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.     

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.     

夏天无总生物碱对鼠血管性痴呆防治作用的研究

目的:考察夏天无总生物碱(TACDR)对鼠血管性痴呆(vascular dementia,VD)的防治作用及其机制。方法:采用反复脑缺血再灌注法制备小鼠VD模型,以跳台实验检测行为学;将大鼠反复夹闭双侧颈总动脉(CCA)结合腹腔注射硝普钠降低血压的方法制备大鼠VD模型;以Y型电迷宫检测大鼠行为学;并检测大鼠大脑皮层总抗氧化能力(T-AOC)及AChE,SOD,MD的含量。结果:TACDR能明显改善VD大、小鼠模型的学习、记忆能力,有效地降低模型大鼠大脑皮层AchE的含量,提高大脑皮层T-AOC,升高SOD的活力,降低MDA的含量。结论:TACDR对鼠VD有一定的防治作用,其作用机制与提高AChE的含量,减轻自由基的损伤有关。     

Addiction: the clinical interface

This review gives an overview of what we see as the key issues in the human pharmacology of drugs of addiction. We review evidence of efficacy and mechanisms by which treatments act and point out areas where further work is needed. The role of agonist, partial agonist and antagonist treatments for opioid addiction is detailed and current issues relating to the mechanisms of actions at the receptor level and how to improve on compliance are discussed. The role of the brain dopamine and GABA-A systems in drug dependence is considered in relation to the growing pharmacology of these receptor systems, and the current status of novel preclinical targets reviewed. In addition, the different roles of dynamic and kinetic factors in both addiction and its treatment are discussed in relation to the underlying neuropharmacology of the disorders as defined from human and preclinical studies. Finally, some pointers to future research and especially to drug development by pharma are elaborated.     

广东梅县城区体检人群血尿酸水平的调查研究

目的了解梅县城区人群的血尿酸水平和高尿酸血症（hyperuricemia,HUA）的患病率。方法对8532名行健康体检者的血尿酸及血清肌酐、血尿素氮、总胆固醇、甘油三酯、血糖和血压的测定结果进行统计分析。结果受检者血尿酸水平为（328±90）μmol／L,男性为（348±83）μmol／L、女性为（265±85）μmol／L,其中HUA的患病率：男12．66％,女8．12％,男女合计10．68％。HUA的患病率随年龄的增长而升高,并有年轻化趋势。HUA组血清肌酐、尿素氮、总胆固醇、甘油三酯、血糖、血压的异常率均显著高于血尿酸正常组（P〈0．05）。结论梅县城区人群血尿酸水平和HUA患病率与全国平均水平相近;HUA患病率随年龄的增长而升高,HUA患者容易伴发高脂血症、高血糖、高血压和肾功能损害。     

Acute and sublethal effects of two insecticides on earthworms (Lumbricus terrestris L.) under laboratory conditions

Earthworms (Lumbricus terrestris L.) were exposed to commercial formulations of endosulfan and aldicarb for 2, 7, and 15 days, and the LC(10), LC(25), and LC(50) were determined. Worms were then exposed to LC(10), LC(25), and LC(50) concentrations of endosulfan and LC(10) and LC(25) concentrations of aldicarb. The growth rate and total protein content were determined and related to endosulfan and aldicarb residues in soil and earthworms. Aldicarb was more toxic than endosulfan under the experimental conditions. The residues of endosulfan and aldicarb caused a significant reduction in the growth rate and total protein content of earthworms. The residues of endosulfan and aldicarb were monitored in soil and earthworms after 2, 7, and 15 days of exposure. The residues remaining in the soil after the experiments ranged between 37.75% and 68.54% of the applied concentration for endosulfan and between 10.13% and 67.71% of the applied concentration for aldicarb. Small amounts of both insecticides were detected in worms, and accumulation was more important for endosulfan. This study proposes the use of growth rate and total protein content as biomarkers for contamination by endosulfan and aldicarb.     

