维生素E对离心运动后大鼠骨骼肌线粒体内丙二醛、超氧化物歧化酶的影响

背景：许多实验表明自由基的增加与骨骼肌运动性损伤有关，而维生素E作为一种抗氧化剂，具有清除自由基的功效，可减轻运动中抗氧化酶所受的自由基损伤，减缓疲劳出现，进而提高运动能力。 目的：从细胞线粒体自由基代谢的角度，探讨维生素E对离心运动后大鼠骨骼肌细胞线粒体丙二醛、超氧化物歧化酶的影响，以进一步阐明维生素E抗骨骼肌运动性损伤的内在机制。 设计、时间及地点：随机分组，动物实验观察，于2007-05/10在沈阳体育学院国家体育总局重点实验室和中国医科大学重点实验室完成。 材料：雄性SD大鼠48只，体质量(304±12) g。随机分为对照组、运动组、生理盐水组、维生素E组，12只/组。 方法：维生素E组腹腔注射维生素 E胶丸，1.0~1.2 mg/kg，总量为4 mL/kg，初次注射时间为鼠正式实验前1 d，以后每8 h注射1次，共4次。生理盐水组以生理盐水为对照，注射方式、注射量及运动方式、处死时间同维生素E组。运动组只进行运动，不给予药物或生理盐水，对照组仅为常规饲养，无任何干预。采用一次力竭性下坡跑运动建造大鼠损伤模型，运动结束后，取大鼠右侧肱三头肌。 主要观察指标：采用微量测定试剂盒和6010紫外-可见分光光度计测定丙二醛含量及超氧化物歧化酶活力。 结果：肱三头肌细胞线粒体各组丙二醛、超氧化物歧化酶在离心运动后24 h均显著增加(P < 0.01)。与运动组比较，生理盐水组丙二醛、超氧化物歧化酶值均无显著性差异(P > 0.05)，维生素E组丙二醛显著降低(P < 0.01)，而超氧化物歧化酶显著增高(P < 0.01)。 结论：补充维生素E可降低骨骼肌细胞线粒体丙二醛的含量，增加细胞线粒体超氧化物歧化酶的活性，提高骨骼肌细胞的抗氧化能力，进而可减轻自由基对肌肉的损伤作用。维生素E对运动性骨骼肌损伤的预防作用主要是通过维生素E的抗氧化作用完成的。     

耐力训练模型大鼠骨骼肌代谢酶与自由基变化

背景：骨骼肌代谢酶与自由基的变化与不同的运动方式和运动强度有关。 目的：观察递增大强度耐力训练下大鼠骨骼肌代谢酶活性和自由基代谢的变化。 方法：健康雄性SD大鼠,随机分为安静组和运动组,后者建立8周的递增大强度耐力训练模型,训练结束后取骨骼肌样本测试肌酸激酶、乳酸脱氢酶、谷草转氨酶、谷丙转氨酶、丙二醛、总抗氧化酶、过氧化氢酶水平。 结果与结论：8周训练后,运动组大鼠肌酸激酶、乳酸脱氢酶、谷草转氨酶、谷丙转氨酶酶活性及丙二醛水平均高于安静组(P < 0.01或0.05),而总抗氧化酶、过氧化氢酶、谷胱甘肽过氧化物酶活性低于安静组(P < 0.05)。说明8周的递增大强度的耐力训练能使骨骼肌受到一定的损伤,并且提示抗氧化酶活性的下降和部分代谢酶活性以升高之间有一定的关系。     

