Preparation and local anaesthetic activity of benzotriazinone and benzoyltriazole derivatives

Two sets of benzotriazinone and benzoyltriazole derivatives were prepared and tested for local anaesthetic activity in comparison with lidocaine. Several of the prepared compounds exhibited a fairly good activity comparable or superior to that of lidocaine. The presence of a benzotriazinone or a benzoyltriazole moiety as an aromatic system was quite profitable for both the intensity and duration of activity. The acute toxicity in mice of the four most potent compounds of the series was also assessed. Compound 1b, which has an anaesthetic activity comparable to that of lidocaine, was also characterized by a more favourable therapeutic index. All compounds were tested in vitro to evaluate their negative chronotropic action in isolated rat right atria.     

Evidence that Dopaminergic Neurons are not Involved in the Negative Feedback Effect of Testosterone on Luteinizing Hormone in Rams in the Non-Breeding Season

In this study we tested the hypothesis that the negative feedback effects by testosterone on the secretion of luteinizing hormone (LH) in rams involves dopaminergic afferents to gonadotrophin-releasing hormone neurons operating via D(2) receptors in the non-breeding season. In the first experiment, three groups (n = 5) of rams were treated with an intravenous injection of vehicle or 10 or 20 mg of the dopaminergic D(2) antagonist pimozide and jugular venous samples were collected every 10 min for 3 h before and 3 h following treatment. The plasma was assayed for LH. Three groups of ewes (n = 4 to 5) were similarly treated. There were no significant effects of treatment of the rams with pimozide on the plasma concentrations of LH or LH pulse frequency or pulse amplitude and the response of individual rams in each group was inconsistent. In contrast, treatment of the ewes with 20 mg pimozide significantly (P<0.001) increased the mean (± SEM) plasma LH concentrations (pretreatment 0.37 ± 0.04; post-treatment 2.42±0.25 ng/ml) and decreased (P<0.001) the LH inter-pulse interval (pretreatment 180.0; post-treatment 88.0±11.1 min); the 10 mg dose of pimozide did not affect these parameters. In the second experiment, two groups of rams (n = 5) and ewes (n = 7) were treated with an intravenous injection of vehicle or 0.33 mg pimozide/kg liveweight and jugular venous samples were collected every 10 min for 2 h before and 6 h following treatment. As in the first experiment, the mean (± SEM) concentrations of plasma LH were not affected by treatment with pimozide in the rams (pretreatment 0.18 ± 0.25; post-treatment 0.43 ± 0.14 ng/ml) but were significantly (P<0.05) increased in the ewes (pretreatment 1.12±0.22; post-treatment 1.93 ± 0.23 ng/ml). In the third experiment, four adult rams were castrated and 3 weeks later each animal had two cannulae inserted to allow injection into the lateral cerebral ventricles. Vehicle or 100 μg pimozide was injected intracerebroventricularly and blood samples were collected as in the other experiments. A Latin Square design was used so that each animal received each treatment (n = 4). This procedure was repeated after the animals had been injected (intramuscularly) with 16 mg testosterone propionate twice daily for at least 7 days. Treatment with testosterone propionate significantly decreased (P < 0.001) the plasma concentrations of LH (pre-treatment 7.71±0.27; post-treatment 0.75 ± 0.27 ng/ml; mean ± SEM) and follicle-stimulating hormone (pre-treatment 79.61±8.47; post-treatment 42.53 ± 6.08 ng/ml; mean ± SEM) and increased the mean (± SEM) LH inter-pulse interval (53.14 ± 3.58 min pre-treatment and 292.5 ± 32.94 min post-treatment) but had no effect on the amplitude of LH pulses (pre-treatment 3.61 ± 0.36; post-treatment 1.86±1.76 ng; mean ± SEM). Pimozide had no effect on the plasma concentrations of gonadotrophins. These results suggest that, in the ram, dopaminergic neurons do not influence the gonadotrophin-releasing hormone neurons via D(2) receptors in the non-breeding season and are not involved in the negative feedback effect of testosterone on the secretion of gonadotrophins. Conversely, our data suggest that such a mechanism is integral to the negative feedback effects of oestradiol on LH in anoestrous ewes. Finally, it also appears that the steroid-independent suppression of the secretion of gonadotrophins during the non-breeding season in rams is not mediated via D(2) receptors.     

Combined screening of thymocytes using apoptosis-specific cDNA array and promoter analysis yields novel gene targets mediating TCDD-induced toxicity.

We have used pathway-specific cDNA arrays coupled with analysis of gene promoter regions to identify novel genes that may mediate the toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the thymus. C57BL/6 mice were injected ip with 50 microg/kg TCDD, and 3, 6, or 24 h later, RNA was extracted from the thymus and subjected to microarray analysis. Several members of the TNF and TNFR family were induced following TCDD exposure, including receptor/ligand pairs Ltbeta-R/LIGHT, OX40/OX40L and TNF-alpha/TNFR1. In addition, Fas and CD30 were also upregulated. Pro-apoptotic bcl-2 gene family members Bax and Hrk, among others, were also induced, as were pro-survival bcl-2 family genes Bcl-x and Bcl-w. Cell-cycle regulator p21Cip1 was also induced. In addition, we analyzed the promoter regions of genes induced by TCDD for the presence of dioxin-responsive elements (DREs). The Fas and LIGHT gene promoters were found to contain DREs as analyzed by Matinspector Web-based search algorithm. Furthermore, binding of the aryl hydrocarbon receptor (AhR) to the DREs present on these genes was confirmed by chromatin immunoprecipitation. Given that several of the genes, including Fas, LIGHT, and CD30 are involved in negative selection of T cells in the thymus, our studies suggest that TCDD-induced upregulation of these genes may enhance negative selection leading to thymic atrophy.     

