G蛋白与精神障碍

Ｇ蛋白与精神障碍武汉市精神卫生中心（４３００２２）徐汉明鸟嘌呤核苷酸结合蛋白（Ｇ蛋白）是一类存在于细胞膜与受体偶联的蛋白质。目前发现的Ｇ蛋白有五种，即Ｇｓ，Ｇｉ、Ｇｐ、Ｇｔ和Ｇｏ。它们的分子结构相似，都由α、β和γ三个亚基组成。其中α亚基具有三磷酸鸟...     

G蛋白与阿片类依赖

本介绍了Ｇ蛋白的功能，其各亚型在阿片类物质依赖时的变化以及与效应器酶的关系，提示Ｇ蛋白在阿片类依赖分子机理中的作用。     

G蛋白与情感障碍

本介绍了Ｇ蛋白的结构，分型和功能，阐述了有关情感性精神障碍时Ｇ蛋白的变化以及锂，抗抑郁药对Ｇ蛋白的作用的研究结果。提示Ｇ蛋白与情感障碍病理生理机制及其治疗药物作用的生化机制之间存在密切联系。     

G蛋白与情感障碍

本文介绍了Ｇ蛋白的结构、分型和功能，阐述了有关情感性精神障碍时Ｇ蛋白的变化以及锂、抗抑郁药对Ｇ蛋白的作用的研究结果。提示Ｇ蛋白与情感障碍病理生理机制及其治疗药物作用的生化机制之间存在密切联系。     

G蛋白与阿片类依赖

本文介绍了Ｇ蛋白的功能、其各亚型在阿片类物质依赖时的变化以及与效应器酶的关系，提示Ｇ蛋白在阿片类依赖分子机理中的作用。     

PAI-1 4G/5G基因多态性与脑出血的相关性研究

P>0.05).结论 PAI-14G/5G基因多态性可能与脑出血无关,与脑血管病主要危险因素高血压病、高脂血症及性别无关.     

The Toulouse Gérontopôle Research Center: report of activities, 2007-2011

The formation of the first Gerontopole in Toulouse was a response to a mission letter sent by French Ministers of Health on February 2007. The mission of the Toulouse Gerontopole is based around three major axes: 1) To facilitate the access of frail elderly people to innovative therapy and clinical research: the Gérontop?le set up the national network for clinical investigation into Alzheimer's disease (AD) funded through the CeNGEPS (National Centre For Management of Trials on Health Products) calls for proposals since July 2008. In addition, the Gérontop?le coordinates several national clinical trials with promising drugs with potential effect on the mechanisms and evolution of AD and actively participates in studies on biomarkers; 2) To develop health promotion actions and prevention trials for healthy elderly people, through the Institute of Aging: the Gérontop?le has implemented the GuidAge (Phase III trial concerning the efficiency of Ginkgo Biloba on the impact and delay of appearance of an Alzheimer type dementia) and MAPT (Multi-domain Alzheimer Preventive Trial) studies on prevention of AD and cognitive decline. It is curently working on the new generation of preventive trials based on biomarkers; 3) To develop clinical research for dependant elderly people, through the implementation of the REHPA research network including 240 nursing homes in France. In December 2009, additional grants were delivered by the French government to extend the three research axes for two more years, and establish a charter of quality for geriatric care in relation with the administration and relevant agencies.     

Immunoglobulin G level variations in treated chronic inflammatory demyelinating polyneuropathy: clues for future treatment regimens?

Intravenous immunoglobulins (IVIg) are effective for treating chronic inflammatory demyelinating polyneuropathy (CIDP), although treatment needs are variable and need to be individualized. Dose and frequency requirements are not currently predictable in advance. In Guillain–Barré syndrome, IVIg interpatient pharmacokinetic variations have been demonstrated in relation to clinical outcome. We studied 15 patients with CIDP following two routine courses of IVIg. IgG levels were assessed pretreatment and 14 days post-treatment. Best clinical response (BCR) was ascertained in each case, predefined, according to individual patients’ circumstances, on the 10 m walk, or MRC sum score, or Jamar grip dynamometry. Correlations between IgG level variations, doses administered, weight, body mass index, BCR and infusion interval were determined. Postinfusion rise in IgG levels were correlated in individual patients (p = 0.005), but interpatient variability was high. No correlations were ascertained between IgG level variation and weight, body mass index, BCR, total dose of IVIg administered, or dose of IVIg administered per kilogram per week. There were significant correlations between total dose administered and post-infusion IgG level at 14 days (p = 0.004) and between infusion interval and mean rise in IgG level (p = 0.001) These findings suggest significant variability in IgG metabolism between patients, unrelated to minimal effective dose administered, weight, body mass index or degree of functional improvement. Required frequency of IVIg infusions may, however, importantly relate to patient-specific post-infusion rise in IgG levels hence possibly explaining inter-patient differences in treatment frequency needs. IgG level monitoring may be helpful in establishing optimum treatment regimens in individual cases.     