维生素E对离心运动大鼠骨骼肌超微结构的影响

背景：维生素E作为一种抗氧化剂,具有清除自由基的功效,可减轻运动中抗氧化酶所受的自由基损伤,减缓疲劳出现,从而提高运动能力。 目的：通过维生素E对骨骼肌运动性损伤的干预,探讨其对骨骼肌运动性损伤形态学变化的影响,为骨骼肌运动性损伤的形态学研究和抗损伤机制的探索提供实验依据。 设计、时间及地点：随机分组,动物实验,于2007-05/10在沈阳体育学院国家体育总局重点实验室和中国医科大学电镜中心完成。 材料：雄性SD大鼠16只,随机均分为对照组、运动组、生理盐水组、维生素E组。 方法：维生素E组于实验前1 d腹腔注射维生素E胶丸,注射量为1.0~1.2 mg/kg,总量为4 mL/kg,每8 h注射1次,共4次。生理盐水组以生理盐水为对照,注射方式、注射量及处死时间同维生素E组。运动组只进行运动,不给予药物或生理盐水,对照组仅为常规饲养,无任何干预。采用一次力竭性下坡跑运动建造大鼠损伤模型,运动结束后,取大鼠右侧肱三头肌,制做电镜标本。 主要观察指标：肌原纤维和肌节排列情况;Z线异常变化;细胞膜、细胞核、线粒体、肌浆网、T小管、卫星细胞等形态学改变。 结果：补充维生素E组后,骨骼肌损伤的超微结构改变有明显的改善,虽然肌浆网尚有水肿表现,但肌纤维排列基本整齐,Z线明暗带清晰,细胞核清楚。 结论：补充维生素E可有效地减少离心运动对骨骼肌肌纤维损伤的形态学改变,肌纤维排列更加整齐、肌节更加清晰,其作用可能与维生素E的抗氧化和促进蛋白质的合成功能等因素有关。     

针刺及艾灸足三里穴缓解大鼠运动疲劳作用的比较

背景：已有诸多实验证实针灸足三里穴能够有效地缓解运动疲劳。 目的：观察毫针针刺及艾灸足三里穴(ST36)对运动疲劳大鼠的运动耐力、骨骼肌微循环及抗氧化酶活性的影响,探讨针刺及艾灸两种不同疗法缓解运动疲劳作用的差异。 设计、时间及地点：随机动物实验,于2008-06/07在华南师范大学光子中医学实验室完成。 材料：SPF级雄性成年SD大鼠24只,体质量220~260 g。 方法：SD大鼠24只,适应性游泳后被随机分为正常对照组、模型组、艾灸组及针刺组,每组6只。采用无负重游泳方式建立大鼠运动疲劳模型,艾灸组及针刺组在游泳运动的同时,分别采用毫针及艾灸刺激足三里穴,1次/d,共10 d。末次力竭运动结束后检测指标。 主要观察指标：大鼠骨骼肌微循环及线粒体内超氧化物歧化酶、谷胱甘肽过氧化酶的活性。 结果：实验第9天,艾灸组大鼠的运动耐力显著高于同时间点模型组的运动耐力(P < 0.05);实验第11天,艾灸组和针刺组的大鼠的运动耐力均显著高于模型组的大鼠同时间点的运动耐力(P < 0.05),艾灸组和针刺组相比差异无显著性意义 (P > 0.05)。艾灸组双侧胫骨前肌的血流灌注量均显著高于模型组(P < 0.05);针刺组腹直肌的血流灌注量显著高于模型组(P < 0.05)。艾灸组双侧胫骨前肌线粒体内的超氧化物歧化酶、谷胱甘肽过氧化物酶活性显著高于模型组(P < 0.05); 针刺组双侧胫骨前肌线粒体内的超氧化物歧化酶、谷胱甘肽过氧化物酶活性显著低于艾灸组(P < 0.05)。 结论：艾灸足三里穴能够有效地提高运动疲劳大鼠骨骼肌线粒体抗氧化酶活性、增加骨骼肌血流灌注,缓解外周骨骼肌的运动疲劳,提高运动耐力,其效应优于针刺足三里穴。     

牛磺酸降低局灶性脑缺血引起的能量代谢紊乱和氧化损伤

目的观察牛磺酸对大鼠局灶性脑缺血引起的能量代谢紊乱和氧化损伤的影响。方法建立大鼠动脉腔内插线局灶性脑缺血模型,在缺血1h后给予牛磺酸(50mg/kg,iv),测定缺血2h再灌注22h时脑组织内ATP、乳酸和丙二醛(MDA)的含量、髓过氧化物酶(MPO)和超氧化物歧化酶(SOD)的活性及总抗氧化能力。结果牛磺酸明显降低再灌注22h时缺血脑组织内乳酸和MDA的含量及MPO活性,升高ATP的含量、SOD的活性和总抗氧化能力。结论牛磺酸可改善局灶性脑缺血损伤后的能量代谢,降低中性粒细胞的浸润,提高缺血组织的抗氧化能力,减轻局灶性脑缺血引起的过氧化损伤。     

