中枢类大麻受体拮抗剂利莫那班对2型糖尿病周围神经病变疗效的实验分析

目的 观察利莫那班对大鼠糖尿病周围神经痛变的疗效,探讨其作用机制.方法 采用链尿佐菌素(STZ)腹腔注射诱导形成糖尿病周围神经病变(DPN)模型,随机分为模型对照组、利莫那班小剂量组、利莫那班大剂量组、正常对照组.糖尿病大鼠造模成功后予利莫那班干预,开始给药24周后将模型组和正常组比较痛阈、坐骨神经传导速度.用酶联免疫吸附测定法(ELISA法)分别洲定各组大鼠血清、脊髓及坐骨神经内IL-Iβ、TNF-α的浓度.结果 利莫邢班对DNP大鼠痛阈、坐骨神经传导速度(NCV)有明显改善(P＜0.05).与对照组比较.DPN模型组大鼠的lL-Iβ、TNF-α的含量显著增高(P＜0.05),利莫那班治疗24周后.与DPN模型组比较IL-lβ、TNF-α的含量显著降低(P＜0.05).结论 利莫那班对糖尿病周围神经病变有良好的疗效,可能是通过调节自身免疫功能机制发挥作用.     

早期高压氧治疗对慢性压迫性损伤模型大鼠疼痛行为学的影响

目的观察神经病理性疼痛发病早期0.25 MPa高压氧治疗对大鼠疼痛行为学的影响,并探讨早期治疗的作用机制。方法采用左后肢坐骨神经结扎术建立慢性压迫性损伤大鼠模型,术后早期(第1天)即开始进行高压氧(0.25 MPa)治疗(60 min/d),5d后观察大鼠一般情况、自发缩足次数、缩足阈值(PWT)和缩足潜伏期(PWL)等疼痛行为学变化。结果与假手术组相比,模型组大鼠体质量显著下降(t=4.772,P=0.000)、高压氧组大鼠体质量降低幅度小于模型组(t=2.411,P=0.029);模型组大鼠术后即出现缩足潜伏期缩短(t=28.345,P=0.000),第3天开始自发缩足次数增多(t=12.541,P=0.000)、缩足阈值降低(t=4.032,P=0.001)。与模型组相比,高压氧治疗组大鼠术后第3天开始缩足次数减少(t=8.077,P=0.000)、缩足阈值增加(t=2.114,P=0.049)、缩足潜伏期延长(t=7.715,P=0.000)。结论早期施行高压氧(0.25 MPa)治疗可以显著改善神经病理性疼痛大鼠痛敏症状,为临床神经病理性疼痛提供一种新的便捷、经济、有效的治疗方法。     

不同剂量神经生长因子对神经源性疼痛大鼠脊髓Fos蛋白的影响

背景：神经生长因子对神经元的存活、生长发育、分化、再生和功能维持起到调控作用。 目的：进一步验证不同剂量神经生长因子对神经源性痛大鼠的治疗作用以及对脊髓中Fos蛋白的影响。 设计、地点：随机对照动物实验，在上海第九人民医院完成。 材料：健康成年雄性Wistar大鼠72只,体质量180~200 g，随机分为4组，模型组及腹腔注射神经生长因子4， 8，16 μg组，每组18只。 方法：72只大鼠结扎左侧坐骨神经制备坐骨神经慢性缩窄性损伤模型；腹腔注射神经生长因子4， 8，16 μg组，造模后分别腹腔注射神经生长因子4，8，16 μg/(kg•d)。 主要观察指标：①于术前和术后第1，2，3，5，7，10，14天进行行为学观察和机械性痛阈测定。②于术后第2，7，14天各组分别处死大鼠各6只，取脊髓，应用免疫组织化学方法和图像分析系统检测脊髓中Fos蛋白的表达。 结果：模型组大鼠术后出现自发抬足、舔足等自发痛表现，术后第3天起开始出现痛阈下降，第14天达最低值，而注射神经生长因子组大鼠没有自发痛表现，没有出现机械性痛阈的低常期，第10，14天模型组大鼠痛阈与其余各组比较差异有显著性意义(P < 0.05)。4组大鼠术后第1天机械性痛阈普遍升高；注射神经生长因子16 μg组大鼠术后第1天机械性痛阈比其他各组低(P < 0.01)，第2天机械性痛阈恢复至术前水平，低于注射神经生长因子4 μg组(P < 0.05)。术后模型组大鼠脊髓Fos蛋白表达进行性升高，而其他各组大鼠脊髓中仅有少量Fos阳性神经元，模型组与其余各组比较差异显著(P < 0.01)。术后第2天注射神经生长因子16 μg组大鼠脊髓Fos蛋白表达最低，与模型组和注射神经生长因子4 μg组比较，差异有显著性意义(P < 0.01)。 结论：神经生长因子对大鼠神经源性痛有治疗作用，且大剂量较小剂量作用更为明显，其机制可能与抑制脊髓中Fos蛋白表达有关。     

