三氯乙醇对5－HT和ICS_（205－930）与［~3H］BRL_（46470

用放射配体受体结合分析法，观察了三氯乙醇（ＴＣＥｔ）对５－ＨＴ３受体激动剂５－ＨＴ和５－ＨＴ３受体拮抗剂ＩＣＳ２０５－９３０与［３Ｈ］ＢＲＬ１６１７０竞争大鼠脑皮质５－ＨＴ３受体能力的影响。结果证实，ＴＣＥｔ（４ｍｍｏｌ·Ｌ－１）能使５－ＨＴ竞争受体的浓度－反应曲线左移，半数抑制结合浓度降低（Ｐ＜０．０１），斜率无显著改变；而对ＩＣＳ２０５－９３Ｏ未见明显影响。表明ＴＣＥｔ能增强５－ＨＴ与５－ＨＴ３受体结合的能力，提示它可能通过这一机制促进５－ＨＴ３配体闸门离子通道开放而发挥作用。     

锰对大鼠仔代脑发育过程中单胺类神经递质的影响

采用荧光分光光度法测定孕期大鼠接触锰的Ｆ１代仔鼠新生儿期、１月龄期、２月龄期和３月龄期脑内单胺类神经递质的含量。结果为：１．新生儿期，染锰组脑内多巴胺（ＤＡ）含量显著增高（Ｐ＜０．０５）；去甲基肾上腺素（ＮＥ）和５－羟色胺（５－ＨＴ）无明显改变。２．１月龄期，染锰各组脑内ＮＥ含量明显高于对照组（Ｐ＜０．０１）；ＤＡ和５－ＨＴ含量与对照组相比无显著性差异。３．２月龄期，染锰各组的ＮＥ、ＤＡ和５－ＨＴ含量均比对照组低（Ｐ＜０．０５）。４．３月龄期，染锰各组的ＮＥ、ＤＡ和５－ＨＴ含量，与对照组间无显著性差异。结果提示，孕期接触锰对Ｆ１代仔鼠脑发育过程中单胺类递质的代谢，在其不同的发育时期产生了不同的影响。     

三氯乙醇对5—HT和ICS205—930与〔^3H〕BRL46470竞争大鼠脑皮…

用放射配体受体结合分析法，观察了三氯乙醇〔ＴＣＥｔ〕对５－ＨＴ３受体激动剂５－ＨＴ和５－ＨＴ３受体拮抗剂ＩＣＳ２０５－９３０与〔＾３Ｈ〕ＢＲＬ１６１７０竞争大鼠脑皮质５－ＨＴ３受体能力的影响。提示它可能通过这一机制促进５－ＨＴ３配体闸门离子通道开放而发挥作用。     

莲心碱对几种平滑肌作用的研究

莲心碱（Ｌｉｅ）抑制去氧肾上腺素（ＰＥ），５－羟色胺（５－ＨＴ），组胺（Ｈｉｓ）和高Ｋ＋引起的兔主动脉环收缩，对ＰＥ引起的收缩，其抑制作用更为明显；也抑制ＰＥ所致兔尿道平滑肌的收缩。在兔主动脉环和大鼠肛尾肌标本，Ｌｉｅ使甲氧胺（Ｍｅｔ）及ＰＥ的量效曲线平行右移，最大反应不压低，ＰＡ２值分别为６．８和６．６。Ｌｉｅ还明显抑制去甲肾上腺素（ＮＥ）所致的内钙释放，而对ＮＥ所致外钙内流影响较小。提示：Ｌｉｅ具有阻断肾上腺素α１受体和抑制细胞内钙释放作用。     

盐酸昂丹司琼的药效学观察

盐酸昂丹司琼（１）灌胃或静脉注射明显抑制顺铂诱发的犬呕吐反应，抑制５－ＨＴ诱发的麻醉大鼠的心率减慢。１腹腔注射显促进大鼠胃排空，作用优于盐酸甲氧氯普胺。     

肾性高血压的动态血压节律

应用２４小时无创性全自动动态血压记录仪观察了８７例受试对象，其中正常血压（ＮＴ）２０例；Ⅰ－Ⅱ期原发性高血压（ＥＨＴ）４４例；肾实质性高血压（ＲＨＴ）１２例；肾血管性高血压（ＲＶＨＴ）１１例。结果表明，各组受试者的随测血压均明显高于动态血压。ＮＴ及ＥＨＴ的动态血压呈夜晚下降、白昼上升节律，而无论是ＲＨＴ，还是ＲＶＨＴ，其昼夜节律均明显减弱，收缩压和舒张压的夜间下降值均明显低于正常人和原发性高血压患者，夜间下降率低于１０％者的比率却明显高于正常人和原发性高血压者。     