克班宁血液和关节微透析探针体内外回收率研究

目的：考察克班宁血液和关节微透析探针的体内外回收率及其稳定性。方法：采用正微透析法和反微透析法,分别考察克班宁灌流速率、质量浓度对血液和关节探针体外回收率的影响,探讨正、反微透析法的回收率之间的关系;将血液和关节探针分别植入大鼠颈静脉和关节腔,考察探针在大鼠体内10 h反向回收率的稳定性。结果：克班宁血液和关节探针体外正向和反向微透析的回收率随着灌流速率（1.0,1.5,2.0,2.5,3.0 μL·min^-1）的增大而降低;与克班宁质量浓度（4,8,16,40 μg·mL^-1）无关,正向回收率与反向回收率基本一致,说明可以用反微透析法的回收率代替正微透析法的回收率对药物实际浓度进行校正;克班宁血液和关节探针在大鼠体内10 h反向回收率保持相对稳定,血液和关节探针体内反向回收率分别为（65.57±1.11）%和（32.7±0.94）%。结论：建立的克班宁血液和关节微透析方法可用于克班宁大鼠血液和关节药动学研究。     

Molecular handling of cadmium in transporting epithelia

Cadmium (Cd) is an industrial and environmental pollutant that affects adversely a number of organs in humans and other mammals, including the kidneys, liver, lungs, pancreas, testis, and placenta. The liver and kidneys, which are the primary organs involved in the elimination of systemic Cd, are especially sensitive to the toxic effects of Cd. Because Cd ions possess a high affinity for sulfhydryl groups and thiolate anions, the cellular and molecular mechanisms involved in the handling and toxicity of Cd in target organs can be defined largely by the molecular interactions that occur between Cd ions and various sulfhydryl-containing molecules that are present in both the intracellular and extracellular compartments. A great deal of scientific data have been collected over the years to better define the toxic effects of Cd in the primary target organs. Notwithstanding all of the new developments made and information gathered, it is surprising that very little is known about the cellular and molecular mechanisms involved in the uptake, retention, and elimination of Cd in target epithelial cells. Therefore, the primary purpose of this review is to summarize and put into perspective some of the more salient current findings, assertions, and hypotheses pertaining to the transport and handling of Cd in the epithelial cells of target organs. Particular attention has been placed on the molecular mechanisms involved in the absorption, retention, and secretion of Cd in small intestinal enterocytes, hepatocytes, and tubular epithelial cells lining both proximal and distal portions of the nephron. The purpose of this review is not only to provide a summary of published findings but also to provide speculations and testable hypotheses based on contemporary findings made in other areas of research, with the hope that they may promote and serve as the impetus for future investigations designed to define more precisely the cellular mechanisms involved in the transport and handling of Cd within the body.     

盐酸米托蒽醌脂质体的药效学及毒性研究

目的对盐酸米托蒽醌脂质体(Mit-lipo)与盐酸米托蒽醌普通制剂(Mit-inj)进行药效学及毒性比较研究。方法采用小鼠肝癌H22、小鼠前列腺癌RM-1移植肿瘤模型探讨Mit-lipo的抗肿瘤作用;犬急性毒性、大鼠和犬长期毒性研究比较Mit-lipo和Mit-inj毒性差异。结果 Mit-lipo 1、2、4和6 mg.kg-1各剂量对H22实体瘤的抑瘤率分别为75.1%、76.5%、90.1%和93.8%,也可剂量依赖性抑制小鼠前列腺癌RM-1肿瘤的生长,与等剂量的Mit-inj相比疗效明显增强。犬急性毒性结果表明Mit-lipo最大耐受剂量(MTD)为2.0 mg.kg-1,毒性表现为轻微至中度的皮肤毒性,给药4周后皮肤毒性逐渐减轻。大鼠长期毒性结果表明Mit-lipo可明显降低Mit-inj引起的骨髓毒性,并产生新的皮肤毒性反应。犬长期毒性结果表明Mit-lipo 0.1、0.3和0.45mg.kg-1组主要毒性反应为轻微至轻度的皮肤毒性反应,主要毒性靶器官为睾丸和皮肤,MTD为0.45 mg.kg-1,Mit-inj0.45 mg.kg-1可致WBC和PLT值降低和睾丸毒性病变。结论与普通制剂相比,米托蒽醌脂质体的体内抑瘤效果明显增强,且骨髓毒性明显降低。     