制何首乌提取物对创伤后应激障碍大鼠的神经保护作用及其机制

目的 研究制何首乌提取物对创伤后应激障碍(PTSD)大鼠神经保护作用及其机制。方法60只雄性SD大鼠随机分为5组,每组各12只。对照组大鼠常规饲养; PTSD模型组大鼠以幽闭电击法建立PTSD模型;低、中、高剂量制何首乌组大鼠造模后分别予以0. 5、1. 5、3 g/kg制何首乌提取物腹腔注射。比较各组大鼠的Morris水迷宫(MWM)评分、神经损伤严重缺损评分(NSS)、旷场试验(FT)、高架十字试验(ECT)结果、海马区细胞形态学、海马区神经元细胞凋亡灰度值、核因子Kappa B/抑制蛋白(NF-κB/IκB)通路p65、p IκBα/IκBα表达水平。并在给药大鼠中挑选改善效果最好的剂量组,给予NF-κB激活剂CHPG,观察其对海马区神经元凋亡的影响。结果 高、中、低剂量组大鼠逃避潜伏期、NSS评分低于PTSD模型组,穿越平台位置次数、在原平台所在象限的时间占比、中央进入次数、水平活动度、开臂停留时间、开臂进入次数高于PTSD模型组。并且3组中剂量越高组大鼠以上指标改善越明显(均P 0. 05)。PTSD模型组大鼠海马细胞排列疏松、胞浆染色深浅不一、细胞数目减少、体积缩小,存在固缩、变性神经元。低、中、高剂量组较模型组依次改善;高、中、低剂量组大鼠海马区细胞凋亡灰度值低于PTSD模型组;并且3组中剂量越高组大鼠的海马区细胞凋亡灰度值越低(均P 0. 05)。高、中、低剂量组p65、p IκBα/IκBα低于PTSD模型组,且3组中剂量越高组的p65、p IκBα/IκBα表达降低幅度越大(均P 0. 05)。应用CHPG大鼠海马区细胞凋亡灰度值显著高于未应用CHPG大鼠(均P 0. 05)。结论 制何首乌提取物可改善PTSD大鼠行为学和海马区损害,并能呈剂量依赖性靶向NF-κB/IκB通路调控海马区神经元凋亡。     

核因子-κB对癫痫大鼠脑 P-糖蛋白表达的调控作用

目的 探讨核因子-κB(NF-κB)对癫痫大鼠脑P-糖蛋白(P-gP)表达的影响.方法 将雄性SD大鼠随机分为假手术组(n=9)、癫痫组(EP组,n=14)、NF-κB活性抑制剂吡咯烷二硫代氨基甲酸盐(PDTC)干预组(PDTC组,n=14).采用大鼠海马注射海人酸方法制作癫痫模型,PDTC组于癫痫造模前30 min给予腹腔注射PDTC(按体质量150 mg/kg).于造模后24 h处死各组大鼠,采用免疫组织化学方法检测并比较各组大鼠海马CA3区、齿状回、嗅周皮层、杏仁核复合体区P-gp和NF-κB亚基p65(NF-κBp65)表达情况.结果 与假手术组相比,EP组海马CA3区、齿状回、杏仁核复合体区P-gP和NF-κBp65表达显著增强(PO.05).结论 抑制NF-κB活化可以降低癫痫相关脑区P-gp过表达,癫痫发作所致脑内P-gp表达上调可能与NF-κB活化有关.     

