抗癫痫药物鼻腔给药治疗癫痫发作研究进展

以全身疾病为治疗目的的鼻腔给药具有相对生物利用度高、吸收迅速、起效快、使用方便等特点,而且药物可以绕过血脑屏障、具有一定的脑靶向性,非常适合于癫痫发作的急救、自救治疗。笔者就抗癫痫药物鼻腔给药治疗癫痫发作的研究进展,从药物动力学、药效学、临床应用等方面进行综述。     

细胞色素酶CYP3A4基因多态性研究进展

背景 药物代谢酶的基因多态性是导致药物在体内处置和反应存在明显个体差异的重要因素之一,而细胞色素酶P450家族的CYP3A4 (cytochrome P450 3A4)酶是药物及外源性物质的主要代谢酶.CYP3A4基因多态性是导致这些药物代谢个体差异的主要原因.目的 就CYP3A4基因多态性对药物代谢的影响作一综述.内容 CYP3A4主要分布于肝脏和小肠内,其基因结构、酶活性的个体差异以及遗传多态性的种族差异,是导致药物作用和副作用个体差异的主要原因,甚至与许多疾病包括肿瘤等的发病有关.趋向 对CYP3A4基因多态性的研究将有助于提高药物疗效,避免副作用发生,预防和治疗某些疾病尤其是肿瘤等疾病.     

代谢酶基因多态性与胰腺癌易感性研究进展

代谢酶基因多态性与肿瘤的关系是近来国内外研究的热点。代谢酶基因多态性使酶的活性发生改变,是胰腺癌遗传易感性的重要机制。现综述了与胰腺癌癌变过程中有关的代谢酶基因多态性与其易感性的关系。     

不同抗癫痫药对骨密度影响

本文讨论苯妥英钠，卡马西平，丙戊酸钠三种常用抗癫痫药对骨密度的影响。有文献报导服抗癫痫药会导致骨质疏松，但对以上这三种常用的抗癫痫药那种对骨密度代谢影响最大，还未见报告过。自１９９７年３月至１９９８年７月，我院采用美国ＬＵＮＡＲ双能Ｘ线骨密度仪，对２...     

鱼精蛋白基因多态性与男性不育相关性研究进展

鱼精蛋白(PRM)是精子中含量最丰富的富含精氨酸核蛋白,在精子生成过程中发挥重要作用。在精子发生过程后期PRM取代组蛋白,促使精子中的核基质与核蛋白之间的结合更紧密,从而使核内染色质高度富集、浓缩,防止精子基因组因内部或外部因素而诱发突变。随着DNA测序技术的发展,研究PRM基因多态性与男性生育关系成为一大热点。许多研究表明,PRM1基因rs2301365位点是男性不育的危险因素,会使男性罹患不育的风险增加27%~66%;PRM1基因rs737008位点和PRM2基因rs1646022位点在亚洲人中是男性罹患不育的保护因素;PRM1/PRM2比值也与男性不育存在强相关性。本文综述了PRM基因多态性与男性不育的研究进展。     

脓毒症相关因子基因多态性的研究进展

基因多态性在脓毒症、MODS等炎症反应紊乱相关疾病的病理生理变化中起着重要的作用,基因多态性是决定人体对应激打击和感染的易感性与耐受性、临床表现多样性及药物治疗反应性差异的重要内在因素。近年来的研究发现炎症反应中的一些关键分子的基因多态性在很大程度上确定着患者的命运,现就此方面作一综述     

人类胆石病基因多态性的研究进展

胆固醇结石病（简称胆石病）多发生在胆囊内,是一种多基因遗传病。1999年,Duggirala等使用家谱资料研究墨西哥裔美国人32个家族有症状胆结石的遗传易感性,评估了遗传率为（44±18）％。另一项美国的家族研究分析了358个家族中的1038例,计算出有症状的胆石病的遗传率为（29±14）％。同时胆石病又是环境因素和多种未确定基因复杂的相互作用结果。瑞典进行了一项双胎的研究,     

基因多态性和麻醉

由于基因的多态性，导致不同人群及个体问药物转运蛋白功能的差异、靶受体对相同药物的敏感性差异及药物代谢酶活性的差异，从而对相同药物产生不同的反应。现就基因多惫胜对麻醉药物的转运蛋白、作用受体及代谢酶三方面的影响作一综述。     

