过氧化物酶体增殖物受体γ共激活因子1与骨骼肌的适应性机制

背景：肌肉收缩活性的增加可诱导多种信号分子转录,并通过专有的信号通路激活细胞核内大量基因的表达。 目的：综述过氧化物酶体增殖物受体γ共激活因子1与骨骼肌的适应机制相关方面的研究。 方法：以PGC1,skeletal muscle,exercise,adaptations为检索词,检索Pubmed数据库(1995/2009-01)。文献检索语种限制为英文。纳入PGC1与运动性骨骼肌适应的相关内容。排除重复性研究。以PGC1与线粒体的氧化代谢,以及运动诱导PGC1s变化与骨骼肌适应为评价指标。 结果与结论：计算机初检得到57篇文献,根据纳入排除标准,对34篇进行分析。长期的耐力训练可诱导骨骼肌发生可塑性变化,包括线粒体的生物合成、肌纤维类型的改变和毛细血管密度的增加。转录因子高度依赖共激活分子从转录水平调控这些运动诱导生理性适应过程。这些转录因子的目标基因大部分涉及到线粒体的生物合成和细胞的新陈代谢,其转录调控方式可能为了解运动性能量变化特征的信号通路与线粒体生物合成及其功能之间的关系提供基本框架。提示过氧化物酶体增殖物受体γ共激活因子1α蛋白自身转录后,存在多种蛋白修饰,与多种生物学过程密切相关,可能在运动诱导骨骼肌的适应机制方面起着重要作用。     

骨骼肌兴奋收缩偶联与细胞内的钙稳态★

背景：在骨骼肌胞浆内，Ca2+是神经兴奋和肌肉收缩之间的重要偶联因子，控制着肌肉收缩的启动和舒张的终止，对骨骼肌的兴奋收缩偶联起着不可或缺的作用，骨骼肌的兴奋收缩偶联与细胞内钙稳态的变化紧密相关。 目的：研究近年来骨骼肌细胞内钙调控机制的研究进展及钙稳态与运动之关系的进展。 方法：电子检索CNKI数据库、读秀学术搜索等中文数据库和Elsevier SD，Springer Link等英文数据库1980/2010收录的骨骼肌兴奋收缩偶联和钙稳态的相关综述和实验研究报告，分析骨骼肌细胞内钙调控机制的研究进展及钙稳态与运动之关系的研究进展。 结果与结论：共纳入骨骼肌兴奋收缩偶联与钙稳态相关文献43篇。骨骼肌的兴奋收缩偶联与细胞内钙稳态之间有着密不可分的关系，但骨骼肌内钙稳态的调控机制还不甚明朗，尚期待大量研究。对运动与肌细胞内钙稳态的关系的研究也仍需要进一步努力，探索适宜适当的运动，探索运动性疲劳的发病机制，有效预防和对抗运动性疲劳及肌肉损伤仍将是研究者的工作重点。     

卫星细胞与肌肉肥大关系及成肌因子的运动性调控

背景：卫星细胞是成体肌肉发生重要的“原料”，它的增殖、分化和融合增加了肌纤维的细胞核数量或肌纤维数的数量，继而引起肌肉功能和形态学的变化，但是肌肉肥大是否一定有卫星细胞参与还存在争议。成肌因子是肌肉发生调节的核心因子，在肌肉发生的多个阶段发挥重要作用，但是目前对它们功能上特点和差异的了解仍然不够深入。 目的：总结并讨论卫星细胞和成肌因子在肌肉发生和肌肉肥大以及在肌肉训练中的作用。 方法：由第一作者用计算机检索中国期刊全文数据库(CNKI：2000/2010)和Medline(2000/2010)数据库，检索词分别为“骨骼肌，肥大，运动，肌肉发生，卫星细胞，成肌因子”和“skeletal muscle，hypertrophy，exercise，myogenesis，satellite cell，MRF”，语言分别设定为中文和英文。从卫星细胞与肌肉肥大、成肌因子的作用及成肌因子的运动性调控特点2方面进行总结，对卫星细胞及成肌因子在肌肉发生中的作用及其调节机制和肌肉重塑等方面进行介绍。 结果与结论：共检索到177篇文章，按纳入和排除标准对文献进行筛选，共纳入30篇文章。结果表明肌肉发生是肌肉肥大的生物学基础，卫星细胞是成体肌肉发生关键，但肌肉肥大早期过程可能没有卫星细胞的参与，以DNA含量来衡量卫星细胞改变可能有较大误差，成肌因子是肌肉发生核心因子。目前研究对成肌因子成员之间功能的异同和成肌因子的运动性调控特点的了解仍不深入。     