神经减压缓解糖尿病大鼠触诱发痛的机制研究

目的探讨周围神经减压术缓解糖尿病大鼠触诱发痛的机制。方法将健康成年雄性SD大鼠按随机数字表法分为5组,分别为Ⅰ组(正常对照,n=10)、Ⅱ组(糖尿病模型,n=20)、Ⅲ组(糖尿病模型+乳胶管置入,n=10)、Ⅳ组(糖尿病模型+乳胶管置入+神经减压,n=10)及Ⅴ组(糖尿病模型+乳胶管置入+单纯术区显露,n=10)。糖尿病模型采用链脲佐菌素(STZ)腹腔注射,神经减压法即去除坐骨神经乳胶管。建模后3 d,采用up-down法检测各组大鼠的缩足阈值,保留Ⅱ~Ⅴ组中出现触诱发痛的大鼠。采用透射电镜观察5组大鼠坐骨神经的形态,分别对有髓和无髓神经纤维进行测量。进一步采用蛋白质免疫印迹(WB)和免疫荧光实验对5组大鼠脊髓后角γ-氨基丁酸B型(GABAB)受体的表达进行定量和定位检测。结果术后3周,STZ注射结合乳胶管置入(Ⅲ、Ⅳ、Ⅴ组)较单纯性STZ注射(Ⅱ组)大鼠触诱发痛的发生率高[分别为86.7%(26/30)、55.0%(11/20),χ^2=6.254,P=0.012]。Ⅱ、Ⅲ、Ⅳ、Ⅴ组的缩足阈值[分别为(4.06±1.28)g、(3.09±1.43)g、(4.02±1.96)g、(4.15±1.87)g]均低于Ⅰ组[(13.41±1.88)g,均P<0.05];术后5周,Ⅳ组的缩足阈值高于Ⅱ、Ⅲ、Ⅴ组(均P<0.05)。电镜观察结果显示,Ⅱ、Ⅲ、Ⅳ、Ⅴ组有髓和无髓神经纤维的面积、密度均较Ⅰ组减小(均P<0.05),有髓神经纤维的g比例较Ⅰ组增加(均P<0.05);Ⅳ组有髓纤维的面积和密度均大于Ⅱ、Ⅴ组(均P<0.05)、g比例低于Ⅱ、Ⅴ组(均P<0.05)。WB结果显示,神经减压术后3周,Ⅱ、Ⅲ、Ⅳ、Ⅴ组GABAB受体的表达量均较Ⅰ组下降(均P<0.05),而Ⅳ组高于Ⅴ组(P<0.05)。免疫荧光结果显示,Ⅱ、Ⅲ、Ⅳ、Ⅴ组中GABAB受体在脊髓背角内神经丝蛋白(NF)-200+区和NF-200+神经元的表达均较Ⅰ组下调(均P<0.05)。结论周围神经减压术可缓解糖尿病大鼠触诱发痛,主要通过去除有髓神经纤维的压迫、解除GABAB受体下调介导的中枢敏化,从而恢复脊髓兴奋性升高的病理状态。     

氯胺酮对糖尿病周围神经病变大鼠脊髓TNF-α表达的影响

目的探讨氯胺酮对糖尿病周围神经病变大鼠的脊髓保护作用。方法成年雌性W istar大鼠70只,随机留取10只为正常对照组(A组),腹腔注射生理盐水(3 m.lkg-1.d-1);其余大鼠用链脲菌素(STZ)制造糖尿病模型,得到48只糖尿病大鼠。将其随机等分为2组:B组为糖尿病对照组(n=24):腹腔注射与A组等体积的生理盐水;C组为氯胺酮治疗组(n=24):腹腔注射氯胺酮10 m.gkg-1(1 m.gm l-1);于治疗后第1、3、5及8周分别进行行为学测定,记录机械痛觉;于第8周测定并记录神经传导速度;取脊髓切片,应用免疫组化方法和图象分析系统检测TNFα-在脊髓背角的表达情况,同时用尼氏染色法观察脊髓的病理形态学改变。结果与A组比较,B组、C组大鼠脊髓背角组织中TNF-a的表达显著升高(P<0.01);与B组比较,C组的TNFα-表达显著降低(P<0.01),并且减轻了糖尿病慢性神经触诱发痛(P<0.01)。结论糖尿病大鼠周围神经病变引起的神经痛与脊髓背角促炎性细胞因子TNFα-有关。而氯胺酮可明显抑制脊髓背角TNFα-的表达,减轻糖尿病神经痛。     

