耐药性癫患者脑组织线粒体mMDHNDUFC_2基因表达异常

目的研究耐药性癫患者脑细胞线粒体mMDH、NDUFC2表达,探讨其在耐药性癫癎形成中的作用。方法分别提取48例耐药性癫癎患者、8例非耐药性癫患者及8例对照组脑组织标本的总RNA后,用基因芯片对其进行扫描,随后用荧光定量PCR技术进行验证。结果发现与线粒体功能有关的基因mMDH、NDUFC2在耐药性癫癎中显著下调,荧光定量RT—PCR验证结果与基因芯片一致。结论脑细胞线粒体基因mMDH、NDUFC2表达异常可能通过能量代谢及神经元坏死参与了耐药性癫癎的形成。     

耐药性癫(癎)患者伴有(癎)样放电的脑组织中SCN8A基因产物的异常表达

目的观察电压门控钠通道SCN8A(sodium channel voltage-gated type VIII alpha,SCN8A)基因在耐药性癫患者脑组织中的表达,探讨其与耐药性癫的关系。方法在基因芯片研究的基础上,采用免疫组织化学、免疫荧光组织化学技术,分析比较40例耐药性癫患者手术切除脑组织标本中SCN8A基因编码的产物钠通道蛋白Nav1.6的表达水平,并与20名对照组进行比较。结果发现SCN8A在耐药性癫患者脑组织中表达上调,与对照组比较有统计学意义(P<0.05)。结论SCN8A基因在耐药性癫脑组织中表达上调,可能与耐药性癫中样放电的产生和(或)传播有关。     

耐药性颞叶癫癎的研究进展

1耐药性癫?的概述
　　癫?是多种原因所致的慢性脑部疾病,其特征为脑部神经元异常过度放电引发身体某一部分或整个肢体非自主性抽搐,有时伴有意识丧失和尿便失禁。世界卫生组织的数据表明,全球约有5000万癫?患者［1］,而我国就有癫?患者900万人,且每年新增癫?患者40万人［2］。癫?在卫生保健需求、过早死亡以及丧失工作生产力方面给社会经济带来严重的负担。     

耐药性癫癎患者的载脂蛋白E（ApoE）基因多态性分析

目的 研究耐药性癫痫患者的载脂蛋白E基因多态性，并探究影响耐药性癫癎形成机制的遗传因素。方法 取耐药性癫癎患者肘静脉血，用PCR-RFLP技术检测ApoE基因多态性，并与非耐药性癫癎和正常对照组进行比较分析。结果 耐药性癫癎组中ε4等位基因的频率为（16．9），明显高于非耐药性癫癎组（8．2）和正常对照组，其差异有统计学意义（P〈0．05），而ε2，ε3等位基因的频率三组之间差异无统计学意义（P〉0．05）；病例组与正常对照组ApoE基因多态性有显著性差异（P〈0．01）。结论 ApoEε4等位基因可增加耐药性癫癎发生的危险性。     

耐药性癫癎患者术后脑组织中Tau蛋白的表达

目的研究Tau蛋白在耐药性癫癎患者脑组织中的表达,探讨其在耐药性癫癎发病机制中的作用。方法采用免疫组化法检测48例耐药性癫癎患者海马及颞叶皮层中Tau蛋白的表达,同步观察海马苔藓纤维芽生,并与对照组进行比较。结果耐药性癫癎组和对照组脑组织中总Tau蛋白表达无明显差异,而磷酸化Tau蛋白在耐药性癫癎患者海马CA3区(0·0450±0·0115)及齿状回内分子层(0·0463±0·0120)表达增多,同步伴有海马苔藓纤维芽生(耐药性癫癎组:3·18±0·35,对照组:0·61±0·19)。结论磷酸化Tau蛋白表达增强可能是耐药性癫癎患者海马突触重建的重要机制,改变磷酸化Tau蛋白的表达有可能改善耐药性癫癎患者的预后。     