骨骼肌细胞线粒体通透性转换孔及bcl-2和bax mRNA表达与运动

背景：运动影响骨骼肌细胞的凋亡,而线粒体途径是介导细胞凋亡的一个重要途径。 目的：研究运动对大鼠骨骼肌线粒体通透性转换孔、凋亡调控基因bcl-2和bax表达的影响。 方法：将24只成年雄性SD大鼠随机分为3组：对照组正常饲养,6周游泳训练组进行6周的游泳训练,每周6次,一次性游泳力竭组于第6周进行一次力竭性游泳运动。应用紫外分光光度仪检测各组大鼠骨骼肌线粒体通透性转换孔的开放情况,应用RT-PCR测定大鼠骨骼肌bcl-2和bax mRNA的表达。 结果与结论：与对照组比较,6周游泳训练组大鼠骨骼肌线粒体通透性转换孔的开放程度变化不明显,bcl-2 mRNA的表达显著增加,bax mRNA的表达显著减少,bcl-2/bax mRNA比值显著增大(P < 0.01)。与对照组比较,一次性游泳力竭组大鼠骨骼肌线粒体通透性转换孔开放程度明显增加(P < 0.01),bcl-2 mRNA的表达显著减少,bax mRNA的表达显著增加,bcl-2/bax mRNA比值显著减小(P < 0.01)。说明运动训练可通过改变线粒体通透性转换孔的开放、调节bcl-2/bax表达,调控骨骼肌细胞凋亡。     

干细胞与运动性骨骼肌细胞凋亡

背景：运动性骨骼肌细胞凋亡业已成为当前运动医学领域的研究重点,干细胞应用于运动性伤病的恢复和防治也有报道,但将干细胞用于细胞凋亡干预作用的相关研究还很少。 目的：总结干细胞防治运动性骨骼肌细胞凋亡的作用及其机制,为科学的运动训练和体育锻炼提供依据。 方法：通过计算机检索PubMed数据库1991-01/2009-10的相关文献,检索词为“Exercise Training,Sports,Skeletal Muscle,Apoptosis”,并限定文章语言种类为English。同时计算机检索中国期刊全文数据库1994-01/2009-10的相关文献,检索词“干细胞、运动、骨骼肌、细胞凋亡”,并限定文章语言种类为中文。纳入标准：①文章所述内容应与干细胞及其骨骼肌细胞凋亡的研究密切相关。②同一领域选择近期发表或在权威杂志上发表的文章。排除标准：①重复性研究。②Meta分析。 结果与结论：共检索到360篇文献,对资料进行初审,文献的来源主要是通过对干细胞及其在运动医学领域的研究进展,以及骨骼肌细胞凋亡的变化与发展趋势等的应用情况进行汇总分析,共选取31篇文献,其中21篇为综述,其余均为临床或基础实验研究。大强度的运动可引起骨骼肌细胞出现凋亡,而运用干细胞技术可在一定程度上起到预防细胞凋亡的作用,干细胞可通过调节Bcl-2和Bax蛋白表达来防治运动过程中出现的骨骼肌细胞凋亡,从而促进运动机体骨骼肌的早期恢复。     

光生物调节修复运动性肌肉损伤

背景：不习惯强度的运动常导致运动性肌肉损伤,光生物调节治疗运动性肌肉损伤的研究存在不同的结果,且其治疗机制及其量效关系尚不清楚。 目的：总结和分析光生物调节作用的机制以及光生物调节疗法治疗运动性肌肉损伤时的剂量、强度、波长等与效应之间的关系。 方法：通过PubMed数据库(1996-01/2010-04)和中国学术期刊库(2000-01/2010-04)检索了低强度激光或单色光对运动性肌肉损伤的作用及其相关机制的文献,英文检索词为“low-level laser, phototherapy, exercise-induced muscle damage, delayed onset muscle soreness”,中文检索词为“低强度激光,光疗法,运动性肌肉损伤,延迟性肌肉酸痛”。手工补充检索低强度激光疗法的专著。共收集到中、英文文献38篇,排除重复及类似性研究,纳入31篇文献进行综述。 结果与结论：光生物调节作用的机制假说主要包括线粒体机制、一氧化氮机制、氧化还原机制和光生物信息模型理论,光生物调节疗法治疗运动性肌肉损伤的具体机制仍不清楚。光生物调节治疗运动性肌肉损伤只有在剂量和强度达到足够大情况下才有效,而且强度可能比剂量更重要,患部的有效照射剂量和强度受到皮肤厚度和光波波长的影响。由此推论,光生物调节疗法能有效地治疗运动性肌肉损伤,其疗效是剂量和强度依赖性的。     