人睫状肌细胞核因子κB在曲伏前列腺素作用下的变化

背景：核因子κB可能与葡萄膜巩膜房水流出通道的多种细胞信号调控有关。 目的：观察前列腺素类曲伏前列腺素药物作用下，体外培养的人睫状肌细胞核因子кB及其抑制因子（inhibitor，IκB）的变化。 设计、时间及地点：对比观察实验，于2005-03/2006-11在中山眼科中心实验室完成。 材料：供体取自中山眼科医院，摘自死亡 1 h内无眼疾青年尸体眼球。患者家属对实验知情同意，并自愿捐献。 方法：在人睫状肌细胞培养基中加1 μmol/L曲伏前列腺素，根据孵育时间的不同分为4组，即0 h对照组和6，12，24 h组。 主要观察指标：采用real-time RT-PCR、免疫荧光半定量分析和ELISA法分别检测上述时间组核因子κB p65、ⅠκBα在基因和蛋白水平的表达。 结果：①与对照组比较，6，12，24 h组 核因子κB p65 mRNA表达均下降(F= 17.068,P=0.001);IκBαmRNA 6 h组、12 h组较对照组改变不明显(P > 0.05)，24 h组较对照组表达增加(F=32.742，P=0.000)。②免疫荧光半定量分析表明：核因子κB p65荧光强度6，12，24 h组均较对照组减少(F=17.216，P=0.000);IκBα6 h组较对照组没有明显改变(P=0.134)、12 h组较对照组轻微下降(P=0.032)，24 h组较对照组明显增加(F=17.346，P=0.001)。③ELISA法检测磷酸化核因子κB p65随药物作用时间延长而逐渐下降(F=15.4，P=0.001)。 结论：曲伏前列腺素作用于人睫状肌细胞后，核因子κB p65的基因表达下调，核易位抑制，IκBα的基因表达上调。     

正清风痛宁对偏头痛大鼠脑干IL-1β、TNF-α表达的影响

目的观察正清风痛宁对炎性细胞因子白介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)在偏头痛大鼠脑干表达的影响。方法将60只Wistar大鼠(雌雄各半)随机分为空白对照组(空白组)、偏头痛模型组(模型组)、舒马普坦组及正清风痛宁高、中、低剂量干预组(高、中、低剂量组)共6组。除空白组外,其余5组大鼠均建立三酰甘油偏头痛模型,用免疫组化SP法测定各组大鼠脑干IL-1β、TNF-α阳性细胞数。结果 6组大鼠间IL-1β、TNF-α阳性细胞数比较差异有统计学意义(分别F=7.063,P=0.001;F=8.257,P=0.000);组间两两比较,模型组脑干IL-1β(18.9±8.17)、TNF-α(14.30±6.41)阳性细胞数较空白组(5.90±2.69、5.00±1.63)增多(分别t=-4.780、P=0.000,t=-4.444,P=0.000),舒马普坦组(2.80±2.15,t=6.026,P=0.000;0.00±0.00,t=7.052,P=0.000)、中剂量组(7.70±4.76,t=3.745,P=0.000;6.20±1.99,t=3.815,P=0.000)、高剂量组(7.80±5.90,t=3.482,P=0.003;5.90±2.88,t=3.778,P=0.001)IL-1β、TNF-α阳性细胞数均较模型组减少;低剂量组脑干IL-1β(13.5±4.30,t=1.849,P=0.081)、TNF-α(11.30±6.11,t=1.071,P=0.298)阳性细胞数与模型组比较差异均无统计学意义;与舒马普坦组比较,低剂量组(t=-7.037,P=0.000;t=-5.847,P=0.000)、中剂量组(t=-2.966,P=0.011;t=-9.858,P=0.000)、高剂量组(t=-2.517,P=0.022;t=-6.467,P=0.000)脑干IL-1β、TNF-α阳性细胞数均增多;与低剂量组比较,中(t=-2.858,P=0.011;t=-2.510,P=0.022)、高剂量组(t=-2.468,P=0.024;t=-2.527,P=0.021)脑干IL-1β、TNF-α阳性细胞数减少;中、高剂量组脑干IL-1β、TNF-α阳性细胞数差异无统计学意义(t=0.042,P=0.967;t=-0.271,P=0.790)。结论正清风痛宁可能抑制偏头痛大鼠炎性细胞因子IL-1β、TNF-α的表达。     