热应激预处理对离心运动大鼠骨骼肌自由基代谢的影响

背景：研究表明热预处理能够提高肌肉抗损伤的能力，但具体的机制尚不清楚。 目的：观察热应激预处理对离心运动大鼠骨骼肌超氧化物歧化酶活性及丙二醛含量的影响。 方法：雄性Wistar大鼠随机分为对照组、离心运动组、预热应激+离心运动组。热应激温度为43 ℃，时间约35 min。采用-16°下坡跑台跑做大负荷间歇性离心运动，跑速为26.8 m/min，运动5 min，间歇1 min，共进行10组。分别于运动前1 h、运动后1，24，48 h取大鼠腓肠肌，采用硫代巴比妥酸法测定大鼠丙二醛含量，黄嘌呤氧化酶法测定超氧化物歧化酶活性。 结果与结论：与对照组比较，离心运动组大鼠腓肠肌丙二醛含量显著增高(P < 0.05)，并随运动后时间的延长逐渐升高，超氧化物歧化酶活性随运动后时间的延长显著降低(P < 0.05)。与离心运动组比较，预热应激+离心运动组大鼠腓肠肌超氧化物歧化酶活性显著增高(P < 0.05)，丙二醛含量显著降低(P < 0.05)。说明热应激预处理可增强骨骼肌超氧化物歧化酶活性，降低丙二醛含量，对离心运动损伤有保护作用。     

玉米黄质对高脂诱发鹌鹑模型血管脂质过氧化损伤的保护作用*

背景：大多数人工合成的抗氧化药物长期应用均有一定的毒副作用,玉米黄质作为天然药物有其独特的生理效应。 目的：观察玉米黄质对高脂诱发血管脂质过氧化损伤效应鹌鹑模型影响的量效关系。 方法：建立鹌鹑高脂模型,利用玉米黄质按30,60mg/kg灌胃7周后,取空腹血测定血清总胆固醇、三酰甘油、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇及丙二醛水平、血清超氧化物歧化酶、谷胱甘肽过氧化物酶及诱导型一氧化氮合酶活性;检测各组动物肝脏组织中总胆固醇、三酰甘油水平;并采用苏木精-伊红染色观察主动脉血管病理变化。 结果与结论：与高脂模型组相比,玉米黄质组血清三酰甘油、总胆固醇和低密度脂蛋白胆固醇浓度明显降低,而血清高密度脂蛋白胆固醇浓度明显增高;肝脏总三酰甘油及总胆固醇的合成也受到强烈抑制;玉米黄质组血清超氧化物歧化酶活性、谷胱甘肽过氧化物酶活性明显提高,而诱导型一氧化氮合酶活性下降、丙二醛水平减少。说明玉米黄质具有良好的降脂功效,对高脂诱导的血管脂质过氧化损伤有明显的抑制作用,且高剂量较低剂量作用效果更为理想。     

雌激素替代抑制萘诱导去卵巢大鼠的晶状体氧化损伤*

背景：抗氧化作用可能是雌激素对晶状体保护作用的机制之一,但此机制的具体途径目前仍不明确,同时临床上常用的几种雌激素替代治疗方法对晶状体氧化损伤的影响至今少见报道。 目的：观察雌二醇及其联合孕酮对萘诱导去卵巢雌性大鼠晶状体氧化损伤模型中晶状体混浊情况、晶状体氧化防御系统、脂质过氧化产物及可溶性蛋白水平的影响。 方法：将SD大鼠随机分为假手术组、模型组、雌二醇组、雌二醇+孕酮组,后3组均行双侧卵巢切除。术后2周,4组均用萘混悬液灌胃,定期行裂隙灯显微镜检查观察各组大鼠晶状体变化;灌胃6周后检测晶状体氧化防御系统、脂质过氧化产物及可溶性蛋白水平,测定血清雌二醇和孕酮水平。 结果与结论：与模型组相比,雌二醇组、雌二醇+孕酮组及假手术组晶状体混浊程度轻,出现时间晚,而晶状体超氧化物歧化酶、谷胱甘肽、维生素C,可溶性蛋白含量,血清雌二醇与孕酮水平增高(P < 0.05或P < 0.01),丙二醛水平降低(P < 0.05)。结果证实,雌二醇及其联合孕酮两种替代治疗方法对萘诱导去卵巢雌性大鼠晶状体的氧化损伤均有抑制作用,其机制与晶状体氧化防御系统的活性、抑制脂质过氧化产物的形成并维持可溶性蛋白的水平有关,抑制晶状体的氧化损伤是雌激素替代治疗发挥晶状体保护作用的机制之一。     