支链氨基酸代谢在糖肽类和环脂肽类抗生素产量提高与组分优化中的应用

摘要：糖肽类和环脂肽类抗生素具有很好的抗菌活性,临床上广泛用于治疗多重耐药菌导致的严重感染。大部分糖肽类和 环脂肽类抗生素均含有带支链结构的脂肪酸侧链,侧链结构差异是导致这两类抗生素发酵组分多样性的主要原因。支链脂肪酸 侧链的合成起始于支链氨基酸分解代谢,调控支链氨基酸代谢对于定向合成含有特定脂肪酸侧链的糖肽类和环脂肽类抗生素具 有重要作用。本文从糖肽类和环脂肽类抗生素中脂肪酸侧链的生源途径、外源添加支链氨基酸对糖肽类和环脂肽类抗生素产量 和组分的影响,内部改造支链氨基酸代谢途径对糖肽类和环脂肪肽类抗生素产量和组分的影响3方面进行了综述。     

Teaching ethics of psychopharmacology research in psychiatric residency training programs

Rationale American psychiatric residency training programs are now required to teach principles of research ethics. This task is especially pressing in light of evolving guidelines pertaining to human subjects, including psychiatric patients, especially when psychopharmacology is involved. Residents need to understand principles of research ethics and implications of roles of psychiatrists as investigators and clinicians. Objectives We consider major contemporary ethical issues in clinical psychiatric research, with an emphasis on psychopharmacology, and implications of addressing them within residency training programs. Methods We reviewed recent literature on ethical issues in clinical research and on medical education in bioethics. Results This report considers: (1) an overview of current training; (2) perceived needs and rationales for training in research ethics, (3) recommended educational content and methods; (4) issues that require further study (including demonstration of acquired knowledge, practice issues, and the treatment versus-investigation misconception); and (5) conclusions. Recommended components of residency training programs include basic ethical principles; scientific merit and research design; assessment of risks and benefits; selection and informed consent of patient-subjects; and integrity of the clinical investigator, including definition of roles, conflicts-of-interest, and accountability. Evaluation of educational effectiveness for both trainees and faculty is a recommended component of such programs. Conclusions We recommend that psychiatric training include education about ethical aspects of clinical research, with a particular emphasis on psychopharmacology. These activities can efficiently be incorporated into teaching of other aspects of bioethics, research methods, and psychopharmacology. Such education early in professional development should help to clarify roles of clinicians and investigators, improve the planning, conduct and reporting of research, and facilitate career development of much-needed clinical investigators in psychiatry.     

兰州市102家医疗机构麻醉、精神药品管理、使用中存在问题分析

目的:为医疗机构进一步规范管理麻醉、精神药品提供参考。方法:通过检查兰州市属3县5区102家医疗机构,就麻醉、精神药品在管理、使用中存在的问题,从卫生监管部门、医疗机构、执业医师、药学专业技术人员等层面进行分析,提出解决问题的建议。结果与结论:医疗机构对执业医师、药学专业技术人员培训、考核力度不够,相关人员对法规掌握、了解不够,专业知识陈旧,管理上宽严失度,临床用药观念保守,用药结构不合理。尤其是民营医疗机构、乡镇卫生院问题突出,存在较多的安全隐患。应针对上述问题采取相应措施,从源头抓起,才能使各级医疗机构麻醉、精神药品的使用、管理更加规范。     

Suffering,Choice, and Freedom

This article attempts to describe illness as a comprehensive individual experience quoting both sacred texts and writings of famous authors. Illness needs the concepts and the practices of soul, spirit, and meaning, which are the counterparts of the current medical notion of bodily and mental processes. In their absence, even the relationship from clinician and client transforms itself into a hopeless and compulsive interaction. Illness affects both feeling and thoughts in an unpredictable way and may allow an individual to rise through spiritual pathway it implies. The passage between pain and suffering toward the experience of freedom occurs by means of dark or even desperate moments, when active listening to the person in need and the operation of a Higher Power are necessary opportunities. Health professionals, nowadays in favor of medical technology and of the actions oriented to fighting the disease, may develop a therapeutic communication with their patients in order to help their understanding of the meaning that their illness has at the end for themselves.     

