3 research outputs found

    血管紧张素- (1- 7)预处理减轻大鼠离体心脏缺血再灌注损伤

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    【目的】 探讨较大剂量血管紧张素- (1- 7) 预处理对大鼠心肌缺血再灌注损伤的影响及其信号机制。【方法】48 只 SD 大鼠随机分为 4 组, 每组 12 只: 缺血再灌注对照组、血管紧张素- (1- 7)预处理组、血管紧张素- (1- 7)预处理加磷脂酰肌醇- 3 激酶( PI3K) 抑制剂 Wortmannin 处理组、Wortmannin 处理对照组, 观察较大剂量血管紧张素- (1- 7)预处理对大鼠离体缺血再灌注心脏左心室收缩压、冠状动脉流量、肌酸磷酸激酶和乳酸脱氢酶释放、心肌梗死范围以及心肌蛋白激酶 B( Akt) 、糖原合成酶激酶- 3β( GSK- 3β) 磷酸化的影响。【结果】与缺血再灌注对照组相比, 血管紧张素- (1- 7)预处理组心脏左心室收缩压、冠状动脉流量显著提高, 冠状动脉循环流出液中肌酸磷酸激酶、乳酸脱氢酶含量降低, 心肌梗死范围减小, 心肌磷酸化 Akt( Ser473) 、磷酸化 GSK-3β( Ser9) 水平增高, PI3K 抑制剂Wortmannin 能够抑制血管紧张素- (1- 7)预处理所致的Akt、GSK- 3β磷酸化, 但只能部分消除血管紧张素- (1- 7)预处理的心脏保护效应。【结论】较大剂量血管紧张素- (1- 7)预处理能够减轻大鼠离体心脏缺血再灌注损伤, PI3K/Akt/GSK- 3β信号通路参与介导血管紧张素- (1- 7) 预处理的心脏保护作用

    中国毒理学会会议论文集

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    目的:通过慢性应激模型和药理学手段研究NR2B亚基在抑郁症发病中的作用,选择性拮抗NR2B亚基的快速抗抑郁样作用及其神经生物学机制。方法:采用大鼠慢性应激抑郁模型,通过核团微注射方法研究内侧前额叶皮层内谷氨酸能NMDA受体不同亚基功能与抑郁样行为的关系。通过微透析技术及Western blot方法来检测内侧前额叶皮层内谷氨酸水平及相关分子的变化;通过多个抑郁模型及多种行为学测试(包括强迫游泳测试,&nbsp;</p

    Aripiprazole versus other atypical antipsychotics for schizophrenia

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    BACKGROUND: In most western industrialised countries, second generation (atypical) antipsychotics are recommended as first line drug treatments for people with schizophrenia. In this review we specifically examine how the efficacy and tolerability of one such agent - aripiprazole - differs from that of other comparable second generation antipsychotics. OBJECTIVES: To evaluate the effects of aripiprazole compared with other atypical antipsychotics for people with schizophrenia and schizophrenia-like psychoses. SEARCH METHODS: We searched the Cochrane Schizophrenia Group Trials Register (November 2011), inspected references of all identified studies for further trials, and contacted relevant pharmaceutical companies, drug approval agencies and authors of trials for additional information. SELECTION CRITERIA: We included all randomised clinical trials (RCTs) comparing aripiprazole (oral) with oral and parenteral forms of amisulpride, clozapine, olanzapine, quetiapine, risperidone, sertindole, ziprasidone or zotepine for people with schizophrenia or schizophrenia-like psychoses. DATA COLLECTION AND ANALYSIS: We extracted data independently. For dichotomous data we calculated risk ratios (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random-effects model. Where possible, we calculated illustrative comparative risks for primary outcomes. For continuous data, we calculated mean differences (MD), again based on a random-effects model. We assessed risk of bias for each included study. MAIN RESULTS: We included 12 trials involving 6389 patients. Aripiprazole was compared to olanzapine, risperidone and ziprasidone. All trials were sponsored by an interested drug manufacturer. The overall number of participants leaving studies early was 30% to 40%, limiting validity (no differences between groups).When compared with olanzapine no differences were apparent for global state (no clinically important change: n = 703, 1 RCT, RR short-term 1.00 95% CI 0.81 to 1.22; n = 317, 1 RCT, RR medium-term 1.08 95% CI 0.95 to 1.22) but mental state tended to favour olanzapine (n = 1360, 3 RCTs, MD total Positive and Negative Syndrome Scale (PANSS) 4.68 95% CI 2.21 to 7.16). There was no significant difference in extrapyramidal symptoms (n = 529, 2 RCTs, RR 0.99 95% CI 0.62 to 1.59) but fewer in the aripiprazole group had increased cholesterol levels (n = 223, 1 RCT, RR 0.32 95% CI 0.19 to 0.54) or weight gain of 7% or more of total body weight (n = 1095, 3 RCTs, RR 0.39 95% CI 0.28 to 0.54).When compared with risperidone, aripiprazole showed no advantage in terms of global state (n = 384, 2 RCTs, RR no important improvement 1.14 95% CI 0.81 to 1.60) or mental state (n = 372, 2 RCTs, MD total PANSS 1.50 95% CI -2.96 to 5.96).One study compared aripiprazole with ziprasidone (n = 247) and both the groups reported similar change in the global state (n = 247, 1 RCT, MD average change in Clinical Global Impression-Severity (CGI-S) score -0.03 95% CI -0.28 to 0.22) and mental state (n = 247, 1 RCT, MD change PANSS -3.00 95% CI -7.29 to 1.29).When compared with any one of several new generation antipsychotic drugs the aripiprazole group showed improvement in global state in energy (n = 523, 1 RCT, RR 0.69 95% CI 0.56 to 0.84), mood (n = 523, 1 RCT, RR 0.77 95% CI 0.65 to 0.92), negative symptoms (n = 523, 1 RCT, RR 0.82 95% CI 0.68 to 0.99), somnolence (n = 523, 1 RCT, RR 0.80 95% CI 0.69 to 0.93) and weight gain (n = 523, 1 RCT, RR 0.84 95% CI 0.76 to 0.94). Significantly more people given aripiprazole reported symptoms of nausea (n = 2881, 3 RCTs, RR 3.13 95% CI 2.12 to 4.61) but weight gain (7% or more of total body weight) was less common in people allocated aripiprazole (n = 330, 1 RCT, RR 0.35 95% CI 0.19 to 0.64). Aripiprazole may have value in aggression but data are limited. This will be the focus of another review. AUTHORS' CONCLUSIONS: Information on all comparisons are of limited quality, are incomplete and problematic to apply clinically. Aripiprazole is an antipsychotic drug with a variant but not absent adverse effect profile. Long-term data are sparse and there is considerable scope for another update of this review as new data emerges from the many Chinese studies as well as from ongoing larger, independent pragmatic trials
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