以循证为基础的阶梯式心理护理对乳腺癌化疗患者负性心理的影响研究

目的 探讨以循证为基础的阶梯式心理护理(SCM)对乳腺癌化疗患者负性心理的影响.方法 采取方便抽样的方法,将76例乳腺癌化疗患者随机分为对照组和观察组各38例.对照组实施乳腺癌常规心理护理和出院后随访,观察组在对照组措施的基础上实施阶梯式心理干预措施,包括1周观察评估、2周指导性自我管理、4周一对一健康指导、4周专业心...     

Brain activation during cognitive reappraisal depending on regulation goals and stimulus valence

Neural bases of cognitive reappraisal may depend on the direction of regulation (up- or downregulation) and stimulus valence (positive or negative). This study aimed to examine this using a cognitive reappraisal task and conjunction analysis on a relatively large sample of 83 individuals. We identified regions in which activations were common for all these types of emotion regulation. We also investigated differences in brain activation between the ‘decrease’ and ‘increase’ emotional response conditions, and between the regulation of negative and positive emotions. The common activation across conditions involved mainly the prefrontal and temporal regions. Decreasing emotions was associated with stronger involvement of the dorsolateral prefrontal cortex, while increasing with activation of the amygdala and hippocampus. Regulation of negative emotions involved stronger activation of the lateral occipital cortex, while regulation of positive emotions involved stronger activation of the anterior cingulate cortex extending to the medial prefrontal cortex. This study adds to previous findings, not only by doing a conjunction analysis on both emotional valences and regulation goals, but also doing this in a bigger sample size. Results suggest that reappraisal is not a uniform process and may have different neural bases depending on regulation goals and stimulus valence.     

试论三阴性乳腺癌阴虚证及方药治疗

总结三阴性乳腺癌的临床病理特征以及三阴性乳腺癌阴虚证的病机特点,分析三阴性乳腺癌中医体质证候分型,发现阴虚证在三阴性乳腺癌病例中所占的比率较低,探讨阴虚在三阴性乳腺癌发病中的重要作用,归纳三阴性乳腺癌阴虚证的中医药治疗方药,包括名老中医的经验举隅和经典名方的运用,为临床选择滋阴方治疗三阴性乳腺癌提供经验参考。     

培育颗粒对人绒毛滋养细胞侵袭与增殖的作用

目的观察培育颗粒对人绒毛滋养细胞的侵袭和增殖功能的影响。方法取人妊娠5~10周正常胎盘绒毛,进行滋养细胞培养。正常23~25 d雌性SD大鼠药物灌胃,取药理血清。培养液加20%血清,分组培养48 h后检测指标。用Transwell侵袭实验检测培育颗粒对滋养细胞侵袭功能的影响,MTT法检测培育颗粒对滋养细胞增殖能力的影响,流式细胞术检测培育颗粒对滋养细胞增殖核抗原(PCNA)表达的影响。结果Transwell侵袭实验检测结果表明,培育颗粒血清各剂量组与正常组侵袭细胞数均有差异,中剂量组侵袭细胞数最多。MTT法检测结果表明,培育颗粒血清各剂量组与正常组吸光度均有差异,中剂量组吸光度最高。流式细胞术检测结果表明,培育颗粒血清各剂量组与正常组PCNA阳性率均有差异,中剂量组PCNA阳性率最高。结论培育颗粒可促进人绒毛滋养细胞侵袭与增殖功能,可能与负反馈调节有关。     

CA153与CEA在三阴乳腺癌及非三阴乳腺癌预后中的比较分析

目的 探讨血清CA153与CEA在三阴乳腺癌及非三阴乳腺癌中表达水平的差异,并分析血清中CA153与CEA水平差异与患者预后情况的关系.方法 选取2005年1月至2012年6月经临床病理学确诊的三阴乳腺癌患者120例(三阴组)及非三阴乳腺癌患者575例(非三阴组),采用电化学发光法检测两组患者血清CA153、CEA含量,并分析这两种肿瘤标志物水平变化与患者总生存期、无进展生存期的关系.结果 三阴组患者血清CA153含量为(47.06±45.63) U/ml,明显高于非三阴组患者的(30.38±28.57) U/ml,差异有统计学意义(P＜0.01),而三阴组的CEA含量为(10.11±9.54) ng/ml,高于非三阴组的(7.03±6.87) ng/ml(P＜0.05).5年内生存分析结果表明,血清CA153＜47.06 U/ml,CEA＜10.11 ng/ml的三阴组患者和血清＜30.38 U/ml,CEA＜ 7.03 ng/ml非三阴组患者存在明显的无疾病进展时间和生存优势,差异有统计学意义(P＜0.05).结论 血清CA153与CEA可作为三阴乳腺癌及非三阴乳腺癌患者预后情况的预测指标之一.