5-羟色胺转运体基因多态性与抗抑郁剂治疗广泛性焦虑障碍疗效的关联

目的:探索5-羟色胺转运体(5-hydroxytryptamine transporter,5-HTT)基因多态性与抗抑郁剂治疗广泛性焦虑障碍(generalized anxiety disorder,GAD)疗效的关联性。方法:188例符合DSM-IV广泛性焦虑障碍诊断标准的患者接受艾司西酞普兰（n=117）或者文拉法辛缓释剂（n=71）治疗8周,疗效判定以汉密尔顿焦虑量表（hamilton anxiety rating scale, HAMA）评分减分率及HAMA评分来评定。对所有患者及169例正常对照组接受5-HTT基因多态性检测。结果:5-HTT各基因型（SS、LS、LL）及等位基因（S、L）在GAD病例组和对照组的分布差异无统计学意义（P>0.05）。5-HTT各基因型患者基线时HAMA评分差异无统计学意义（F=0.052,P=0.949）。所有患者中SS、LS、LL基因型治疗后HAMA减分值差异无统计学意义（F=0.748,P=0.475）。艾司西酞普兰治疗组SS、LS、LL基因型治疗后HAMA减分值差异无统计学意义（F=0.210,P=0.811）。文拉法辛缓释剂治疗组SS、LS、LL基因型治疗后HAMA减分值差异有统计学意义（F=3.505,P=0.036）,LL基因型患者HAMA减分值显著高于SS和LS基因型。结论:5-HTT基因多态性与GAD发病的易感性之间可能无直接关系。5-HTT基因多态性和艾司西酞普兰的疗效不相关,但LL基因型的GAD患者接受文拉法辛缓释剂治疗的疗效可能优于SS和LS基因型。     

Isolation and tentative identification of lineatin,a pheromone from the frass ofTrypodendron lineatum (Coleoptera: Scolytidae)

An attractant compound was isolated from frass produced byTrypodendron lineatum female beetles boring in Douglas fir. The proposed structure is one of two isomeric tricyclic acetals, to which the trivial name lineatin is assigned.Research supported by: National Science Foundation (U.S.A.) Grant No. PCM 74-13643, National Research Council (Canada) Operating Grant No. A3881, Canada Department of Fisheries and Forestry Extramural Research Grant No. F-58, Canadian Forestry Service Science Subvention Grant, and the Council of Forest Industries of British Columbia.     

Complex Effects of Sertraline and Citalopram on In Vitro Murine Breast Cancer Proliferation and on In Vivo Progression and Anxiety Level

Some selective serotonin reuptake inhibitors (SSRIs), primarily sertraline, demonstrate anti-proliferative activity in malignant cell-lines and in xenografted mouse models of colorectal tumor. There is, however, a paucity of comparative studies on the anti-tumor effects of SSRIs. We compared the in vitro and in vivo effects of sertraline and citalopram on murine 4T1 breast cancer. Grafted mice were used to determine the rate of tumor growth and survival as well as the impact of stress and antidepressant treatment on tumor progression and mortality and on pro-inflammatory cytokines. Sertraline, in the micromolar range, but not citalopram, induced a significant in vitro concentration-dependent inhibition of murine 4T1 cell proliferation and splenocyte viability. In contrast, sertraline (10 mg/kg/d), enhanced in vivo tumor growth. Contrary to the study’s hypothesis, chronic mild stress did not modify tumor growth in grafted mice. The in vitro effects of sertraline on tumor growth seem to be the opposite of its in vivo effects. The impact of sertraline treatment on humans with breast cancer should be further investigated.     

珍贵三环核苷衍生物的理论计算与实验研究

N-4-desmethylwyosine (dYt), a derivative of rare tricyclic nucleosides is probably a new member of Y-nucleosides found in tRNA [1]. The structure of dYt has tricyclic ring with rigid conformation and high electron delocalization. Both the absorption and emission bands of dYt are well separated from normal bases, so it could probably be used as an effective natural fluorescent probe to study RNA structure and sequence[2].Fig.1 The secondary structure of yeast tRNAPbe anticodon loop and molecular structures ofguanosine and N-4-desmethylwyosine An ab initio study was performed to evaluate stability of three isomers of this compound. Ionization potential (IP) of dYt was calculated. It was found that the value was lower than that of guanosine and guanine. This shows that dYt loses electron more easily than guanine.In addition, the result has been verified by experimental studies performed by nanosecond laser photolysis.The reactions of dYt and a series of transient species such as reduction radicals eaq-, H· and oxidation radicals ·OH,SO4·-, CO3·- and N3· have been carried out by nanosecond pulse radiolysis. Rate constants of these reactions have been determined and related mechanisms were discussed.     