异氟烷预处理对偏头痛大鼠行为学症状及三叉神经节相关蛋白表达的影响

目的探讨异氟烷(ISO)对硝酸甘油所致偏头痛大鼠行为学症状及三叉神经节内相关蛋白表达的影响。方法采用随机数字表法将SD大鼠分为对照组(S组)、模型组(M组)、ISO预处理组(包括低剂量和高剂量组,即L组和H组),每组10只,并采用皮下注射硝酸甘油法制备偏头痛模型。L组和H组于造模前30 min分别给予1%和2%ISO吸入麻醉30 min。观察并比较各组大鼠造模后耳红出现和消失的时间及每30 min时间(T_(1-7))段内的挠头、爬笼次数。采用Western blot测定三叉神经节内白介素-1β(IL-1β)、环氧合酶-2(COX2)、降钙素基因相关肽(CGRP)及核转录因子-κB p65(NF-κB p65)的蛋白表达水平。结果与S组相比,M组和ISO预处理组大鼠造模后均出现双耳发红及挠头、爬笼次数均增多等现象,三叉神经节内IL-1β、COX-2、CGRP及胞核NF-κB p65蛋白表达水平明显升高,胞浆NF-κB p65蛋白表达水平明显降低(P 0. 05);与M组相比,ISO预处理组大鼠耳红消失的时间明显缩短,T_(2-7)时挠头次数均明显减少,T_(2-6)时爬笼次数均明显减少,三叉神经节内IL-1β、COX-2、CGRP及胞核NF-κB p65蛋白表达水平明显降低,胞浆NF-κB p65蛋白表达水平明显升高(P 0. 05),且H组较L组更明显(除胞浆NF-κB p65蛋白外)。结论异氟烷能改善偏头痛大鼠的行为学症状,其机制可能与下调三叉神经节内IL-1β、COX-2、CGRP蛋白的表达水平及抑制NF-κB的激活有关。     

Epilepsy and anomalies of neuronal migration: MRI and clinical aspects

Neuronal migration disorders are the result of disturbed brain development. In such disorders, neurons are abnormally located. In diagnosing these conditions, magnetic resonance imaging is superior to any other imaging technique. This enables us to improve our knowledge of the clinical correlates of neuronal migration. With reference to migrational disorder, a retrospective study of all 303 patients with epileptic seizures referred for magnetic resonance imaging during a 3-year period was performed, 13 patients (aged 12-41, mean age 27) were identified. They represent 4.3% of the entire study group. Of the patients with known epilepsy, 6.7% and of the mentally retarded, 13.7% had migrational disorders. Four patients had schizencephaly as the dominant finding, one was classified as hemimegalencephaly, 2 had isolated heterotopias, and 6 had localized pachy- and/or poly-microgyria. The clinical pictures are complex. Ectopias of grey matter are recognised foci of epilepsy, but from an epileptological and a clinical viewpoint little attention has been given to these disorders. The present study shows that malmigration is not rare in epilepsy patients, especially not in the mentally retarded.     