The concept of conditional pharmacology and toxicology

The concept of conditional pharmacology as initially elucidated by Dr Michael Whitehouse and his colleagues from their studies of drug-disease interactions has broad import in a rational drug discovery and development programme. The concept can be extended to toxicology and thus can be viewed as encompassing virtually all means and methods of discovering and enhancing the efficacy, while reducing the toxicity of drugs and biologics. The concept involves employing the physiological or metabolic activity, genetic and/or molecular structure of the host, of the disease process and/or of the parasite to activate and target the drug or biologic, as well as to regulate and delimit its activity. Thus, the concept not only applies to the treatment of inflammatory diseases, but also to the treatment of neoplastic and infectious diseases, to facilitating wound healing, and is in fact an underlying assumption, and expected consequence, of successful gene therapy. The concept applies to clinical studies as well, arguing for more pharmacokinetic and chrono-pharmacological studies in the early phases of clinical testing and the inclusion in later-stage clinical trials of more diverse populations, as regards age, gender and ethnicity, if the indication warrants. Facilitating and monitoring compliance, post-as well as pre-market approval, also are critical components of the fully implemented concept.     

纳米喜树碱的蛋白结合率及其在血清中的稳定性研究

目的:考察纳米喜树碱与不同种属蛋白结合情况及其在不同种属血清中的稳定性。方法:用高效液相色谱法测定纳米喜树碱在人白蛋白和牛白蛋白的磷酸盐溶液中的蛋白结合率,以及在小鼠、小牛、人血清和磷酸盐溶液中内酯环形式的稳定性。结果:纳米喜树碱在牛白蛋白和人白蛋白中的结合率分别为(38.0892±2.9034)%和(27.3305±4.2618)%,在小牛和人的血清中开环速度较在磷酸盐和小鼠血清中快。结论:蛋白和血清的种属差异是影响纳米喜树碱稳定性的关键因素。     

药品注册审批工作中专利相关问题探讨

目的:探讨如何正确处理药品注册审批工作中的专利相关问题。方法:分析我国药品注册审批工作中专利相关规定及其存在的问题,并参照美国、欧盟的相关规定进行比较与分析。结果与结论:药品注册审批与专利权保护是相对独立的法律关系,分别适用药品管理法和专利法;药品注册审批与专利侵权之间没有必然联系;专利纠纷应当按照专利法的相关规定解决,药品注册审批工作不应当涉及药品专利纠纷的解决。     

甲基黄酮醇胺盐对大鼠学习记忆的促进作用与其抗氧化作用的关系

目的研究甲基黄酮醇胺盐对大鼠学习记忆的影响，分析该药影响学习记忆与其影响脑内自由基反应的关系。方法ｉｐ甲基黄酮醇胺盐５，１０ｍｇ·ｋｇ－１共７ｄ后，采用Ｍｏｒ－ｒｉｓ水迷宫测试大鼠的学习记忆能力，同时测定训练ｄ５和休息３０ｄ后大鼠脑内过氧化脂质（ＬＰＯ）含量和超氧化歧化酶（ＳＯＤ）活性。结果甲基黄酮醇胺盐两种剂量均可提高大鼠获取空间定位信息能力和信息贮存能力并增强记忆保持和再现过程。用药大鼠脑内ＬＰＯ含量明显低于对照组，与其记忆成绩呈正相关性。而脑内ＳＯＤ活性则高于对照组，与其记忆成绩呈负相关性。结论甲基黄酮醇胺盐对大鼠的学习记忆机能具有促进作用，而它的抗氧化作用可能为其促进学习记忆的作用机制。     