One-pot three-component synthesis of 2H-thiopyrano[2,3-b]quinoline-2,3-dicarboxylates from 2-mercaptoquinoline-3-carbaldehydes,dialkyl acetylenedicarboxylates and Ph3P

An extremely concise one-pot procedure toward the synthesis of 2H-Thiopyrano [2,3-b]quinoline-2,3-dicarboxylates whose applications as medicines is predictable has been established. This approach produces three fused rings evolving from the formation of four new carbon–carbon bonds and a stereogenic center in a one-pot protocol.     

Synthesis of Tricyclic Isoquinoline Derivatives via Palladium‐ Catalyzed Tandem Reactions of 2,7‐Alkadiynylic Carbonates with 2,3‐Allenyl Sulfamides

The palladium‐catalyzed tandem reactions of 2,7‐alkadiynylic carbonates with 2,3‐allenyl sulfamides for the syntheses of fused tricycles such as 1,3,6,7,8,9‐hexahydrofuro[3,4‐h]isoquinoline, 2,3,6,7,8,9‐hexahydro‐1H‐pyrrolo[3,4‐h]isoquinoline, and 2,3,4,7,8,9‐hexahydro‐1H‐cyclopenta[h]isoquinoline derivatives have been developed. A mechanism has been proposed based on the isolation of a by‐product.

     

Writing a wrong: Factors influencing the overprescription of antidepressants to youth.

Recently observed reductions in the use of antidepressant medication in youth come after a period that many have characterized as being marked by excessive reliance on such agents. The Food and Drug Administration advisory first issued in 2004 clearly influenced this change in clinical practice; however, other factors such as public and expert opinion, medicolegal considerations, and the behavior of pharmaceutical manufacturers also have had some effect. Some have speculated that a reduction in antidepressant use in youth is related to observed increases in suicide rates for this population. Although there has been an increase in the rate of adolescent suicide since 2003, such increases have also been seen in other age and demographic groups. The association between suicide rates and antidepressant use in adolescents or other groups is unclear, and is likely more correlational than causal. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of Bupropion on Depression Symptoms in a Smoking Cessation Clinical Trial.

Bupropion is an antidepressant shown to be efficacious for smoking cessation. This study examined the short- and long-term effects of bupropion (300 mg/day for 10 weeks) versus placebo on depression symptoms among 497 smokers attempting to quit in a randomized trial of bupropion plus behavioral counseling. Depression symptoms were assessed via the Center for Epidemiological Studies Depression Scale (L. Radloff, 1977) at baseline, end of treatment, and at 6-month follow-up. Baseline nicotine dependence level was assessed with the Fagerstrom Test for Nicotine Dependence (T. F. Heatherton, L. T. Kozlowski, R. C. Frecker, & K. O. Fagerstr?m, 1991). A regression model of depression symptoms demonstrated a significant interaction between nicotine dependence and treatment for the treatment phase and during follow-up. Depression symptoms did not mediate the effects of bupropion on abstinence at either time point. Highly nicotine-dependent smokers who receive bupropion are more likely to experience a decrease in depressive symptoms during active treatment but are also more likely to experience a rebound in depressive symptoms when bupropion is discontinued. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

准噶尔盆地玛湖凹陷二叠系烃源岩三环萜烷分布样式及影响因素

准噶尔盆地西北缘原油及烃源岩中生物标志物以高丰度的三环萜烷系列为典型特征,其分布样式的差异一直被当作研究本区原油成因类型及油-源对比的典型指标。通过对烃源岩样品的系统地球化学分析,认为本区风城组源岩（P₁f）主要以三环萜烷（C₂₀,C₂₁,C₂₃）呈“上升型”为特征,泥质岩类与碳酸盐岩类相比C₂₄,C₂₅三环萜烷含量较高;下乌尔禾组（P₂w）源岩和佳木河组（P₁j）源岩样品三环萜均呈“下降型”分布特征。通过对源岩镜下进行观察和加水热模拟实验等方法,分别探讨了沉积环境与母质类型、成熟度及排烃作用对三环萜分布样式的影响,认为P₁f和P₂w源岩中三环萜烷的分布主要受控于沉积环境和母质类型的原生差异。P₁f源岩有机质多源于本地沉积的藻类及细菌,沉积环境属于蒸发、还原的咸化湖沉积;P₂w源岩中外来有机质含量相对较多,沉积环境属于淡水还原环境。P₁j源岩整体热演化程度较高,有机质炭化作用强烈;埋藏成熟演化在有机质处于成熟-高熟阶段内对三环萜烷分布样式影响不大,若达到过熟阶段则会造成低碳数三环萜烷（C₂₀,C₂₁）含量增加;排烃作用对三环萜烷影响相对较小,不改变其分布样式。