骨骼肌细胞与热休克蛋白★

背景：骨骼肌含有多种热休克蛋白，可能具有重要的生理功能。 目的：综述骨骼肌热休克蛋白的特性，以及骨骼肌热休克蛋白在生理及病理情况下表达的意义。 方法：以“热休克蛋白，骨骼肌，运动，缺血再灌注”为中文检索词，以“heat shock proteins, skeletal muscle, exercise, ischemia-reperfusion”为英文检索词，应用计算机检索Pubmed数据库和中文期刊全文数据库2010-06前发表的相关文章。纳入与骨骼肌细胞热休克蛋白研究相关的文献，排除重复性研究。 结果与结论：共检索到197篇文献，排除无关重复的文献，保留35篇文献进行综述。目前研究证实骨骼肌含有多种热休克蛋白，主要有小热休克蛋白，热休克蛋白70，热休克蛋白60和热休克蛋白90等。热休克蛋白作为应激的指标，可以反映运动时细胞内发生的变化，对监控过度训练有重要意义。同时热休克蛋白在过度训练或肌肉损伤时对保持肌肉功能起重要作用。     

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。     

骨骼肌钙释放通道与运动☆

学术背景：骨骼肌Ca2+释放通道是骨骼肌内质网Ca2+释放与摄取的主要结构，与骨骼肌兴奋－收缩耦联密切相关，直接影响着骨骼肌的运动功能，尤其是骨骼肌的收缩速度与力量。目前，研究运动时骨骼骨钙释放通道的结构与功能的变化对于正确认识运动对骨骼肌的生物学作用，提高骨骼肌的收缩速度与力量具有重要的意义，也是某些相关疾病的运动康复与治疗的研究热点之一。 目的：总结骨骼肌钙释放通道的特性及其运动时功能变化的研究进展。 检索策略：由该论文的研究人员检索PubMed数据库2000-01/2007-06的相关文献，检索词“RYR1，exercise”，限定文章语言种类为English。同时检索中国期刊全文数据库、万方数据库2000-01/2007-04 期间的相关文章，检索词“骨骼肌钙释放通道；运动”，限定文章语言种类为中文。共检索到42篇文献，对资料进行初审，纳入标准：①与骨骼肌钙释放通道运动时结构与功能的变化密切相关。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：重复性研究。 文献评价：文献的来源主要是骨骼肌Ca2+释放通道在不同运动方式方面的随机对照试验。所选用的30篇文献中，6篇为综述，24篇为临床或基础实验研究。 资料综合：①骨骼肌钙释放通道是调节骨骼肌细胞内Ca2+浓度的重要蛋白之一，直接参与了骨骼肌的兴奋收缩耦联过程。②有许多调节因素，如一些内源性蛋白（FK结合蛋白、钙调素、钙结合蛋白）和一些离子（Ca2+、Mg2+），通过不同的作用位点与骨骼肌钙释放通道结合，调控骨骼肌钙释放通道的结构与功能。③研究表明，骨骼肌在运动训练后通过二氢吡啶受体和骨骼肌钙释放通道这二种受体蛋白的表达水平提高而增强了肌肉的速度与力量能力；不同运动方式对骨骼肌钙释放通道的影响具有不同的特点。④关于骨骼肌钙释放通道方面的研究虽已取得较大进展，但仍存在许多问题，如骨骼肌兴奋收缩耦联调控机制不十分清楚；不同运动方式对骨骼肌钙释放通道的影响规律有待进一步研究；关于运动影响骨骼肌肌浆网上钙释放通道对Ca2+的转运能力的研究主要是急性运动，对于速度力量性运动方式和长期运动训练对其影响的规律还未见系统报道。 结论：骨骼肌钙释放通道上Ca2+的释放与摄取是影响骨骼肌收缩功能的重要基础，不同运动对骨骼肌钙释放通道的影响有不同的规律。     

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。     

骨骼肌生长与适应的机械信号与途径

背景：骨骼肌作为一种机械组织,具有机械收缩的功能,但外界力学机械信号如何转变成生物体的化学信号,从而影响肌肉的生长和代谢仍不是很明确。 目的：了解机械刺激与骨骼肌适应的信号途径,为摸索改善骨骼肌质量与适应提供理论依据及实验方案。 方法：应用计算机检索Pubmed数据库和中国期刊网1980-01/2008-12相关文献。英文检索词为“skeletal muscle、mechanical stimulation、signal transduction”;中文检索词为“骨骼肌,运动,信号传导”。纳入标准：①具有原创性,论点论据可靠的实验性文章。②与骨骼肌肥大相关内容的文章。③观点明确,分析全面的文章。排除标准：与文章目的无关的内容和重复性研究。 结果与结论：骨骼肌作为一种机械组织,具有机械收缩的功能,但外界力学机械信号如何转变成生物体的的化学信号,从而影响肌肉的生长和代谢仍不是很明确。研究表明,机械刺激通过诱导Akt/mTOR途径,从而促进骨骼肌生长与适应的机制;骨骼肌纤维在机械运动刺激作用下,神经冲动的传递,随后开放Ca2+及相关离子通道,引起胞浆中的钙离子增加,使钙调神经磷酸酶的活性上升,催化NFAT 去磷酸化,激活的NFAT 进入肌细胞核,作用于相应的靶基因,最终使骨骼肌产生运动适应性变化。结果表明,肌肉机械信号刺激促进胰岛素样生长因子1的释放,进而通过生物信号传导通路来实现。机械刺激促进离子浓度的改变,从而影响钙调磷酸酶/对核因子活化T细胞途径以增加肌肉质量。对于机械运动的物理信号与生物体的化学信号通路的机制研究还有待继续深入探索。     