怀牛膝总皂甙对离体大鼠子宫的兴奋作用及机理研究

研究表明，怀牛膝总皂甙（ＡＢＳ０．１～０．４ｍｇ／ｍｌ）对离体大鼠子宫产生明显的浓度依赖性兴奋作用，５－ＨＴ（１０μｇ／ｍｌ）可明显增强ＡＢＳ的作用。ＡＢＳ和５－ＨＴ均使高Ｋ＋去极化后的高体大鼠子宫产生依细胞内Ｃａ２＋性和依细胞外Ｃａ２＋性收缩；氯两嗪（０．５μｇ／ｍｌ）或氟丙嗪（０．４μｇ／ｍｌ）和消炎痛（２０μｇ／ｍｌ）合用均明显拮抗ＡＢＳ的作用。     

氛氟拉明加强针刺镇痛时前脑啡肽原mRNA的表达

研究大鼠脑内前脑啡肽原ｍＲＮＡ的变化与５－ＨＴ的放剂芬氟拉明加强针刺镇痛的关系。用原位杂交组织化学观察ＰＰＥｍＲＮＡ的表达，脊髓背角，中缝大核，中缝背核，中央灰质，脚间核，视前外侧区，杏仁核和尾壳核内的ＰＰＥｍＲＮＡ的含量大量升高，而在隔外侧区，神前内侧区，正丘脑腹内侧核以及脊髓背角Ⅲ－Ⅳ层的ＰＰＥｍＲＮＡ的水平也有中等程度增高。但在丘脑却没有明显的变化。ＰＰＥｍＲＮＡ含量在与痛相关的区域里增高，     

氯酯醒对正常及电休克记忆障碍大鼠学习记忆的作用

氯酯醒１５０ｍｇ／ｋｇ，１０ｄ，ｐｏ可提高大鼠训练后第７天主动性回避反应的频数（穿梭箱法）及延长大鼠训练后３ｈ，２４ｈ在台上停留时间，即被动性回避反应的潜伏期（跳台法）；使大鼠额叶、纹状体、下丘脑、海马和脑干中５－ＨＴ含量明显增加；额叶和海马ＮＡ含量明显增加；下丘脑中ＤＡ含量明显增加．氯酯醒对电休克所致的大鼠记忆障碍也表现有明显地改善作用．     

吲哚美辛和乙胺嗪对缺氧大鼠肺血管阻力的影响

在慢性和急性缺氧条件下，Ｈｉｌｌｔｏｐ（ＨＴ）大鼠肺血管阻力（ＰＶＲ）升高程度显著比Ｗｉｓｔａｒ（ＷＴ）大鼠高。吲哚美辛可减少ＷＴ大鼠ＰＧＩ＿２产生，提高ＰＶＲ；对ＨＴ大鼠则减少ＴＸＡ＿２产生，降低ＰＶＲ。乙胺嗪和Ｕ－６０２５７Ｂ通过抑制５－脂加氧酶使白三烯（ＬＴｓ）产生减少，在缓解两种大鼠的缺氧性ＰＶＲ增高中起重要作用。     

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.     

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.     

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.     

四种药物在猪的药动学特征

为给疾病动物的药动学研究作准备,本文研究磺胺二甲嘧啶(SM_2)、异烟肼(ISZ)、磺溴酞(BSP)和酚磺酞(PSP)在猪(n=22,30～39 kg)的动态特征,结果表明,在猪体内,SM_2以中分布、低清除,INZ以高分布、高清除,BSP和PSP则以低分布、高清除为特征,药物的这些分布和消除特征直接影响药物在血中的浓度和在体内的滞留时间,而这些特征又是由机体的主要消除器官肝脏和肾脏对药物的消除能力以及药物与血浆蛋白的结合程度所决定。     

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.     

