters and extracellular levels in rats

Compounds that block both serotonin (5-HT) and norepinephrine (NE) transporters have been proposed to have improved antidepressant efficacy. We compared the ability of four dual transporter inhibitors-chlorimipramine, duloxetine, milnacipran and venlafaxine-to block monoamine transporters in vitro and in vivo and increase extracellular monoamines in rat brain. Inhibition of radioligand binding to clonal human monoamine transporters in vitro and in vivo in rats was determined. Extracellular concentrations of 5-HT and NE in rat prefrontal cortex (PFC) were quantified using the microdialysis technique. All compounds blocked binding to human 5-HT and NE transporters, although chlorimipramine and venlafaxine had markedly greater affinity for 5-HT than NE transporters. In vivo, chlorimipramine and duloxetine potently blocked both transporters, milnacipran blocked both with lower potency and venlafaxine only blocked the 5-HT transporter. Chlorimipramine and duloxetine increased robustly and approximately equally monoamine extracellular concentrations. Milnacipran produced only small increases in NE, whereas venlafaxine increased 5-HT markedly at the lower doses and both monoamines at high doses. Thus, the dual transporter inhibitors blocked 5-HT and NE transporters in vitro and in vivo with varying potency. Chlorimipramine, duloxetine, and high dose venlafaxine acted as dual transporter inhibitors in rat PFC and increased extracellular concentrations of the monoamines, indicating functional dual transporter inhibition.     

Có vay có tra (What goes around comes around): culture, risk and vulnerability to blood-borne viruses among ethnic Vietnamese injecting drug users

Introduction and Aims . Ethnic and cultural differences in vulnerability to drug‐related harms have received little attention in Australia. The current study aimed to explore the influence of cultural beliefs and practices on vulnerability to blood‐borne viral infections (BBVIs) among ethnic Vietnamese IDUs and to identify barriers to this group accessing health and preventive programmes. Design and Methods . Observational fieldwork and in‐depth interviews (n = 58) were conducted in South Western Sydney. Participants were recruited using a mix of snowball and theoretical sampling strategies. Open coding was used to inductively classify data into themes and data examined for regularities and variations in relationships between and within themes. Results . Participants embraced pluralistic approaches to prevention, diagnosis and treatment, relying on co‐existing layers of beliefs and utilising both traditional and western remedies. Four main cultural characteristics influenced vulnerability to BBVIs: trust and obligation, stoicism, the importance of ‘face’ and beliefs in fate. Other factors influencing injecting risk included low levels of knowledge, being in a state of withdrawal, availability of sterile injecting equipment and environmental constraints. Barriers to accessing services included stigma and discrimination, concerns in relation to confidentiality, long waiting times, resistance to pharmacotherapy treatment and language and financial barriers. Discussion and Conclusions . Results indicate a need for interventions based on culturally specific meanings and contexts of health, illness and risk. By understanding how culture impacts risk and protective behaviours among ethnic Vietnamese IDUs, clinicians and other service providers will be better equipped to meet the needs of this vulnerable group.