Classification of methods in transcranial Electrical Stimulation (tES) and evolving strategy from historical approaches to contemporary innovations

Transcranial Electrical Stimulation (tES) encompasses all methods of non-invasive current application to the brain used in research and clinical practice. We present the first comprehensive and technical review, explaining the evolution of tES in both terminology and dosage over the past 100 years of research to present day. Current transcranial Pulsed Current Stimulation (tPCS) approaches such as Cranial Electrotherapy Stimulation (CES) descended from Electrosleep (ES) through Cranial Electro-stimulation Therapy (CET), Transcerebral Electrotherapy (TCET), and NeuroElectric Therapy (NET) while others like Transcutaneous Cranial Electrical Stimulation (TCES) descended from Electroanesthesia (EA) through Limoge, and Interferential Stimulation. Prior to a contemporary resurgence in interest, variations of transcranial Direct Current Stimulation were explored intermittently, including Polarizing current, Galvanic Vestibular Stimulation (GVS), and Transcranial Micropolarization. The development of these approaches alongside Electroconvulsive Therapy (ECT) and pharmacological developments are considered. Both the roots and unique features of contemporary approaches such as transcranial Alternating Current Stimulation (tACS) and transcranial Random Noise Stimulation (tRNS) are discussed. Trends and incremental developments in electrode montage and waveform spanning decades are presented leading to the present day. Commercial devices, seminal conferences, and regulatory decisions are noted. We conclude with six rules on how increasing medical and technological sophistication may now be leveraged for broader success and adoption of tES.     

Hepatic Considerations in the Use of Antiepileptic Drugs

Summary: Virtually all of the major antiepileptic drugs (AEDs) can cause hepatotoxicity, although fatal hepatic reactions are rare. The mechanisms, incidences, and risk profiles for such reactions differ from drug to drug. With carbamazepine and phenytoin, hepatotoxicity may be due to drug hypersensitivity. Although the profiles of patients at risk have not been well-defined for these two antiepileptic drugs, it would appear from reports in the literature that older adolescents and adults are at higher risk than children of developing serious or fatal hepatotoxicity. Once hepatotoxicity develops, mortality rates are 10–38% with phenytoin and 25% for carbamazepine. The risk profile for valproate fatal hepatotoxicity has been more clearly defined. Those at primary risk of fatal hepatic dysfunction are children under the age of 2 years who are receiving multiple anticonvulsants and also have significant medical problems in addition to severe epilepsy. The risk is considerably lower for patients over the age of 2 years on valproate monotherapy. In contrast to the risk profile with other AEDs, adults receiving valproate as monotherapy have the lowest risk of hepatotoxicity. Fatal hepatic dysfunction coincident with valproate may be the result of aberrant drug metabolism. Concomitant use of AEDs that induce microsomal P450 enzymes (e.g., phenytoin and phenobarbital) may enhance the production of a toxic metabolite, and hence the greater risk of hepatotoxicity with polypharmacy.     

Vascular Malformations and Epilepsy: Clinical Considerations and Basic Mechanisms

Summary: Vascular malformations (VMs) are associated with epilepsy. The natural history of the various VMs, clinical presentation, and tendency to provoke epilepsy determine treatment strategies. Investigations have probed the mechanisms of epileptogenesis associated with these lesions. Electrophysiologic changes are associated with epileptogenic cortex adjacent to VMs. Putative pathophysiologic mechanisms of epileptogenesis include neuronal cell loss, glial proliferation and abnormal glial physiology, altered neurotransmitter levels, free radical formation, and aberrant second messenger physiology.     

