消瘿强肌汤对甲状腺机能亢进性肌病骨骼肌线粒体的影响

目的观察消瘿强肌汤对甲状腺机能亢进性肌病大鼠骨骼肌线粒体的影响,探讨消瘿强肌汤治疗甲亢肌病的机理。方法健康雌性Wistar大鼠随机分为4组：甲亢肌病模型组每日腹腔注射甲状腺激素钠盐250μg/100g造模,中药组在造模后灌服消瘿强肌汤30d,生理盐水对照组造模后灌服生理盐水30d,正常对照组每天腹腔注射生理盐水。各组取骨骼肌观察琥珀酸脱氢酶活性和含量的变化,透射电镜观察骨骼肌及线粒体的形态变化。结果甲亢肌病模型组骨骼肌琥珀酸脱氢酶呈色降低,含量下降。超微结构显示线粒体嵴断裂,甚至融合消失。中药组可见酶活性和含量恢复,线粒体嵴排列规则,空泡消失。结论消瘿强肌汤可通过恢复线粒体酶活性和线粒体结构来改善甲亢肌病的骨骼肌功能。     

Prophylactic implantable cardioverter defibrillator placement in a sporadic desmin related myopathy and cardiomyopathy

Desminopathy is a neuromuscular disorder associated with the accumulation of the protein desmin. This article reports a case of a man with a mutation in the desmin gene suffering from cardiomyopathy and skeletal myopathy. This patient underwent implantable cardioverter defibrillator (ICD) implantation for prognostic considerations and subsequently developed a sustained ventricular tachycardia (SVT). While nonsustained VTs (NSVT) have previously been reported, this is the first time that a SVT could be seen in a patient with this disease.     

Nemaline myopathy with dilated cardiomyopathy and severe heart failure: A case report

BACKGROUNDNemaline myopathy (NM) is a rare type of congenital myopathy, with an incidence of 1:50000. Patients with NM often exhibit hypomyotonia and varying degrees of muscle weakness. Skeletal muscles are always affected by this disease, while myocardial involvement is uncommon. However, with improvements in genetic testing technology, it has been found that NM with a mutation in the myopalladin (MYPN) gene not only causes slow, progressive muscle weakness but also results in dilated or hypertrophic cardiomyopathy.CASE SUMMARYA 3-year-old pre-school boy was admitted to our hospital with cough, edema, tachypnea, and an increased heart rate. The patient was clinically diagnosed with severe dilated cardiomyopathy and heart failure, and subsequent gene examination confirmed the diagnosis of NM with a mutation in MYPN. Captopril, diuretics, low-dose digoxin, and dobutamine were administered. After 22 d of hospitalization, the patient was discharged due to the improvement of clinical symptoms. During the follow-up period, the patient died of refractory heart failure.CONCLUSIONDecreased muscular tone and dilated cardiomyopathy are common features of MYPN-mutated NM. Heart transplantation may be a solution to this type of cardiomyopathy.     

酒精性心肌病的超声诊断

本文对50例过量饮酒者观察中发现：其人室心肌内多有散在异常斑点状回声。该征象在伴有左心功能异常的饮酒者中检出85．7％，而相应功能正常的饮酒者中仅为37．5％（P＜0．05），无饮酒史的对照组中则无此表现。乙醇摄入总量与左室肥厚程度呈正相关（r＝0．48，P＜0．01）。依据心肌异常声学特征．结合慢性过量饮酒史以及超声上左室肥厚、内膜心肌纤维化和减低的左室射血分数，则超声可对酒精性心肌病（ACM）作出诊断。     