运动对骨骼肌丝裂原活化蛋白激酶信号系统的影响

背景：丝裂原活化蛋白激酶是生物体内重要的信号转导系统之一，参与介导生长、发育、分裂、分化、死亡以及细胞间的功能同步等多种细胞过程。 目的：总结丝裂原活化蛋白激酶对运动后骨骼肌适应性变化的重要作用。 方法：采用计算机检索中国期刊全文数据及PubMed数据库1990-01/2009-06期间的相关文章，检索词为“运动；丝裂原活化蛋白激酶信号系统；骨骼肌；适应，Exercise；Mitogen-activated protein kinases；skeletal muscle；adaption”。纳入与运动和丝裂原活化蛋白激酶信号系统研究现状与发展密切相关的文章，排除重复性研究。 结果与结论：运动能够激活骨骼肌中丝裂原活化蛋白激酶信号传导系统，不同运动方式、不同类型的肌肉以及训练的时间长短都可以影响到丝裂原活化蛋白激酶的激活，而且激活后丝裂原活化蛋白激酶具有不同的时相性，丝裂原活化蛋白激酶对运动后骨骼肌的适应性变化具有重要作用。通过研究探索丝裂原活化蛋白激酶对运动后骨骼肌的适应性变化，有利于以运动相关的丝裂原活化蛋白激酶为靶点，研制和开发运动功能性食品或抗疲劳药物。     

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。     

骨骼肌的运动适应机制

背景：骨骼肌运动适应机制的研究对提高运动成绩,预防和治疗一些代谢紊乱性疾病具有重要意义。 目的：探讨骨骼肌运动适应的机制。 方法：应用计算机检索PubMed数据库和中文期刊全文数据库2011-03前发表的相关文章,检索词分别为“skeletal muscle, exercise, adaptation, cytoskeleton, dystrophin”和“骨骼肌,运动,适应,骨架蛋白,肌营养不良蛋白”,共检索到56篇文献,纳入所述内容与骨骼肌运动适应机制相关的文献,排除重复性研究,保留31篇进行综述。 结果与结论：激烈的运动使肌肉结构和细胞代谢产生应激反应,包括肌肉损伤和氧化应激反应。高强度的离心运动可造成肌肉超微结构损伤,但运动性肌损伤后存在肌肉再重建反应。运动训练可促进健康的个体对一氧化氮系统产生各种各样的适应,通过各种机制增强骨骼肌的生物学有效性,这些适应性变化可有效增加运动能力,对心血管系统具有保护作用。目前,大多数人类骨骼肌运动适应机制还没有被发现。     

肌肉萎缩与过氧化体增殖活化受体γ辅助活化因子1α的关系

背景：过氧化体增殖活化受体γ辅助活化因子1α(peroxisome proliferator-activated receptor γ coactivator 1α,PGC-1α)能调节骨骼肌的功能,包括有：线粒体的生物发生、底物氧化和肌纤维类型等,最近还有研究发现PGC-1α能够预防肌肉的萎缩。 目的：总结并讨论PGC-1α与肌肉萎缩之间的关系。 方法：由第一作者用计算机检索中国期刊全文数据库(CNKI：2000/2010)和Medline数据库(2000/2010),关键词分别为“肌肉萎缩,PGC-1α,运动”和“muscle atrophy,PGC-1α,exercise”。共检索到56篇文章,按纳入和排除标准对文献进行筛选,共纳入22篇文章。从PGC-1α与肌肉萎缩、运动与PGC-1α共2个方面进行总结。 结果与结论：PGC-1α表达增强能提高线粒体功能、人体的运动能力、降低氧化应激和抑制肌肉萎缩特异性基因的表达。说明运动可通过调节PGC-1α的表达来干预肌肉萎缩。     

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.