Neonatal Seizures: Problems in Diagnosis and Classification

Summary: The clinical identification of neonatal seizures is critical for the recognition of brain dysfunction; however, diagnosis is often difficult because of the poorly organized and varied nature of these behaviors. Current classification systems are limited in their ability to communicate motor, autonomic, and electroencephalo-graphic features of seizures precisely and to provide a basis for uniform effective diagnosis, therapy, and determination of prognosis. Recent investigations of neonates, utilizing bedside electroencephalographic/polygraphic/ video monitoring techniques, have provided the basis for improved diagnosis and classification of seizures in the newborn. These studies have demonstrated that not all clinical phenomena currently considered to be seizures require electrocortical epileptiform activity for their initiation or elaboration. In addition, the specific clinical character of the phenomena considered to be seizures, the clinical state of the infant, and the character of the EEG indicate the probable pathophysiological mechanisms involved and suggest probable etiologies, prognosis, and therapy. Similarities between animal models that demonstrate reflex physiology and neonates with motor automatisms and tonic posturing suggest that these clinical behaviors may not be epileptic in origin but, rather, primitive movements of progression and posture mediated by brainstem mechanisms. Although not all clinical behaviors currently considered to be neonatal seizures may have similar pathophysiological mechanisms, they are clinically significant because they all indicate brain dysfunction.     

Valproate Monotherapy in the Management of Generalized and Partial Seizures

Summary: For decades, therapeutic tradition has promoted the concept of polypharmacy in the management of epilepsy. In recent years, however, studies have shown that, for most patients, monotherapy can provide comparable or better seizure control than administration of multiple anticonvulsants, while diminishing the potential for adverse reactions, drug interactions, and poor compliance. Valproate is an important monotherapeutic agent that is highly effective in the control of idiopathic primary and secondarily generalized epilepsies, and partial seizures that do not generalize. Comparative studies have found that valproate is at least as effective as phenytoin and carbamazepine in the treatment of generalized and partial seizures. Given the similar efficacy, other factors such as pharmacokinetics and side effects may therefore determine anticonvulsant selection for monotherapy.     

Carbamazepine Efficacy and Utilization in Children

Summary: Carbamazepine is effective for preventing partial and generalized tonic-clonic seizures in children. Although absence epilepsies are more common in children than adults, an estimated 80% of children with epilepsy have seizure types or epilepsies that are potentially responsive to carbamazepine. The differential diagnosis of ictal staring is an especially important issue in children because absence and atypical absence seizures are more prevalent in children than adults. Age-related pharmacokinetic differences and drug interactions are major considerations in children. On average, children have higher clearance rates of carbamazepine, shorter half-lives, and higher ratios of carbamazepine-10, 11-epoxide to carbamazepine than adults. In addition, children with severe epilepsy are more likely to require multiple-drug therapy, which can lead to complex drug interactions. When carbamazepine is administered along with valproate, drug protein binding interactions can cause intermittent side effects.     

Un nouveau cadre conceptuel de travail pour la psychiatrie

In an attempt to place psychiatric thinking and the training of future psychiatrists more centrally into the context of modern biology, the author outlines the beginnings of a new intellectual framework for psychiatry that derives from current biological thinking about the relationship of mind to brain. The purpose of this framework is twofold. First, it is designed to emphasize that the professional requirements for future psychiatrists will demand a greater knowledge of the structure and functioning of the brain than is currently available in most training programs. Second, it is designed to illustrate that the unique domain which psychiatry occupies within academic medicine, the analysis of the interaction between social and biological determinants of behavior, can best be studied by also having a full understanding of the biological components of behavior.     

Special Pharmacokinetic Considerations in Children

Summary: Pediatric patients have greater degrees of pharmacokinetic variability and unpredictability than adults. This variability results from the effects of pharmacogenetics, age and growth, prior and current comedication, and disease. Newborns with seizures have the least predictable dosage requirements, and their needs change as drug-eliminating mechanisms mature in the neonatal period. Infants have the highest relative capacities to eliminate antiepileptics of any age group and require the largest relative doses. In addition to age-related trends, children demonstrate the same drug-specific, pharmacokinetic phenomena that adults do, including nonlinear phenytoin elimination, nonlinear valproate binding, and autoinduction of carbamazepine. Intercurrent illness and drug interactions further modify the age-related pharmacokinetic patterns in children and make dosage requirements even more unpredictable. Recent studies have shown that febrile illness can affect drug elimination, sometimes decreasing drug levels by 50% or more. Intermittent treatment with benzodiazepines administered either orally or rectally can be an important adjunct and help minimize this type of problem for children with marginally controlled epilepsy. Intermittent benzodiazepines are also helpful for children who have febrile seizures and who need only occasional antiepileptic protection.