Cellular energetics in hypothyroid muscle

Skeletal muscle of seven hypothyroid patients was investigated in the resting state and during exercise and recovery using 31P magnetic resonance spectroscopy. The bioenergetics and intracellular pH of the hypothyroid muscle were thus evaluated and compared with results from normal muscle and muscle of patients with mitochondrial myopathy. In resting hypothyroid muscle there were significant elevations in the concentration ratios of phosphocreatine/ATP and inorganic phosphate/ATP, while phosphocreatine/inorganic phosphate and intracellular pH were lower than normal. In exercising hypothyroid muscle, energy stores were depleted more rapidly and acidification began later than in normal muscle. Recovery of phosphocreatine to the pre-exercise value was normal, but intracellular pH recovered slowly. The data suggest that in the hypothyroid state, glycogen breakdown in skeletal muscle was delayed thereby limiting the substrate supply for both glycolytic and oxidative production of ATP at the beginning of exercise. There was no evidence for a decrease in the oxidative capacity of the muscle of our patients, but elevated ADP may have stimulated oxidative metabolism and helped to compensate for low mitochondrial content. The low intracellular pH in resting muscle and the slow pH recovery after exercise imply that proton handling was abnormal in the hypothyroid muscle.     

骨骼肌细胞损伤致延迟性肌肉酸痛：如何有效提高损伤肌肉恢复的速度和质量

背景：目前临床尚缺乏一种简单有效的防治延迟性肌肉酸痛的方法。目的：查阅国内外有关骨骼肌损伤及修复的相关文献,归纳总结延迟性肌肉酸痛的损伤机制和治疗方法。方法：检索1991年1月至2014年1月万方医学网和PubMed数据库的文献。英文检索词包括＂molecular mechanisms;delayed onset muscle sorenes;pain;skeletal muscle＂;中文检索词包括＂骨骼肌;损伤;延迟性肌肉酸痛;分子机制＂。纳入与骨骼肌形态结构、延迟性肌肉酸痛机制、骨骼肌治疗和修复的相关研究,阅读全文对24篇文献进行归纳分析。结果与结论：研究表明,骨骼肌损伤与钙失调、能量失调及高浓度的活性氧有关。骨骼肌性损伤包括代谢损伤、机械损伤和炎症损伤。胰岛素样生长因子、过氧化物酶体增殖物激活受体γ辅激活子1α及肿瘤坏死因子α在骨骼肌修复过程中均发挥重要作用。动物实验表明依达拉奉通过直接阻止骨骼肌中自由基的快速过氧化损伤,减少二次损伤和炎症的浸润。临床研究表明中药制剂、按摩、针灸可以延缓运动性肌肉损伤和疲劳的发生,有效提高损伤肌肉恢复的速度和质量;将理疗与中药相结合治疗延迟性肌肉酸痛可达到满意效果。     

Protein adducts in type I and type II fibre predominant muscles of the ethanol-fed rat: preferential localisation in the sarcolemmal and subsarcolemmal region

BACKGROUND: Chronic alcoholic myopathy is characterised by reduced muscle strength and structural changes including a decrease in the diameter of Type II (glycolytic, fast-twitch, anaerobic) fibres. In contrast, the Type I fibres (oxidative, slow-twitch, aerobic) are relatively protected. It is possible that adduct formation with reactive metabolites of ethanol may be a contributory process. MATERIALS AND METHODS: We analysed skeletal muscles from rats fed nutritional-complete liquid diets containing ethanol as 35% of total dietary energy; control rats were fed the same diet in which ethanol was replaced by isocaloric glucose. Reduced-acetaldehyde, unreduced-acetaldehyde, malondialdehyde, malondialdehyde-acetaldehyde and alpha-hydroxyethyl protein-adducts in both soleus and plantaris were analysed by ELISA or immunohistochemistry with comparative studies in liver. RESULTS: After 6 weeks, the weights of the plantaris, but not the soleus, were decreased. ELISA analyses for protein adducts showed increased amounts of unreduced-acetaldehyde adducts in soleus (P < 0.025) and plantaris (P < 0.025). Reduced-acetaldehyde, malondialdehyde, malondialdehyde-acetaldehyde and alpha-hydroxyethyl protein-adducts in both soleus and plantaris muscles from ethanol-fed rats were not significantly different from their pair-fed controls (P > 0.05). In contrast, liver from ethanol-fed rats showed significantly higher levels of unreduced-acetaldehyde (P < 0.025), reduced-acetaldehyde (P < 0.01), malondialdehyde (P < 0.01), malondialdehyde-acetaldehyde (P < 0.025) and alpha-hydroxyethyl radical (P < 0.01) protein adducts compared to pair-fed controls. Immuno-histochemical analysis using an antiserum reacting with both reduced- and unreduced-acetaldehyde adducts showed adducts were increased in soleus (P < 0.05) and plantaris (P < 0.025), confirming ELISA analysis. Adducts were located within the sarcolemmal (i.e. muscle membrane) and subsarcolemmal regions. CONCLUSION: This is the first report of adduct formation in myopathic skeletal muscle due to chronic alcohol ingestion and suggests a role for acetaldehyde in the aetiology of alcoholic myopathy.     