骨骼肌细胞中热休克蛋白72表达与运动及肌肉损伤

背景：运动应激诱导的骨骼肌细胞中热休克蛋白72的表达与肌肉损伤程度大小有关。 目的：综述骨骼肌细胞中热休克蛋白72在运动中的表达及其与运动的相互关系,并对其在运动医学领域中潜在的研究价值进行了探讨。 方法：应用计算机检索国家科技文献图书中心1990-01/2009-10的相关文献,检索词“heat shock protein 72, skeletal muscle”,限定文章语言种类为“English”;同时计算机检索万方数据库1994-01/2009-10的相关文献,检索词“热休克蛋白72,骨骼肌”,限定文章语言种类为中文。并通过手工检索相关文献。纳入具有原创性,论点论据可靠,观点明确,分析全面,文献主题内容与此论文联系密切的文章。排除实验设计不合理的文章及观点模糊的综述。 结果与结论：热休克蛋白广泛存在于生物界,对机体具有保护作用。运动应激诱导骨骼肌细胞中热休克蛋白72mRNA 的表达及热休克蛋白72的合成与运动负荷量、运动强度和持续时间密切相关,尤其是运动强度。热休克蛋白72在骨骼肌细胞受到过强应激时,其合成量非但没有减弱相反明显增加。作为肌肉应激指标,热休克蛋白72提供了运动引起的骨骼肌细胞功能变化的重要信息,对预防过度训练和确定随后的训练计划可能是一个很好的量化指标。     

机械生长因子对骨骼肌卫星细胞的调控

背景：机械生长因子作为胰岛素样生长因子1的一个亚型,有促进肌卫星细胞增殖,抑制分化的功能,因此利用外源性机械生长因子类物质对卫星细胞进行干预,并对其调控的分子机制进行研究,可以为骨骼肌疾病的临床治疗及组织工程学的研究提供新的思路。 目的：综合分析机械生长因子对骨骼肌卫星细胞的调控及其治疗作用。 方法：采用计算机检索中国期刊全文数据库及PubMed数据库1995/2009相关文献,中文检索词为“机械生长因子,骨骼肌卫星细胞”;英文检索词为“MGF”。纳入标准：具有原创性的研究论文,其研究目的或方法具有代表性。排除标准：重复性研究及与课题相关性较弱的文献。 结果与结论：机械生长因子有激活肌卫星细胞,促进细胞增殖,抑制肌管融合及促进卫星细胞迁移的功能。机械生长因子对骨骼肌损伤修复、神经损伤修复及心肌梗死治疗等方面有积极的临床意义。外源性机械生长因子类物质对肌组织修复、再生方面的作用,有可能为运动损伤的康复治疗开辟新的途径,并且对细胞移植具有一定的临床意义。     

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。     

骨骼肌卫星细胞生长因子与运动训练的关系

背景：大运动量训练可以导致骨骼肌组织微细结构的损伤性变化, 而骨骼肌卫星细胞的激活、增殖与分化和肌肉组织损伤的修复有密切关系。 目的：文章从训练导致肌肉组织结构性损伤需要修复的客观实际出发,提出运动后骨骼肌结构的修复与骨骼肌卫星细胞生长因子之间存在某种依赖关系。 方法：由第一作者通过计算机网络检索中国期刊全文数据库(CNKI)和Medline数据库(2000/2010),检索词分别为“骨骼肌卫星细胞,生长因子,运动训练,骨骼肌超微结构”和“Skeletal muscle satellite cells,exercise,growth factor”。 共检索到97篇文章,按纳入和排除标准对文献进行筛选,共纳入23篇文章。从运动后骨骼肌组织修复与骨骼肌卫星细胞生长因子的激活作用机制进行总结,对两者间的联系进行分析。 结果与结论：大强度训练可以导致骨骼肌组织的损伤,而卫星细胞是运动后恢复期骨骼肌修复的关键,其生长因子也与训练方式等因素有关。目前在骨骼肌卫星细胞的生长因子与运动训练之间的联系还缺乏足够的认识与研究。     

低氧训练对骨骼肌结构和功能的影响

背景：低氧训练配合运动训练来增加机体的缺氧程度，以调动体内的技能潜力，抵抗缺氧生理反应并积极适应，从而达到提高运动成绩的目的。 目的：总结低氧训练对骨骼肌结构和功能的影响，为低氧训练提供理论依据和指导作用。 方法：以“hypoxic training，skeletal muscle，function, structure”为检索词，检索PubMed数据库(1990/2009-03)；以“低氧训练、骨骼肌、功能、结构”为检索词，检索CNKI数据库(2000/2009-05)。文献检索语种限制为英文和中文。纳入低氧训练对骨骼肌结构和功能影响相关的内容，排除重复性研究。 结果与结论：计算机初检得到144篇文献，根据纳入排除标准，对文献进行分析。低氧训练避免传统高原训练所引起的弊端，可以根据机体的低氧适应能力，调节低氧环境，保证正常的训练，使骨骼肌获得有益的生理适应。与单纯的低氧刺激相比，不同的低氧形式刺激和不同的训练方法结合成为不同的低氧训练模式，对骨骼肌功能和结构的影响机制更为复杂。低氧训练对骨骼肌功能和结构的影响，主要在于低氧和训练的结合形式。实验的研究对象和测试方法的不同都有可能左右实验的结论，会影响低氧训练对骨骼肌作用的机制探讨。     

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.     

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.     

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.     

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.