真空冷冻干燥过程中猪主动脉血管的力学性能

摘要 背景：以往的冷冻干燥研究着重探讨冷冻保护剂、降温速率、保存温度等因素，目前尚缺乏冷冻干燥工艺对冻干后血管力学性能的研究。 目的：使用质构仪对冻干后复水的猪主动脉与新鲜猪主动脉进行力学性能对比分析，揭示冷冻干燥过程对猪动脉血管力学性能的影响，从而选择一个适合血管冷冻干燥过程的控制参数。 方法：采用真空冷冻干燥技术，对新鲜的猪主动脉血管进行冻干处理，猪主动脉经过微机控制程序降温仪进行预冻处理，然后由真空冷冻干燥机完成一次和二次干燥过程。冷冻干燥结束后，将冻干血管进行复水，然后使用质构仪对其穿刺应力、轴向拉伸应力和周向拉伸应力进行测量。 结果与结论：血管冷冻干燥合适的预冻速率为1 K/min，一次干燥温度为-20 ℃，二次干燥温度为10 ℃。血管冻干后复水，其力学性能同新鲜血管相比，穿刺和周向拉伸应力分别增大20%和30%左右，轴向拉伸应力减小约20%。结果表明冻干复水后的血管基本保持了新鲜血管的弹性，耐压性和顺应性，可望成为一种有效的血管保存手段。     

鬼臼毒素固体脂质纳米粒冻干粉的制备及理化性质考察*★

目的：制备含有不同冻干保护剂的鬼臼毒素固体脂质纳米粒(POD-SLN)冻干粉，并考察其理化性质，筛选出最佳配方。 方法：实验于2006-12/2007-11在南方医科大学药学部实验室完成。冻干配方为15%海藻糖、15％甘露醇和二者联用各取 5％，冷冻干燥制作冻干粉制剂。扫描电镜下观察冻干粉复溶后粒子形态，Image -Pro Plus 6.0软件计算粒径大小，高效液相考察固体脂质纳米粒的药物包封率，并考察冻干粉的外观、复溶和4 ℃保存对其影响，评价不同辅料对冻干品的影响。 结果：①外观和复溶情况：海藻糖冻干粉、海藻糖联用甘露醇冻干粉表面均松脆多孔，疏松，复溶较快，约需20 s，甘露醇冻干粉表面较光滑，结构致密，饼状，复溶较慢，需借助外力。冻干粉样品4 ℃冰箱放置24 h、1，3，6个月其外观和复溶均无明显变化。②电镜下粒子形态：呈圆形或椭圆形，分布较均匀，冻干前后无明显差异。③粒径：未加冻干保护剂时为（82.65± 18.43）nm，加入海藻糖、海藻糖联用甘露醇、甘露醇后分别为（94.78±21.94），（109.26±16.15），（114.63±21.42）nm。④包封率：未加冻干保护剂时为 87.4%，加入海藻糖、海藻糖联用甘露醇、甘露醇后分别为86.2%，80.3%，79.6%。 结论：以15%海藻糖为冻干保护剂制备的鬼臼毒素固体脂质纳米粒冻干粉粒径较小，包封率高，稳定性好，其制备工艺合理可行。     

低糖对星形胶质细胞水通道蛋白4表达及分布的影响

目的探讨低糖体外培养对大鼠原代星形胶质细胞水通道蛋白4(aquaporin 4,AQP4)表达量及分布的影响。方法对体外培养的原代大鼠星形胶质细胞进行0mmol/L(无糖)和1mmol/L葡萄糖低糖培养,以5.5mmol/L葡萄糖作为正常糖浓度对照进行如下实验:(1)采用活细胞成像技术检测无糖培养后的星形胶质细胞的体积变化;(2)以Western blot检测无糖培养0h、3h、6h、12h和24h,以及0mmol/L、1mmol/L和5.5mmol/L葡萄糖培养24h后星形胶质细胞的AQP4表达量;(3)以免疫荧光染色检测0mmol/L、1mmol/L和5.5mmol/L葡萄糖培养6h后AQP4在星形胶质细胞上的分布。结果 (1)与0min时比较,无糖培养15min(1.14±0.03)和30min时(1.15±0.02)星形胶质细胞相对体积均明显增大(P0.01)。(2)无糖0mmol/L(含血清)培养实验中,与0h(AQP4相对表达量为1)比较,12h(1.55±0.21)、24h时(1.67±0.16)AQP4相对表达量均明显增加(P0.01);0mmol/L、1mmol/L和5.5mmol/L葡萄糖(含血清)培养24h后,与5.5mmol/L组(AQP4相对表达量为1)比较,0mmol/L组AQP4相对表达量(3.23±0.23)明显增加(P0.01)。(3)与0h时(AQP4相对表达量为1)比较,无糖(无血清)培养6h后AQP4蛋白相对表达量(1.32±0.09)明显上调(P0.05),24h时相对表达量(0.80±0.05)下降(P0.05);0mmol/L、1mmol/L和5.5mmol/L葡萄糖(无血清)培养24h后,与5.5mmol/L(AQP4相对表达量为1)组比较,0mmol/L组AQP4相对表达量(0.75±0.07)明显降低(P0.05)。无论含或不含血清,与5.5mmol/L葡萄糖组比较,0mmol/L和1mmol/L组AQP4在星形胶质细胞向膜上集中特异性分布更加明显。结论低糖处理可引起星形胶质细胞水肿,AQP4蛋白表达量发生变化和向细胞膜上集中分布。AQP4在低血糖性脑水肿中可能发挥重要作用。     