MCP-1在难治性癫(癎)患者脑组织中的表达

目的 了解难治性癫(癎)患者脑组织中单核细胞趋化蛋白-1(monocyte chemoattractant protein-1,MCP-1)的表达,探索其在难治性癫(癎)发病机制中的作用.方法在基因芯片扫描获阳性结果基础上,用免疫组织化学方法 研究40例难治性癫(癎)患者脑组织中MCP-1的表达,并与对照组进行比较.结果 基因芯片扫描显示MCP-1 mRNA表达上调,免疫组化结果进一步证实MCP-1在难治性癫(癎)患者脑组织中的表达较对照组明显增多(P＜0.05).结论 MCP-1在难治性癫(癎)的发病机制中可能起着重要作用,阻断MCP-1有可能改变难治性癫(癎)的预后.     

难治性癫癎患者脑组织突触囊泡回收相关蛋白的表达

目的研究难治性癫患者脑组织内突触囊泡循环再生相关蛋白的表达,以探讨难治性癫的成因及其他可能的发病机制。方法用免疫组化、Western印迹法检测与突触囊泡循环再生密切相关的网格蛋白(clathrin)、突触囊泡膜蛋白Ⅰ(synaptotagminⅠ)在难治性癫患者脑部的表达,并与健康人群比较。结果免疫组化显示与突触囊泡循环再生密切相关的网格蛋白[在海马为(0·173±0·019),颞叶为(0·186±0·024)]、突触囊泡膜蛋白Ⅰ[在海马为(0·188±0·019),颞叶为(0·190±0·017)]在难治性癫患者脑部表达较健康人增强(P<0·05),Western印迹显示网格蛋白、突触囊泡膜蛋白Ⅰ在难治性癫组增加,电泳条带明显增宽,且免疫组化显示难治性癫患者脑组织中网格蛋白、突触囊泡膜蛋白Ⅰ表达随病程的延长而有增强的趋势。结论难治性癫患者脑组织内存在突触囊泡循环再生过程强化。     

抗癫药物对妊娠癫癎患者子代的致畸风险

目的:旨在评估抗癫癎药物(AEDs)对妊娠癫癎患者子代出现先天畸形的风险。方法:对妊娠癫癎患者采用登记和随访研究,分析其孕期AEDs用药情况、癫癎发作、妊娠结局及子代出现畸形的风险。结果:入选105例妊娠癫癎患者。服用AEDs患者79/105例(75.2%),未服用AEDs患者26/105例(24.8%)。单药治疗60/79例(75.9%),其中1/60例(1.7%)流产;患者子代中2/60例(3.3%)先天性畸形(1例服用卡马西平,出现先天性心脏动脉导管未闭;1例服用拉莫三嗪,出现无胚心)。联合用药19/79例(24.1%),子代无先天畸形出现。未服用AEDs患者中有2/26例(7.7%)流产,其余患者子代未出现先天畸形。结论:妊娠癫癎孕妇多数于孕期仍服用AEDs,且以单药治疗居多;使用AEDs(分别为卡马西平和拉莫三嗪)患者子代出现2例先天性畸形;丙戊酸钠易致畸但仍在妊娠癫癎中经常使用,本研究中服用丙戊酸钠孕妇未出现子代先天性畸形。     

P-gp与癫(癎)耐药相关性研究进展

P-gp是由ABCB1基因编码的能量依赖性跨膜外向转运蛋白,在灶组织内的表达明显增加,影响AEDs通过血脑屏障,降低灶组织内AEDs浓度.给予P-gp抑制剂,不仅可以提高耐药细胞内AEDs浓度,也能增加灶组织内AEDs浓度,并扭转癫(癎)的耐药性.越来越多的研究从P-gp的结构、功能和过表达等方面阐述与癫(癎)耐药的相关性,现就这一方面的研究进展作一综述.     

P-gp与癫(癎)耐药相关性研究进展

P-gp是由ABCB1基因编码的能量依赖性跨膜外向转运蛋白,在灶组织内的表达明显增加,影响AEDs通过血脑屏障,降低灶组织内AEDs浓度.给予P-gp抑制剂,不仅可以提高耐药细胞内AEDs浓度,也能增加灶组织内AEDs浓度,并扭转癫(癎)的耐药性.越来越多的研究从P-gp的结构、功能和过表达等方面阐述与癫(癎)耐药的相...     

