Posttraumatic stress disorder arising after road traffic collisions: Patterns of response to cognitive–behavior therapy.

Road traffic collisions (RTCs) are common precipitants of posttraumatic stress disorder (PTSD). Two preliminary studies suggest that cognitive–behavior therapy (CBT) is, on average, effective in treating this disorder, although the major patterns of treatment outcome remain to be identified. Such outcomes might include treatment response, partial response, and response followed by relapse. To identify these patterns, 50 people with RTC-PTSD completed a 12-week course of CBT, with outcome assessment extending to 3-month follow up. Dynamic cluster analyses revealed 2 replicable patterns of outcome: one for responders (n?=?30) and one for partial responders (n?=?20). Partial responders, compared with responders, tended to have more severe pretreatment numbing symptoms and greater anger about their RTC, along with lower global levels of functioning, greater pain severity and interference, and greater depression and were more likely to be taking psychotropic medications. Responders and partial responders did not differ in homework adherence, number of sessions attended, therapist effects, or stressors occurring during therapy or in the presence or absence of RTC-related litigation. Implications for enhancing treatment outcome are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

抗抑郁药的信号转导机制

抗抑郁药的作用机制目前尚不明确, 传统单胺递质理论和受体理论都不能充分解释抗抑郁药的临床效应滞后现象。近年提出抗抑郁药的信号转导机制, 认为抗抑郁药是以G 蛋白为分子基础, 神经递质受体和G 蛋白为作用环节, 最终影响细胞内的信号转导并产生磷酸化作用增加、神经营养因子增多、神经发生增加等相关效应, 从而发挥抗抑郁作用。影响细胞内信号转导并产生相关效应需要的时间, 与抗抑郁药的临床效应滞后时间相吻合, 从而使抗抑郁药的滞后现象有了合理解释。这个机制的提出有助于抗抑郁新药的发展, 为研制安全、有效的新药指明了方向, 同时也为抑郁症生物学病因的阐明提供了必要信息。     

Molecular Recognition of the HPLC Whelk-O1 Selector towards the Conformational Enantiomers of Nevirapine and Oxcarbazepine

The presence of stereogenic elements is a common feature in pharmaceutical compounds, and affording optically pure stereoisomers is a frequent issue in drug design. In this context, the study of the chiral molecular recognition mechanism fundamentally supports the understanding and optimization of chromatographic separations with chiral stationary phases. We investigated, with molecular docking, the interactions between the chiral HPLC selector Whelk-O1 and the stereoisomers of two bioactive compounds, the antiviral Nevirapine and the anticonvulsant Oxcarbazepine, both characterized by two stereolabile conformational enantiomers. The presence of fast-exchange enantiomers and the rate of the interconversion process were studied using low temperature enantioselective HPLC and VT-NMR with Whelk-O1 applied as chiral solvating agent. The values of the energetic barriers of interconversion indicate, for the single enantiomers of both compounds, half-lives sufficiently long enough to allow their separation only at critically sub-ambient temperatures. The chiral selector Whelk-O1 performed as a strongly selective discriminating agent both when applied as a chiral stationary phase (CSP) in HPLC and as CSA in NMR spectroscopy.     

Effects of Antidepressants on IP-10 Production in LPS-Activated THP-1 Human Monocytes

Major depressive disorder and cardiovascular disease are common serious illnesses worldwide. Selective serotonin reuptake inhibitors and norepinephrine-dopamine reuptake inhibitors may reduce the mortality of cardiovascular disease patients with comorbid depression. Interferon-γ-inducible protein 10 (IP-10), a type 1 T helper cell (Th1)-related chemokine, contributes to manifestations of atherosclerosis during cardiovascular inflammations; however, the pathophysiological mechanisms linking cardiovascular disease and effective antidepressants have remained elusive. We investigated the in vitro effects of six different classes of antidepressants on the IP-10 chemokine expression in lipopolysaccharide (LPS)-stimulated monocytes, and their detailed intracellular mechanisms. The human monocytes were pretreated with antidepressants (10⁻⁸–10⁻⁵ M) before LPS-stimulation. IP-10 was measured by enzyme-linked immunosorbent assay (ELISA) and then intracellular signaling was investigated using Western blotting and chromatin immunoprecipitation. Fluoxetine and bupropion suppressed LPS-induced IP-10 expression in monocytes, and they had no cytotoxic effects. Furthermore, fluoxetine inhibited LPS-induced IP-10 expression via the mitogen-activated protein kinase (MAPK)-p38 pathway. Fluoxetine and bupropion could not only treat depression but also reduce Th1-related chemokine IP-10 production in human monocytes. Our results may indicate a possible mechanism related to how particular antidepressants reduce the risk of cardiovascular disease.     