工艺因素对冻干骨浸泡掺锶的影响

摘要 背景：冻干骨是临床上常用的自体骨替代材料,在冻干骨中掺入成骨活性元素锶将有助于冻干骨在临床上发挥更大的作用。 目的：观察含锶溶液浓度和处理时间对冻干骨浸泡掺锶的影响,并对锶离子的缓释特征进行观察。 方法：采用5~40 mmol/L的氯化锶溶液处理冻干骨,并对其中浓度10 mmol/L组分别在浸泡1.5,3,6,9 d进行检测,观察在不同时间内锶元素的掺入效率;在去离子水中进行锶离子的缓释效果评价。用ICP-OES等离子体发射光谱仪对元素含量进行分析。 结果与结论：随溶液浓度升高锶元素的掺入量增加,浓度在2.0%~5.1%范围。在所观察的9 d时间内,锶掺入浓度随浸泡时间延长持续增加。锶元素在初期存在爆释效应,之后进入较平稳的释放阶段。30 d内锶离子释放量始终高于松质骨中的钙离子释放量。提示在实验观察的范围内,采用较高含锶浓度溶液以及延长浸泡时间可以提高锶元素在冻干骨中的掺入量。掺锶冻干骨具有长期释放锶离子的能力。     

高浓度腺苷对脑缺血再灌注线粒体编码基因表达影响途径

目的:根据高浓度外源ATP对脑缺血再灌注线粒体编码基因表达具有影响这一研究结果,应用可能作用途径的拮抗剂对其作用途径进行研究。方法:采用颈动脉分流法制备大鼠脑缺血再灌注模型,将缺血时间设置为5分钟,再灌注时间为2小时。采用Fernandez-Silva的细胞器体外3H-UTP掺入法建立标准脑线粒体体外RNA转录体系(腺苷1mmol/L)。体系分为标准体系腺苷浓度lmmol/L,腺苷2mmol/L,腺苷2mmol/L+腺苷受体拮抗剂CGSl5943,腺苷2mmol/L+腺苷脱氨酶抑制剂Deoxyoformymine。用PCR仪对RNA转录体系产物进行PCR扩增及定性、定量分析。结果:在腺苷浓度2mmol/L的情况下线粒体编码基因-CoxlmRNA的相对表达量与腺苷浓度1mmol/L时的相对表达量相比有明显下降(P<0.05)。在实验腺苷浓度2mmol/L+Deoxyoformymin1umol/L的情况下线粒体编码基因-CoxlmRNA的相对表达量与腺苷浓度2mmol/L再灌注相对表达量两者相比有明显差别,前者高于后者(P>0.05)。在腺苷浓度2mmol/L+CGSl5943lumol/L时再灌CoxlmRNA的相对表达量与腺苷浓度2mmol/L的相对表达量无明显差别(P>0.05)。在实验腺苷浓度2mmol/L的情况下线粒体再灌注编码基因-CoxⅡmRNA的相对表达量与腺苷浓度lmmol/L时的相对表达量相比有降低(P>0.05)。实验腺苷浓度2mmol/L+Deoxyoformyminlumol/L的情况下线粒体编码基因-CoxIImRNA的相对表达量与腺苷浓度2mmol/L的相对表达量两者相比有明显差别,前者高于后者(P>0.05)。在腺苷浓度2mmol/L+CGS159431umol/L时,Cox-ⅡmRNA的相对表达量与实验腺苷浓度2mmol/L的情况下CoxⅡmRNA的相对表达量无明显差别(P>0.05)。线粒体编码基因-CoxⅢmRNA缺血再灌注后腺苷浓度1mmol/L时相对表达量为1.05。腺苷浓度2mmol/L时相对表达量为1.00。腺苷浓度2mmol/L+Deoxyoformymin1umol/L时相对表达量为1.04。腺苷浓度2mmol/L+CGSl59431umol/L时相对表达量为1.03。四者比较无明显差别(P>0.05)。线粒体编码基因-ATPase6mRNA在缺血再灌注腺苷浓度1mmol/L时相对表达量为0.42。腺苷浓度2mmol/L时AT-Pase6mRNA相对表达量为0.56。后者比前者有明显升高(P<0.01)。腺苷浓度2mmol/L+Deoxyoformyminlumol/L时ATPase6mRNA相对表达量与腺苷浓度lmmol/L时相对表达量相比亦有明显升高(P<0.05)。其与腺苷浓度2mmol/L时相对表达量相比也有提高(P<0.05)。腺苷浓度2mmol/L+CGSl59431umol/L时与腺苷浓度2mmol/L时ATPase6mRNA相对表达量无明显差别(P>0.05)。线粒体编码基因-ATPase8mRNA在缺血再灌注腺苷浓度1mmol/L时相对表达量为0.76。腺苷浓度2mmol/L时相对表达量为0.74。腺苷浓度2mmol/L+Deoxyoformymin1umol/L时相对表达量为0.77。腺苷浓度2mmol/L+CGSl59431umol/L时为0.75,四者比较无明显差别(P>0.05)。结论:高浓度ATP对缺血再灌注脑线粒体编码基因的正常表达有负影响,这种影响会加重脑缺血再灌注损伤。ATP影响缺血再灌注脑线粒体编码基因的表达是通过腺苷胞内代谢产物途径而不是通过膜受体途径。     