基因多态性和麻醉

由于基因的多态性,导致不同人群及个体间药物转运蛋白功能的差异、靶受体对相同药物的敏感性差异及药物代谢酶活性的差异,从而对相同药物产生不同的反应。现就基因多态性对麻醉药物的转运蛋白、作用受体及代谢酶三方面的影响作一综述。     

绝经后骨质疏松症相关基因多态性的研究进展

国内外学者对骨质疏松症的遗传机制已开展了大量的研究,试图寻找与其发生密切相关的致病基因,从而揭示其遗传机制.在复习绝经后骨质疏松症相关文献的基础上,本文对雌激素受体基因、维生素D受体基因及I型胶原基因等相关基因多态性进行综述,发现相关文献报道虽多,但研究结果争议较多,尚不能达成共识.认为骨质疏松症不太可能是由个别基因的主要效应导致,而应该由多个基因分别产生微效应来决定;且已发现的这些基因可能占所有与其相关基因的4%还不到,尚有许多与之相关的基因未被发现及重视.近年来,全基因组关联研究结果以及今后类似的研究已为骨质疏松症的基因学研究开启了一片新天地.     

Predictors of bone density in ambulatory patients on antiepileptic drugs

BACKGROUND AND AIM: Antiepileptic drugs are associated with bone loss and fractures. Data in children is scarce and the impact of new therapies and of low vitamin D is not clear. This study assessed predictors of bone mineral density (BMD) in 225 ambulatory patients with epilepsy. METHODS: BMD and detailed clinical information were obtained from 137 adults mean age of 31 years, on therapy for a mean of 11.7 years, and 88 children mean age of 13 years, on therapy for an average of 4.7 years. RESULTS: Hypovitaminosis D was common in epileptic patients. BMD was reduced in adults but not children with epilepsy, by 0.3-0.6 SD depending on the skeletal site measured, compared to controls. Duration of treatment, but not vitamin D levels, was negatively correlated with BMD at the hip in adults. Bone density was reduced with the use of both enzyme and non-enzyme-inducing drugs, with both mono- and polytherapy, and was most severely reduced at the spine and hip with the use of enzyme-inducing drugs. In the multivariate analyses, polytherapy in children and duration of therapy and enzyme-inducing drugs in adults were independent predictors of BMD. CONCLUSION: Antiepileptic drug therapy is associated with low bone density at clinically relevant skeletal sites, projecting into a possible doubling of fracture risk. Age, therapy duration, polypharmacy and the use of enzyme-inducing drugs were risk factors. Newer drugs may be associated with deleterious effects on bone. Skeletal monitoring with varying intervals, depending on the individual risk profile, is indicated.     

Unilateral multicystic dysplastic kidney in infants exposed to antiepileptic drugs during pregnancy

Prenatal exposure to antiepileptic drugs (AEDs) increases the risk of major congenital malformations (MCM) in the fetus. AED-related abnormalities include heart and neural tube defects, cleft palate, and urogenital abnormalities. Among the various congenital anomalies of the kidney and urinary tract (CAKUT), multicystic dysplastic kidney (MCDK) disease is one of the most severe expressions. Although prenatal ultrasound (US) examination has increased the prenatal diagnosis of MCDK, the pathogenesis is still unclear. We report on four cases of MCDK in infants of epileptic women treated with AEDs during pregnancy. From October 2003 to June 2006, we observed four infants with unilateral MCDK born to epileptic women. Three patients were considered to have typical features of multicystic dysplastic kidney, and one infant was operated because of a cystic pelvic mass in the absence of a kidney in the left flank. The macroscopic appearance of this mass showed an ectopic multicystic kidney confirmed by histological findings. All patients have been studied by US scans, voiding cystourethrogram (VCUG), and radionuclide screening isotope imaging. The prenatal exposure to AEDs increases the risk of major congenital malformations from the background risk of 1–2% to 4–9%. AEDs may determine a defect in apoptosis regulation that could lead to abnormal nephrogenesis, causing MCDK. Carbamazepine (CBZ) and phenobarbital (PHB) during pregnancy should be used at the lowest dosage compatible with maternal disease. The reduction, or even suspension, of drug dosage should be achieved from the periconceptional period to the first 8 weeks of gestation to avoid any interference with organogenesis.     