神经生长相关蛋白-43在耐药性颞叶癫痫患者脑组织中的表达及其意义

目的 研究神经生长相关蛋白-43（growth-associated protein-43,GAP-43）在耐药性颞叶癫痫患者脑组织中的表达,探索其在耐药性癫痫中的作用.方法 按随机化原则从我科建立的耐药性癫痫患者术后脑组织库中随机抽取42例耐药性颞叶癫痫患者术后脑组织标本,用免疫组化法检测生长相关蛋白-43在耐药性颞叶癫痫患者脑组织中的表达,并与对照组进行比较.结果 发现GAP-43在耐药性颞叶癫痫患者脑组织中的表达比对照组明显增加（P＜0.05）,这种蛋白表达产物主要分布在神经元的胞体和轴突.结论 GAP-43在耐药性颞叶癫痫患者脑组织表达增强,提示它们可能参与了耐药性癫痫的形成.     

Effects of ABCB1 polymorphisms on plasma carbamazepine concentrations and pharmacoresistance in Chinese patients with epilepsy

P-glycoprotein may play a role in drug resistance in epilepsy by limiting gastrointestinal absorption and brain access of antiepileptic drugs (AEDs). We sought to investigate the effects of ABCB1 polymorphisms on plasma carbamazepine (CBZ) concentrations and pharmacoresistance in Chinese patients with epilepsy. C1236T, G2677T/A, and C3435T polymorphisms of ABCB1 were genotyped by polymerase chain reaction amplification followed by restriction fragment length polymorphism analysis or direct automated DNA sequencing in 84 patients treated with CBZ monotherapy. Patients with 3435-TT (n=15) had lower adjusted CBZ concentrations than those with 3435-CC (n=30) (P=0.026). However there were no associations between all the studied genotypes, haplotypes, or diplotypes involving ABCB1 C1236T, G2677T/A, and C3435T polymorphisms and pharmacoresistance in the patient cohort. Our results suggest that ABCB1 3435-TT is associated with decreased plasma CBZ levels in Chinese patients with epilepsy. However, whether this contributes to CBZ resistance needs to be further investigated in a larger cohort of patients.     

重症肌无力伴胸腺瘤患者胸腺组织蛋白4.1R mRNA的表达研究

目的探讨蛋白4.1R在重症肌无力(myasthenia gravis,MG)伴胸腺瘤患者胸腺组织中的表达情况。方法运用半定量RT-PCR方法检测7例胸腺瘤MG与7例正常对照组胸腺组织中蛋白4.1R的表达。结果胸腺瘤MG组胸腺组织中蛋白4.1R mRNA的相对表达水平为0.84±0.46,与对照组0.43±3.69相比明显增高,差异有统计学意义(P0.05)。结论蛋白4.1R在胸腺瘤MG患者胸腺组织中mRNA水平表达异常,可能干扰胸腺细胞的信号传导,从而影响胸腺细胞的增殖和活化,参与了MG的发生。     

Association of an ABCB1 gene haplotype with pharmacoresistance in temporal lobe epilepsy

The multidrug transporter P-glycoprotein is suspected of contributing to pharmacoresistance in temporal lobe epilepsy (TLE). To assess the role of functional variations in its coding gene (ABCB1) the authors genotyped 210 patients with TLE who were stratified according to their degree of drug resistance. They identified a common haplotype that when present in the homozygous state significantly increased the risk for pharmacoresistance.     