氯氮平对体外培养大鼠胰岛分泌功能的影响

目的 研究不同浓度氯氮平在不同条件下对外培养大鼠胰岛分泌功能的影响。方法 利用细胞培养技术,在不同葡萄糖浓度(3.3 mmol/L或16.7 mmol/L)和不同作用时间(1 h或4 h)下,以0.2、1、5或10 μmol/L氯氮平作用于大鼠胰岛,用放射免疫分析法测定培养上清液中胰岛素浓度,与相应对照组比较。结果 培养液葡萄糖浓度为3.3 mmol/L,培养1 h,氯氮平各浓度组胰岛素分泌量与对照组相比无显著性差异;培养4 h,4种浓度氯氮平均抑制胰岛素分泌,但各浓度组间无显著性差异。培养液葡萄糖浓度为16.7 mmoL/L,培养1 h或4 h,4种浓度氯氮平均不影响胰岛素分泌。结论 氯氮平抑制基础胰岛素分泌,与剂量无关;胰岛素分泌缺陷和胰岛素抵抗的共同作用可能是氯氮平引起糖代谢异常的机制。     

海藻糖深低温保存外周血造血干细胞的可行性

背景：二甲基亚砜是目前造血干细胞深低温保存的经典保护剂，但其对细胞和患者均有一定的毒副作用。海藻糖是一种稳定的无毒副作用的非还原性双糖，已被广泛应用于红细胞、血小板和胚胎等的冷冻保存中。 目的：探讨海藻糖作为低温保存造血干细胞保护剂的可行性。 方法：外周血造血干细胞经重组人集落刺激因子动员后，用血细胞分离机采集连续单个核细胞，分为0.5 mol/L海藻糖组、1.0 mol/L海藻糖组、对照组。采用程序降温法液氮保存，冻存7 d后取出，立即置于40 ℃水浴箱内复苏。锥虫蓝拒染法检测细胞存活率；采用甲基纤维素半固体培养体系进行集落培养，计数粒-巨噬细胞集落形成单位的回收率；采用CD34-PE/CD45-FITC双标法，流式细胞仪检测CD34+细胞回收率。 结果与结论：与对照组比较，0.5，1.0 mol/L海藻糖组细胞存活率、粒-巨噬细胞集落形成单位回收率、CD34+细胞回收率均明显升高(P < 0.001)，且0.5 mol/L海藻糖组升高幅度尤为显著(P < 0.001或P < 0.01)。证实海藻糖对于短期内低温冻存的外周血造血干细胞有一定保护作用，浓度为0.5 mol/L的海藻糖保护冻存的造血干细胞效果较佳。 关键词：低温保存；粒-巨噬细胞集落形成单位；海藻糖；浓度；外周血造血干细胞；生物材料 doi:10.3969/j.issn.1673-8225.2010.12.008     