无氧间歇训练对大鼠骨骼肌、心肌、肝脏自由基代谢的影响

背景：无氧间歇训练法是一种被广泛应用的重要训练方法，有关此训练对机体自由基代谢及其抗氧化酶活性影响的系统性研究较少。 目的：观察无氧间歇训练对大鼠体内自由基代谢的影响。 设计、时间及地点：随机对照动物实验，于2008-03/05在徐州师范大学运动生理实验室完成。 材料：健康雄性SD大鼠32只，体质量230~270 g，随机分为安静对照组，间歇训练对照组，间歇运动即刻组，间歇训练即刻组，每组8只。 方法：安静对照组不进行训练，间歇训练对照组和间歇训练即刻组进行跑步运动，以坡度10°，速度26.8 m/min运动1 min，后以坡度为0，速度5 m/min休息3 min，每天连续20次不间断，5 d/周，运动6周。间歇运动即刻组只在第6周最后一天进行一次运动。 主要观察指标：6周运动结束后即刻麻醉下处死各组大鼠，测定其骨骼肌，心肌，肝脏超氧化物歧化化酶，谷胱甘肽过氧化物酶，过氧化氢酶，丙二醛。 结果：①训练组运动后即刻各组织超氧化物歧化酶活性均显著高于间歇运动即刻组(P < 0.05)。②间歇运动即刻组股四头肌、心肌谷胱甘肽过氧化物酶活性显著低于安静对照组(P < 0.05)，丙二醛含量显著高于安静对照组(P < 0.05)，股四头肌和肝脏过氧化氢酶活性显著高于安静对照组(P < 0.05)。③间歇训练即刻组股四头肌、心肌谷胱甘肽过氧化物酶活性显著高于间歇运动即刻组(P < 0.05)，丙二醛含量明显低于间歇运动即刻组(P < 0.05)，股四头肌和心肌过氧化氢酶活性显著高于间歇运动即刻组(P < 0.05)。 结论：无氧间歇训练可以使机体抗氧化酶活性发生适应性变化，自由基清除能力增强。     

白藜芦醇对离心运动后骨骼肌微损伤的修复

背景：白藜芦醇是一种天然的抗氧化剂和自由基廓清剂,具有清除自由基、减轻脂质过氧化等重要药理作用,目前有关白藜芦醇在减轻骨骼肌损伤、促进损伤修复方面的研究尚不多见。 目的：观察白藜芦醇对离心运动后骨骼肌超微结构损伤、血清丙二醛和肌细胞浆Ca2+浓度的影响。 设计、时间及地点：对照观察动物实验,于2007-08/2008-06在南方医科大学完成。 材料：成年雄性SD大鼠72只,实验室适应性喂养3 d后随机分为蒸馏水组(n=40)、白藜芦醇组(n=32)。白藜芦醇制剂购自湖南省洪江华光生物有限公司。 方法：白藜芦醇组大鼠每日腹腔注射1次白藜芦醇制剂60 mg/kg,蒸馏水组大鼠腹腔注射等量蒸馏水,连续2周。2周后,将大鼠在动物跑台上进行一次性下坡跑运动,速度为16 m/min,下坡坡度为16°,5 min运动,2 min休息,总运动时间为120 min。运动过程中采用人工驱赶和声刺激,不使用电刺激。 主要观察指标：于运动前、运动后即刻、运动后24,48,72 h电镜下观察比目鱼肌纤维Z线,TAB法测定血清丙二醛和流式细胞仪检测肌细胞浆Ca2+浓度。 结果：与蒸馏水组比较,白藜芦醇组镜下肌纤维损伤程度减轻,骨骼肌细胞Z线异常百分率在运动后即刻、运动后24,48,72 h比蒸馏水组分别降低了50.34%,52.67%,52.65%和53.26%(P < 0.05),离心运动引起的血清丙二醛升高程度分别下降了27.7%,29.56%,34.38%和27.79%(P < 0.05),胞浆Ca2+浓度分别降低了27.53%,25.84%,22.14%和11.62% (P < 0.05)。 结论：白藜芦醇可降低离心运动后血清丙二醛浓度和肌细胞浆Ca2+浓度,减轻运动导致的肌肉损伤。     

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.     

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.     

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.     

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.     

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.     

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.