The oral glucose tolerance test is frequently abnormal in patients with uncontrolled epilepsy

PURPOSE: The clinical efficacy of the ketogenic diet as therapy for patients with difficult-to-treat epilepsy prompted us to investigate the glucose metabolism of these patients under an oral overload of glucose, that is, in the oral glucose tolerance test (OGTT). METHODS: Thirty patients (12 males, 18 females; age range: 17-59, mean: 35.1) with difficult-to-treat epilepsy, 23 patients with controlled epilepsy (11 males, 12 females; age range: 14-66, mean: 36.9), and 39 control subjects (18 males, 21 females; age range: 16-58, mean: 33.3) were evaluated with the OGTT. For patients with epilepsy, we also measured C-peptide and glycosylated hemoglobin in the fasting state. Glucose levels lower than 70 mg/dL at any point of the curve were considered to be abnormal. RESULTS: All subjects in the control group and the group with controlled epilepsy had a normal OGTT. In contrast, all 30 patients with difficult-to-treat epilepsy had at least one point on the OGTT curve below the normal range (P<0.001), most often 180 and 240 minutes after the oral glucose load (P<0.001). C-peptide levels were significantly lower in the group with difficult-to-treat epilepsy as compared with the group with controlled epilepsy. Fasting glycohemoglobin and insulin levels did not differ between the two patient groups. CONCLUSIONS: We suggest that undiagnosed metabolic disturbances in patients with difficult-to-treat epilepsy may somehow contribute to their refractoriness to conventional pharmacological therapy. We propose the hypothesis that calorie-restricted diets aimed at correcting OGTT curves may prove beneficial in treating patients with difficult-to-treat epilepsy. Our hypothesis generates a clear endpoint for the diet, and its demonstration would provide new standards for diet-based antiepileptic regimens. Accordingly, our results may help in understanding the positive consequences of ketogenic or calorie-restricted diets in persons with seizures.     

Aurora-A基因在人脑胶质瘤组织中的表达及意义

目的通过检测人脑胶质瘤患者肿瘤组织中Aurora-A基因的表达水平,探讨Aurora-A基因与胶质瘤的关系。方法采用荧光实时定量逆转录聚合酶链式反应(RT-PCR)法,检测了42例人脑胶质瘤组织和20例正常脑组织中Auro-ra-AmRNA表达水平,分析其表达水平与胶质瘤的关系。结果Aurora-AmRNA在胶质瘤组、Ⅰ-Ⅱ级胶质瘤组、Ⅲ-Ⅳ级胶质瘤组及对照组中的表达量分别为1.414±0.157%、0.380±0.067%、2.050±0.144%、0.040±0.004%。统计显示Aurora-AmRNA表达水平在胶质瘤组明显高于对照组(P0.05),且在Ⅰ-Ⅱ级胶质瘤组及Ⅲ-Ⅳ级胶质瘤组中均明显高于对照组(P0.05),同时Aurora-AmRNA表达水平在Ⅲ-Ⅳ级胶质瘤组中显著高于Ⅰ-Ⅱ级胶质瘤组(P0.05)。结论Aurora-A基因在人脑胶质瘤组织中有高表达,说明Aurora-A基因在胶质瘤的发生、发展过程中起重要作用;Aurora-A基因在Ⅲ-Ⅳ级恶性程度高的胶质瘤组织中有更高表达,说明Aurora-A基因可能与胶质瘤的恶性程度存在密切关系。     

Calcineurin A gamma and B gene expressions in the whole blood in Japanese patients with schizophrenia

Calcineurin (CaN) has been regarded as a candidate gene for vulnerability of schizophrenia. Although CaN gene expression has been investigated with postmortem brain specimens or in association studies, little information is available about CaN gene expression levels in peripheral sources.

We obtained whole blood samples from 16 patients with schizophrenia and 16 controls, and total RNA was extracted. CaN A gamma and CaN B genes were analyzed by quantitative RT-PCR. In the patient group, expression levels of both genes were correlated with psychopathology, as measured by the Brief Psychiatric Rating Scale (BPRS), and neuroleptic dose.

No significant differences in CaN A gamma or CaN B gene expression were observed between patients with schizophrenia and normal controls. Linear regression analysis revealed that the CaN A gamma gene expression level was associated with the BPRS score but not with neuroleptic dose. Neither of the clinical variables was associated with the CaN B gene expression level.

The results of this study suggest that the CaN A gamma gene may be an effective predictor of the progression of psychosis. The effect of medications on expression of CaN genes requires further study.