CYP3A5基因多态性对中国肾移植受者他克莫司血药浓度和疗效的影响

目的研究CYP3A5基因多态性对肾移植受者他克莫司（FK506）血药浓度／剂量比（blood drag concentration／dose,C／D）,术后急性排斥反应（AR）及不良反应发生率的影响。方法采用聚合酶链反应-限制性片段长度多态性技术检测’肾移植受者CYP3A5基因型,并以直接测序法进行验证。比较不同基因型患者之间的FK506C／D值,AR、不良反应的发生率。结果肾移植术后3个月内,＊3／＊3基因型患者FK506的C／D值为149±59,明显高于＊1／＊1基因型和＊1／＊3基因型患者的78±24和90±42（均为P〈0．05）;移植术后3个月内＊1／＊1基因型患者的AR发生率与＊1／＊3基因型和＊3／＊3基因型患者的AR发生率比较差异无统计学意义。＊1／＊1基因型和＊1／＊3基因型患者比较,＊3／＊3基因型患者术后肝功能异常、药物肾毒性不良反应的发生率较高（均为P〈0．05）。结论CYP3A5基因多态性对服用FK506肾移植患者的C／D值、肝功能异常、药物肾毒性有一定影响。CYP3A5＊3／＊3基因型患者的FK506的C／D值、肝功能异常和药物肾毒性不良反应的发生率较高。     

Study on relationship of apolipoprotein E gene polymorphism and genetic susceptibility of stress urinary incontinence

<正>Objective:To explore the relationship between apolipoprotein E(ApoE) gene polymorphism and susceptibility of stress urinary incontinence(SUI). Methods:ApoE genotypes were examined by polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP) technique in 99 patients with SUI and 101 asymptomatic controls. Results:The frequency of allele e3 of ApoE was slightly lower in patients with anatomic SUI than that in controls (79.44%vs.81.68%),while the frequency of allele e4 of ApoE was slightly higher in patients with anatomic SUI than that in controls(10.00%vs.9.90%).No significant difference was found in frequency of allele e3 or e4 between SUI patients and controls(x~2=0.523,P = 0.770). Conclusion:The gene polymorphism of ApoE is not independently involved in the development of SUI.     

复发性流产遗传学病因学研究进展

复发性流产(RSA)是常见的人类生殖疾病,目前对于其病因的研究主要集中在遗传、免疫、血栓前状态、内分泌和解剖等方面,但仍有一部分不明原因的RSA不能确定为上述病因。因此,本文从染色体异常、基因多态性及基因突变、精子DNA完整性等方面对RSA遗传学病因的研究现状进行综述。     

抗骨质疏松药物对骨质疏松症患者糖代谢、脂代谢的影响

骨质疏松症与心血管疾病已成为影响中老年人健康与生活质量的重要原因。研究发现糖代谢、脂代谢可以与骨代谢相互影响,而糖脂代谢异常可致心血管风险增高。目前现有研究发现抗骨质疏松药物可以影响心血管事件的发生,但关于其风险因素的研究却较少。因此,本文拟通过综述抗骨质疏松药物对患者糖代谢、脂代谢的影响,探讨抗骨质疏松药物非骨骼方面的益处和危害,使患者在控制骨折风险的同时,对心血管疾病进行管理,从而改善患者的整体状况。     

The molecular genetics of blood group polymorphism

Nearly 300 blood group specificities on red cells are known, many of which are polymorphic. The molecular mechanisms responsible for these polymorphisms are diverse, though the majority represent single nucleotide polymorphisms (SNPs) encoding amino acid substitutions. Other mechanisms include the following: gene deletion; single nucleotide deletion and sequence duplication, which introduce reading-frame shifts; nonsense mutation; intergenic recombination between closely-linked genes, giving rise to hybrid genes and hybrid proteins; and a SNP in the promoter region of a blood group gene. Examples of these genetic mechanisms are taken from the ABO, Rh, Kell, and Duffy blood group systems. Null phenotypes, in which no antigens of a blood group system are expressed, are not generally polymorphic, but provide good examples of the effect of inactivating mutations on blood group expression. As natural human 'knock-outs' they provide useful clues to the functions of blood group antigens. Knowledge of the molecular bases to blood group polymorphisms provides a means to predict blood group phenotype from genomic DNA with a high degree of accuracy. This currently has two main applications in transfusion medicine: for determining fetal blood groups to assess whether the fetus is at risk from haemolytic disease; and to determine blood group phenotypes in multiply transfused, transfusion-dependent patients, where serological tests are precluded by the presence of donor red cells. Other applications are being developed for the future.