HPLC-Q-TOF/MS测定保健食品中19种抗抑郁药物

目的：建立保健食品中非法添加19种抗抑郁药物的高效液相色谱—四极杆—飞行时间质谱快速筛查定性与定量分析方法。方法：样品采用甲醇溶液进行超声提取,提取液经C₁₈色谱柱分离,以0.1%甲酸水溶液—乙腈为流动相,梯度洗脱,在电喷雾正离子模式下进行检测,检测结果以试验方法建立的19种抗抑郁药物一级精确质量数据库和二级碎片质谱库进行筛查匹配。结果：在5～100 μg/L质量浓度范围内,19种目标化合物线性关系良好,相关系数为0.988 7~0.999 9,在2,5,10 μg/kg 3个加标水平下样品的回收率为81.2%～98.6%,相对标准偏差为0.9%～6.7%。结论：所建立的方法适用于保健食品中非法添加抗抑郁药物的快速筛查定性与定量分析。     

含三环醚系物质UNIFAC基团新交互作用参数的拟合

研究了ＵＮＩＦＡＣ基团贡献法中三环醚分子基团的划分法，用文献实测汽液平衡（ＶＬＥ）数据拟合出６对三环醚基的新交互作用参数，用本文提出的基团划分法和交互作用参数，成功地预测了９对含三环醚物质的ＶＬＥ数据。     

抗抑郁药度洛西汀的合成方法综述

抗抑郁药度洛西汀因其化学稳定、副作用小、药效明显优于其它抗抑郁药而具有广阔的发展前景,文章详细叙述了近年来国内外常见的几种合成方法,评述了各自优缺点,得出了一条最具竞争力的合成路线:以(S)-3-二甲胺基一1-2-噻吩基)-1-丙醇为原料,经拆分、醚化、酯化、水解得到目标。     

Trace Amine-Associated Receptor 1 Contributes to Diverse Functional Actions of O-Phenyl-Iodotyramine in Mice but Not to the Effects of Monoamine-Based Antidepressants

Trace Amine-Associated Receptor 1 (TAAR1) is a potential target for the treatment of depression and other CNS disorders. However, the precise functional roles of TAAR1 to the actions of clinically used antidepressants remains unclear. Herein, we addressed these issues employing the TAAR1 agonist, o-phenyl-iodotyramine (o-PIT), together with TAAR1-knockout (KO) mice. Irrespective of genotype, systemic administration of o-PIT led to a similar increase in mouse brain concentrations. Consistent with the observation of a high density of TAAR1 in the medial preoptic area, o-PIT-induced hypothermia was significantly reduced in TAAR1-KO mice. Furthermore, the inhibition of a prepulse inhibition response by o-PIT, as well as its induction of striatal tyrosine hydroxylase phosphorylation and elevation of extracellular DA in prefrontal cortex, were all reduced in TAAR1-KO compared to wildtype mice. O-PIT was active in both forced-swim and marble-burying tests, and its effects were significantly blunted in TAAR1-KO mice. Conversely, the actions on behaviour and prefrontal cortex dialysis of a broad suite of clinically used antidepressants were unaffected in TAAR1-KO mice. In conclusion, o-PIT is a useful tool for exploring the hypothermic and other functional antidepressant roles of TAAR1. By contrast, clinically used antidepressants do not require TAAR1 for expression of their antidepressant properties.     

抗抑郁药物联合短期无抽搐电休克治疗对抑郁症疗效及认知功能的影响

目的:探讨抗抑郁药物联合短期无抽搐电休克（MECT）治疗重性抑郁症对其急性期及远期临床疗效及认知功能的影响。方法:将重性抑郁症患者共132例分为试验组（58例）与对照组（74例）,试验组采用抗抑郁药和短期无抽搐电休克治疗,对照组仅采用抗抑郁药物治疗。急性期分别观察患者在治疗第1天、第1周末、第2周末、第3周末的汉密尔顿抑郁量表（HAMD）和韦氏记忆量表（WMS）评分结果,用副反应量表（TESS）来评估治疗总的副反应情况,同时记录患者住院天数。随访期分别观察患者在治疗第6月末和第12月末的HAMD和WMS量表结果,并记录患者的复发率。 结果:试验组在第2周末和第3周末的HAMD评分要好于对照组（P<0.05）,且两组TESS总分比较无统计学差异。试验组住院天数要明显少于对照组（P<0.05）。WMS评分上试验组在第3周时要差于对照组（P<0.05）,但在第6月末和第12月末的比较无统计学差异。试验组在第12月内的复发率要低于对照组（P<0.05）。 结论:在足量抗抑郁药治疗的同时联合短期MECT治疗,是一种行之有效的治疗方案,既能迅速彻底地改善抑郁症患者的临床症状,减少患者住院天数及远期复发风险,又能避免MECT治疗次数过多导致的认知功能损害问题。     

水环境中典型抗抑郁药物的分布与去除现状

抗抑郁药物是一类具有生物毒性的新型环境污染物,近年来在水环境中频繁检出,已引起水处理界的广泛关注。介绍了典型抗抑郁药物的来源及分布现状,并以检出频率较高的西酞普兰和文拉法辛为例,综述了其在污水处理厂中的去除现状,以及高级氧化技术对其的降解效果。由于我国对水环境中的抗抑郁类药物的研究尚处于起步阶段,因此在今后的研究中有必要关注典型抗抑郁药物在污水处理过程中的降解机制,探究污水成分对降解过程的影响。