Effects of acute cannabis use on urinary neurotransmitter metabolites and cyclic nucleotides in man

The noradrenaline, dopamine and serotonin metabolites methoxy-hydroxyphenylglycol (MHPG), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA), as well as the cyclic nucleotides c-AMP and c-GMP were estimated in urine samples of five normal volunteers. Ten control samples and two samples after cannabis use were analyzed for each volunteer. Cannabis use caused significant decreases in MHPG and c-AMP, and increases in HVA, while 5-HIAA and c-GMP excretion remained unchanged. The results indicate that cannabis use interferes with catecholaminergic mechanisms in man, decreasing the noradrenaline and increasing dopamine turnover, probably through action on presynaptic receptors.     

Pregnancy-induced mobilization of copper and zinc bound to renal metallothionein in cadmium-loaded rats

Our investigations undertook to examine whether copper (Cu) and zinc (Zn) bound to renal metallothionein (MT) along with cadmium (Cd) in Cd-loaded rats can be mobilized during pregnancy and lactation. Rats of the Wistar strain were injected with Cd. Synthesis of MT containing Cd, Cu and Zn was induced in the kidneys. Concentrations of Cd and essential elements in blood plasma and organs (liver and kidneys) were compared among non-pregnant and pregnant, and Cd-loaded and non-loaded rats at middle and late gestational days and after delivery. Cu bound to renal MT was decreased with gestational age, while Zn was slightly increased. The results indicate that Cu was mobilized and utilized even when the metal was bound to MT in the kidneys of dams. On the other hand, Zn bound to renal MT in Cd-loaded rats was retained and not mobilized during pregnancy. The elution profile of renal MT on an SW column was changed from a typical renal to a mixed profile of renal and hepatic MTs as a result of decreased Cu content in MT. Plasma essential elements changed similarly with gestational age in both concentrations and distributions in non-loaded and Cd-loaded rats. These results indicate that the 3 metals bound to renal MT are dealt with differently during gestation and lactation, and Cu but not Zn is transferred to the fetus, independently of the Cd status of the dam.     

Do Spirituality and Religiosity Help in the Management of Cravings in Substance Abuse Treatment?

The purpose of this study was to examine the relationship of spirituality, religiosity and self-efficacy with drug and/or alcohol cravings. A cross-sectional survey was completed by 77 male participants at an Australian Salvation Army residential rehabilitation service in 2007. The survey included questions relating to the participants' drug and/or alcohol use and also measures for spirituality, religiosity, cravings, and self-efficacy. The sample included participants aged between 19 and 74 years, with more than 57% reporting a diagnosis for a mental disorder and 78% reporting polysubstance misuse with alcohol most frequently endorsed as the primary drug of concern (71%). Seventy-five percent of the clients reported that spirituality and religious faith were useful components of the treatment program. A multivariate multiple regression analysis identified that spirituality and self-efficacy have significant relationships with cravings. Self-efficacy mediated the relationship between spirituality and drug and/or alcohol cravings. The limitations of this study included its cross-sectional design and a sample that was drawn from a faith-based program. Future research would benefit from the longitudinal examination of the relationship between spirituality, self-efficacy, and cravings; the exploration of a broader range of client-specific and interpersonal variables; and the inclusion of a control group from a secular treatment facility.     

Biochemical and molecular characterisation of cubozoan protein toxins

Class Cubozoa includes several species of box jellyfish that are harmful to humans. The venoms of box jellyfish are stored and discharged by nematocysts and contain a variety of bioactive proteins that are cytolytic, cytotoxic, inflammatory or lethal. Although cubozoan venoms generally share similar biological activities, the diverse range and severity of effects caused by different species indicate that their venoms vary in protein composition, activity and potency. To date, few individual venom proteins have been thoroughly characterised, however, accumulating evidence suggests that cubozoan jellyfish produce at least one group of homologous bioactive proteins that are labile, basic, haemolytic and similar in molecular mass (42-46 kDa). The novel box jellyfish toxins are also potentially lethal and the cause of cutaneous pain, inflammation and necrosis, similar to that observed in envenomed humans. Secondary structure analysis and remote protein homology predictions suggest that the box jellyfish toxins may act as α-pore-forming toxins. However, more research is required to elucidate their structures and investigate their mechanism(s) of action. The biological, biochemical and molecular characteristics of cubozoan venoms and their bioactive protein components are reviewed, with particular focus on cubozoan cytolysins and the newly emerging family of box jellyfish toxins.