体外高浓度葡萄糖培养及黄芪干预人外周血内皮祖细胞的数量和增殖与分化**☆

背景：内皮祖细胞数量及功能受损是糖尿病血管并发症发生发展的重要环节,黄芪对多种原因引起内皮功能障碍具有保护作用,可以有效保护血管内皮功能。 目的：观察高浓度葡萄糖及黄芪干预对人外周血内皮祖细胞数量、增殖及分化影响。 方法：不同浓度葡萄糖孵育内皮祖细胞24 h以及30 mmol/L葡萄糖孵育内皮祖细胞不同时间;内皮祖细胞经20 g/L黄芪预处理24 h后,再加入30 mmol/L葡萄糖培养24 h。 结果与结论：高葡萄糖以浓度及时间依赖方式减少内皮祖细胞的数量,降低内皮祖细胞的增殖及向内皮细胞系分化能力(P < 0.05或0.01),给予黄芪预处理后,内皮祖细胞数量明显增加,增殖及向内皮细胞系分化能力明显增强(P < 0.05或0.01)。提示高葡萄糖以浓度及时间依赖方式减少外周血内皮祖细胞数量,降低内皮祖细胞的增殖及向内皮细胞系分化能力,黄芪可以改善高葡萄糖对内皮祖细胞的损伤作用。     

硬性透气性角膜接触镜材料体外溶菌酶的短期吸附动力学

背景：镜片沉淀物的形成是角膜接触镜配戴的常见问题之一,其中蛋白沉淀最易形成。研究氟硅丙烯酸酯硬镜溶菌酶吸附动力学可进一步完善硬镜蛋白吸附数据,为降低其表面蛋白吸附量和预防硬镜表面污染提供有意义的指导。 目的：考察氟硅丙烯酸酯硬镜在体外对溶菌酶的吸附情况。 方法：配制质量浓度为2.0 g/L溶菌酶溶液(溶液Ⅰ)及不同浓度三氟乙酸溶液;解析率实验,将对照组与实验组镜片浸入溶液Ⅰ37 ℃振荡孵育,Hank’s平衡盐溶液清洗氟硅丙烯酸酯硬镜,然后将对照组镜片浸入去离子水中,实验组镜片浸入不同浓度三氟乙酸,于不同时间点取出;溶菌酶短期吸附动力学实验,对照组镜片浸入去离子水中,实验组镜片浸入溶液Ⅰ37 ℃振荡孵育不同时间点,Hank’s平衡盐溶液清洗氟硅丙烯酸酯硬镜,后用0.2%三氟乙酸解析吸附溶菌酶;BCA法测定各溶液中溶菌酶的量。 结果与结论：氟硅丙烯酸酯硬镜吸附溶菌酶可用三氟乙酸解析,三氟乙酸解析溶菌酶受解析时间和解析浓度的影响。三氟乙酸解析溶菌酶最佳时间1 h,最适浓度0.2%。氟硅丙烯酸酯硬镜吸附溶菌酶(体外模拟24 h),10 min~1 h溶菌酶吸附量递增,1 h达吸附饱和,1~24 h吸附量稳定,饱和吸附量为0.349 mg/cm2。解析时间为10,30 min时,溶菌酶解析率较低,40 min~24 h解析率较好(90%~100%)。 关键词：氟硅丙烯酸酯硬镜;溶菌酶;短期;吸附动力学;解析率 doi:10.3969/j.issn.1673-8225.2010.03.022     

海藻糖对生物人工肝用人永生化肝细胞系C3A细胞低温保存的实验研究

背景：随着生物人工肝在临床上的应用,需要有一种方便、有效、实用的保护生物反应器装载细胞活力及功能的方法,设计有自主知识产权的生物人工肝用肝细胞的低温保护液迫在眉梢。 目的：验证海藻糖作为低温保护剂在4℃低温保存肝细胞的作用。 方法：采用C3A人永生化肝细胞系在不同低温保存液(DMEM培养液;乳酸钠林格氏液,加有不同浓度海藻糖的乳酸钠林格氏液;UW液) 4℃保存24h、48h 及72h。复苏后行细胞活力、细胞损伤指标、氧自由基代谢相关指标等检测,并通过荧光双染法观察细胞凋亡情况。 结果：不同低温保存液保存不同时间的C3A细胞的活力、细胞损伤及细胞凋亡表现均有所不同,其中在同时间点不同浓度海藻糖组均优于单用乳酸钠林格氏液组,但不如UW液组（P<0.01） 。而保存24h的不同浓度海藻糖组及UW液组与乳酸钠林格氏液组相比无显著性差异（P>0.05）,结论：海藻糖能有效减轻低温对肝细胞凋亡及缺血再灌注损伤的程度,因此,可成为低温保存液中有效及重要的保护剂组分。     

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.