世界卫生组织-全球抗癫痫运动中国农村癫痫示范项目结束后四年随访结果

目的了解全球抗癫痫运动中国农村抗癫痫示范项目终止后4年曾接受苯巴比妥治疗的癫痫患者的远期治疗效果及转归,以为我国农村癫痫患者的防治和管理提供参考依据。方法2008年7—12月由经过培训的乡卫生院医师采用问卷与访谈相结合的形式入户调查,对原示范项目6省（市）共8个县经苯巴比妥治疗管理的2455例惊厥型癫痫患者进行随访。结果接受苯巴比妥治疗的2455例患者中共随访到1780例,其中939例（52．75％）继续服药,无发作和发作减少超过50％（有效）的患者于项目终止后的12、24、36和48个月时所占比例分别为66．77％（627／939）、68．37％（642／939）、71．35％（670／939）和73．06％（686／939）;841例（47．25％）停药患者中244例（29．01％）无发作、320例（38．05％）仍然发作但已停药、277例（32．94％）改用其他类型抗癫痫药物。对939例继续服用苯巴比妥与841例停药的癫痫患者进行疗效比较,继续服药者的远期疗效优于停药者（x2=12．423,P=0．002）。停药原因分别为发作停止（244例,29．01％）、改用其他抗癫痫药物（277例,32．94％）、未提供免费药物或无钱买药（93例,11．06％）、治疗效果欠佳（92例,10．94％）、当地买不到苯巴比妥（54例,6．42％）等。至2008年随访结束时共有206例患者死亡,标化死亡比达19．10;其中意外事故死亡为59例（28．64％）,其次为脑血管病30例（14．56％）、癫痫持续状态窒息死亡28例（13．59％）。结论“全球抗癫痫运动”中国农村癫痫示范项目开展成功,远期治疗效果良好,值得进一步推广。癫痫人群死亡率高,尤其是意外事故死亡率高,值得引起注意。     

苯巴比妥口服溶液的制备及质量控制

目的:制备苯巴比妥口服溶液并建立其质量控制方法。方法:以聚乙二醇400、1,2-丙二醇及单糖浆等为辅料制备苯巴比妥口服溶液;采用化学鉴别法和电位滴定法等进行定性鉴别和定量测定。结果:所制备的苯巴比妥口服溶液性状、鉴别、有关物质、含量测定等各项指标均符合2010年版《中国药典》二部附录口服溶液剂的规定。结论:该制剂的制备工艺合理,所建定性、定量方法简便、准确、可靠。     

RP-HPLC法同时测定人血清中4种抗癫痫药的浓度

目的：建立同时测定人血清中拉莫三嗪(LTG)、苯巴比妥(PB)、苯妥英(PHT)和卡马西平(CBZ)浓度的高效液相色谱法。方法血清样品经甲醇沉淀蛋白后直接进样测定。色谱柱采用Waters Symmetry C18柱(250 mm×4.6 mm,5μm),流动相为甲醇-水(55∶45),检测波长235 nm。结果 LTG、PB、PHT和CBZ的线性范围分别是1.56~50、3.13~100、2.19~70、1.09~35μg/ml,平均回收率均>98%。结论本方法操作简便,结果准确,适用于临床治疗药物监测。     

苯巴比妥综合实验的设计与实践

针对药学专业二年级本科生,依托综合性化学实验,从设计思路、教学方案、成效与推广等方面,围绕苯巴比妥设计“合成—精制—结构确证—鉴定分析—含量测定”的综合性实验,以求参与学生达到综合程度高、探究性强、可操作性好等目的。     

高效液相色谱法测定血清中苯巴比妥、苯妥英、卡马西平、氯硝基安定的浓度

目的：建立血清中苯巴比妥（PB）、苯妥英（PT）、卡马西平（CBZ）、氯硝基安定（CNZP）浓度测定的高效液相色谱。方法：以PB、PT互为内标,ODS-Hypersil柱为分析柱,甲醇-水-β-环糊精（45：55：0.01)为流动相;流速为0.8ml/min,紫外检测波长254nm。结果：PB、PT、CBZ、CNZP分离良好,最低检测浓度分别为0.25,0.5,0.05,0.015μg/ml;线性范围分别为2.5-40,2.5-40,1.25-20,0.02-0.32μg/ml;相对回收率分别为97.8%,102.1%,102.3%,103.3%;日蚋、日间RSD均小于10%。结论：该法操作简便,结果可靠,适用于临床开展药物浓度监测。     

肝微粒体酶诱导剂和抑制剂对杀虫单毒性的影响

肝微粒体酶诱导剂苯巴比妥钠能明显延长士的宁急性中毒小鼠的死亡时间(P<0.01),但对杀虫单急性中毒小鼠的死亡时间和死亡数的差异无显著意义(P>0.05)。肝微粒体酶抑制剂氯霉素能增强环己巴比妥的作用,小鼠的入睡时间差别有非常显著意义(P<0.01),死亡数差别有非常显著意义(P<0.001),但对杀虫单急性中毒小鼠的症状出现时间和死亡时间差别均无显著意义(P>0.05)。上述实验结果未能证明肝微粒体酶是杀虫单的主要代谢酶系。     