G蛋白的精神生物学意义

鸟苷酸结合蛋白(G蛋白)是所有膜信号系统传导的必经之路,其功能改变能放大和衰减神经信号,本文介绍了该蛋白的性能,讨论了其在精神疾病和精神药理中的作用。     

G蛋白信号转导异常与阿尔茨海默病

AD是一种以进行性认知功能减退为特征的神经退行性疾病.流行病学调查表明:在65岁以上人群中AD的发病率为5%～10%,85岁以上的老年人中发病率约为25%[1].随着人口老龄化趋势的进展,AD已成为威胁人类生命的主要疾病,其致死率仅次于心脏病、肿瘤和中风.     

TAFI基因启动子区-2345 2G/1G多态性与脑梗死的关系

目的分析中国汉族人群TAFI基因启动子区-2345 2G/1G与动脉粥样硬化性脑梗死发病的关系。方法选择225例脑梗死（病例组）和184例健康体检者（对照组）为对象,应用等位基因特导性聚合酶链反应分析方法（AS-PCR）检测-2345 2G/1G多态性。结果 TAFI-2345 2G/1G在病例组的1G等位基因频率为42.9%,对照组为50.8%,2组间差异有统计学意义（P=0.024）;病例组1G/1G基因型频率为15.1%,对照组为24.5%,2组间差异有统计学意义（P=0.017）。经Logis-tic回归分析,TAFI-2345 1G/1G基因型与脑梗死的发病有独立相关性。结论 TAFI-2345 2G/1G多态性与动脉粥样硬化性脑梗死的发病有关联,1G/1G基因型可能使脑梗死患病风险降低。     

Kinetic modeling of Na+-induced, Gβγ-dependent activation of G protein-gated K+ channels

G protein-activated K(+)(GIRK) channels are activated by numerous neurotransmitters that act on Gi/o proteins, via a direct interaction with the Gbetagamma subunit of G proteins. In addition, GIRK channels are positively regulated by intracellular Na(+) via a direct interaction (fast pathway) and via a GGbetagamma-dependent mechanism (slow pathway). The slow modulation has been proposed to arise from the recently described phenomenon of Na(+)-induced reduction of affinity of interaction between GalphaGDP and Gbetagamma subunits of G proteins. In this scenario, elevated Na(+) enhances basal dissociation of G protein heterotrimers, elevating free cellular Gbetagamma and activating GIRK. However, it is not clear whether this hypothesis can account for the quantitative and kinetic aspects of the observed regulation. Here, we report the development of a quantitative model of slow, Na(+)-dependent, G protein-mediated activation of GIRK. Activity of GIRK1F137S channels, which are devoid of direct interaction with Na(+), was measured in excised membrane patches and used as an indicator of free GGbetagamma levels. The change in channel activity was used to calculate the Na(+)-dependent change in the affinity of G protein subunit interaction. Under a wide range of initial conditions, the model predicted that a relatively small decrease in the affinity of interaction of GalphaGDP and GGbetagamma (about twofold under most conditions) accounts for the twofold activation of GIRK induced by Na(+), in agreement with biochemical data published previously. The model also correctly described the slow time course of Na(+) effect and explained the previously observed enhancement of Na(+)-induced activation of GIRK by coexpressed Galphai3. This is the first quantitative model that describes the basal equilibrium between free and bound G protein subunits and its consequences on regulation of a GGbetagamma effector.     

PAI—1启动子区4G／5G基因多态性与脑卒中的相关研究

目的 探讨纤溶酶原激活物抑制物－1（PAI－1）启动子区基因多态性与脑卒中的关系。方法 通过 多聚酶链反应（PCR）技术和发色底物法（RLISA）,测定96例脑卒中患者和60名健康对照者的白细胞PAI－1启动子区4G／5G多态性位点的基因型及血浆PAI－1活性。结果 脑梗死（CI）组血浆PAI－1活性明显高于脑出血（CH）组及对照组,CI和CH组中均以纯合子4G／4G基因型患者的PAI－1血浆活性水平为最高,5G／5G基因型最低,杂合子4G／5G基因型居中;4G纯合子基因型与其它二型 之间比较差异均有显著意义,4G／5G与5G／5G基因型之间比较无显著意义。CI组4G／4G纯合子基因型与对照组比较有显著性差异（均P＜0．05）,CI组基因型与CH组及CH组与对照组基因型比较均无统计学意义（P＞0．05）。CI组女性4G纯合子基因型患者血浆PAI－1活性与同型男性患者比较有显著性差异（P＜0．05）。结论 纯合子4G／4G基因型可能是CI发病的危险因素之一,4G纯合子个体可能具有较高的CI发病倾向,尤其可能与女性CI发病相关。     

普鲁卡因青霉素G注射后的精神障碍

水溶性普鲁卡因青霉素G肌注后可发生一种急性中毒性障碍,称之为Hoigen氏综合征。神经系统表现有精神障碍和癫痫发作,轻者表现为精神错乱、眩晕和味觉、视觉异常。多数还伴有心动过速和血压增高,但没有任何变态反应的表现。Hoigen综合征较罕见,回顾报告其发生率为3/1000,前瞻性