雄激素、 雌激素受体在尿道下裂患儿阴茎皮肤中的表达

摘要： 目的 探讨雄激素受体 （AR） 及雌激素受体 （ER） 在尿道下裂患儿阴茎不同部位表皮及真皮中的分布特点。方法 收集 30 例尿道下裂患儿阴茎背侧皮肤 （背侧组）、 异位尿道口腹侧皮肤 （腹侧组） 及尿道板皮肤组织 （尿道板组）, 应用免疫组织化学检测各组中 AR 和 ER 在表皮和真皮成纤维细胞中的表达情况, Image Pro plus 6.0 分析 AR 和 ER 在不同部位的表皮和真皮中的光密度 （OD） 值。结果 各组 AR、 ER 主要表达于阴茎皮肤基底细胞及棘细胞的细胞核, 也表达于真皮成纤维细胞的细胞核。AR 在表皮中的表达, 尿道板组低于背侧组和腹侧组 （P＜0.05）; 各组 AR 在真皮成纤维细胞中的表达差异无统计学意义。ER 在表皮中的表达, 背侧组高于腹侧组和尿道板组 （P＜ 0.05）; ER 在真皮成纤维细胞中的表达, 背侧组、 腹侧组和尿道板组呈依次升高趋势 （P＜0.05）。结论 阴茎尿道板组织中 AR 表达数量减少在尿道下裂发生中起重要作用, 阴茎皮肤真皮成纤维细胞中 ER 表达的失衡可能参与了尿道下裂的发生。     

Harmane inhibits serotonergic dorsal raphe neurons in the rat

Rationale Harmane and norharmane (two beta-carbolines) are tobacco components or products. The effects of harmane and norharmane on serotonergic raphe neurons remain unknown. Harmane and norharmane are inhibitors of the monoamine oxidases A (MAO-A) and B (MAO-B), respectively. Objectives To study the effects of harmane, norharmane, befloxatone (MAOI-A), and selegiline (MAOI-B) on the firing of serotonergic neurons. To compare the effects of these compounds to those of nicotine (whose inhibitory action on serotonergic neurons has been previously described). The effects of cotinine, a metabolite of nicotine known to interact with serotonergic systems, are also tested. Methods In vivo electrophysiological recordings of serotonergic dorsal raphe neurons in the anaesthetized rat. Results Nicotine, harmane, and befloxatone inhibited serotonergic dorsal raphe neurons. The other compounds had no effects. The inhibitory effect of harmane (rapid and long-lasting inhibition) differed from that of nicotine (short and rapidly reversed inhibition) and from that of befloxatone (slow, progressive, and long-lasting inhibition). The inhibitory effects of harmane and befloxatone were reversed by the 5-HT1A antagonist WAY 100 635. Pretreatment of animals with p-chlorophenylalanine abolished the inhibitory effect of befloxatone, but not that of harmane. Conclusions Nicotine, harmane, and befloxatone inhibit the activity of raphe serotonergic neurons. Therefore, at least two tobacco compounds, nicotine and harmane, inhibit the activity of serotonergic neurons. The mechanism by which harmane inhibits serotonergic dorsal raphe neurons is likely unrelated to a MAO-A inhibitory effect.     

山葡萄素抗动脉粥样硬化分子机制研究

目的对从山葡萄籽来源的山葡萄素A和二脱氢山葡萄素A发挥抗动脉粥样硬化作用的分子机制进行深入的研究。方法采用体外培养的人脐静脉内皮细胞Hy926、鼠巨噬细胞RAM264.7和佛波酯(PMA)诱导的人单核细胞源性巨噬细胞THP-1,加入氧化低密度脂蛋白(ox-LDL)和脂多糖(LPS)损伤后,通过检测细胞活力(MTT法和LDH法)、活性氧、一氧化氮、丙二醛(MDA)和超氧化物歧化酶(SOD)的含量,以及细胞上清中细胞因子肿瘤坏死因子(TNF-α)和白介素1β(IL-1β)的分泌,单核细胞THP-1和内皮细胞Hy926的黏附作用,考察化合物的作用。结果化合物对ox-LDL导致的内皮细胞和巨噬细胞损伤有较明显的保护作用,并且抗氧化,减少氧、氮自由基产生,抑制LPS所致的巨噬细胞炎性因子释放,抑制单核细胞和内皮细胞黏附。结论山葡萄素A和二脱氢山葡萄素A对动脉粥样硬化(atherosclerosis,AS)发生早期事件的多个关键环节均有作用,提示其可能的动脉粥样硬化保护分子机制涉及多个靶点和通路的相互作用。