Cryopreserved precision-cut rat liver slices: morphology and cytochrome P450 isoforms expression after prolonged incubation

Precision-cut liver slices are an accepted in vitro system for toxicological investigations. However, cryopreservation of slices would make a more efficient utilisation, particularly of human liver tissue possible. In the present study sections of cryopreserved male rat liver slices were examined immunohistochemically for cytochrome P450 (CYP) isoforms expression after prolonged incubation and after exposure to typical inducers. Morphologically, with just thawed slices no major alterations were seen, but remarkable cell damage was observed even after 2 h of incubation mainly in the middle of the slices and in the periportal and intermediate regions of the lobules. After 24 h of incubation, viable cells were only observed at the edges of the slices or around bigger vessels. In the viable cells of the cryopreserved liver slices after 2 h of incubation CYP expression pattern was similar to that in normal liver specimens: a low CYP1A1, but a strong CYP2B1 and 3A2 expression predominantly in the central and intermediate lobular zones. After 24 h, the immunostaining for CYP2B1 and 3A2 in the viable cells was reduced, but that for CYP1A1 was increased. Incubation with beta-naphthoflavone further elevated CYP1A1 and 2B1 expression. Phenobarbital caused an enhanced CYP2B1 and 3A2 and dexamethasone and pregnenolone 16 alpha-carbonitrile an increased CYP3A2 immunostaining. These results show that also in cryopreserved liver slices and after a prolonged incubation, a distinct expression pattern and an in vitro induction of phase I enzymes can be demonstrated immunohistochemically.     

WHO“癫痫社会控制”方案在宁夏农村推广性研究

摘要奉文报告了wHO“癫痛社会控制”方寨在宁夏农村进行为期一年的推广性研究结本文报告了WHO“癫痫社会控制”方案在宁夏农村进行为期一年推广性研究结果，并对推广工作中出现的一些问题进行了探讨。在宁夏农村42万人群中调查出癫痫病人711人，按入选条件确定癫痫大发作(强直阵挛性发作)病人502例为治疗观察对象，由经过短期培训的乡村医生负责推广工作，统一使用单一药物苯巴比妥。结果表明苯巴比妥对治疗癫痫大发作病人疗效肯定，乡村医生可以按照规定方案担负起治疗和管理癫痫大发作病人的任务，从而解决广大农村因为缺少神经科医生，众多癫痫病人未能得到合理治疗而产生的社会问题。本研究结果再次证实此方案在我国农村地区是可行的。     

Genetic differences in maternal behaviour patterns in mice administered phenobarbital during pregnancy

In a study designed to examine the role of the genotype on sensitivity to drug-induced behavioural changes, pregnant C57BL/6J and CBA mice were administered 60 mg/kg phenobarbital (PHB) intraperitoneally during days 10–16 of gestation. Following a balanced intrastrain fostering procedure, the behaviour of lactating dams was observed in their home cage at 2, 3, 5, 7 and 14 days postpartum. As the pups became older, maternal behaviour declined in control groups, whereas PHB dams of the CBA strain persisted in nursing their pups. C57 dams were generally affected in an opposite way by PHB exposure. For example, treated dams spent significantly less time in licking behaviour. Nest quality score was especially elevated in PHB dams of the CBA strain, while in C57 dams, nest-building was inhibited and nest quality unaffected by the previous PHB exposure. These results indicate that specific items of maternal behaviour can be differently affected by PHB exposure, and that the responses are affected by the genotype. To summarise, pups raised by treated dams may receive either exaggerated or insufficient maternal attention, as a result of changes in neurotransmitter systems and behavioural regulation following phenobarbital exposure. These results point to the need for a better understanding of mother/pup interactions in studies aimed at characterizing drug and toxicant effects on postnatal development.     

Electrical self-stimulation in the central amygdaloid nucleus after ibotenic acid lesion of the lateral hypothalamus

This experiment was carried out in order to investigate the involvement of lateral hypothalamus (LH) in electrical self-stimulation of the central amygdaloid nucleus (CeA). Adult male Sprague-Dawley rats were bilaterally implanted with a guide cannula situated above each LH and with two electrodes in the CeA. Self-stimulation was subsequently obtained separately from both right and left electrodes. The LH was then lesioned unilaterally by ibotenic acid (IBO) injection. Eight days later, the effect of this unilateral lesion on self-stimulation of the ipsilateral and contralateral CeA was tested. Then the neurons of the remaining non-lesioned LH side were lesioned with IBO and self-stimulation was tested 15 days after the second lesion. Both unilateral as well as bilateral lesions of LH produced a significant decrease in CeA self-stimulation rates but had no significant effect on the reward effectiveness. The unilateral lesions did not produce any modification of the rate-intensity function in the contralateral CeA. This lesion-induced depression in performance was reversed by treatment with phenobarbital. These results provide clear evidence that the rewarding effects of CeA electrical stimulation do not result from the activation of the LH outputs and that the apparent decrease in CeA self-stimulation may result from the LH lesion-induced increase in the frequency of epileptiform manifestations that occur following amygdaloid stimulation.