两家系扩张型心肌病的超声心动图特征

目的　阐述两家系扩张型心肌病的超声心动图 (UCG)特征。方法　应用UCG检查发现两家系扩张型心肌病并经X线影像证实其诊断。结果　第一家系 1 2口人的UCG检查表现左房、右室增大者 4例。第二家系 9口人的UCG检查表现单纯左房增大者 5例。结论　超声心动图检查如发现不明原因的心脏某腔室增大 ,在鉴别诊断中应想到家族性扩张型心肌病的可能 ,应进行医学家系调查     

Correlation of Electrophysiological Activation Patterns to Tension Generation in Stimulated Latissimus Dorsi Muscle

Skeletal muscle has been used for biomechanical assist in experimental and clinical studies. Central to the success of these procedures is the generation of sufficient muscle force for the lifetime of the subject. Burst (tetanic) stimulation results in summation of individual twitches and generates higher power output. However, the superiority of paraneural versus intramuscular as well as proximal versus middle and distal intramuscular stimulations remains unclear. Electrophysiological mapping and mechanical performance of seven canine latissimus dorsi muscles were analyzed. The mechanism of higher tension generation produced by: (1) increased temporal summation; (2) greater motor units activated; or (3) result of both were determined. The parameters primarily dependent on the number of activated motor units are significantly greater following paraneural and proximal intramuscular stimulations. The parameters mainly related to temporal summation are not different between various electrode configurations. For intramuscular stimulation, it is the location of interelectrode field rather than the location of the cathode perse that determines the mechanical performance of the skeletal muscle. Furthermore, tension development of skeletal muscle is primary nerve activation rather than direct muscle stimulation. The higher tension generation that resulted from different electrode configurations is produced by activating a higher number of muscle fibers through the neuromuscular junctions.     

Different expressions of X-linked cardiomyopathy in monozygotic triplets with Becker's dystrophy

Cardiac involvement is common in skeletal muscles disorders associated with dystrophin defect. It has been suggested however, that X-linked dilated cardiomyopathies with minimal or absent skeletal disease are distinct entities, resulting from mutations in cardiac-specific regions of dystrophin gene. This study presents a unique observation of phenotypic variability in monozygotic triplets with Becker's muscular dystrophy. The expressions of the disease range from severe peripheral myopathy to severe congestive heart failure. No deletion in dystrophin gene was observed and the mechanisms responsible for selective impairment of morphologically and functionally different muscles in three monozygotic siblings remain unclear.     

Incessant Fascicular Tachycardia: A Cause of Arrhythmia Induced Cardiomyopathy

An incessant ventricular tachycardia arising from the posterior fascicle is reported in a 29-yearold woman. This fascicular tachycardia was due to triggered activity and was clinically induced by an underlying paroxysmal atrial fibrillation. The initial echocardiographic evaluation revealed biventricular dysfunction with an ejection fraction of 30%. On propranolol, the patient has remained asymptomatic and the ventricular function has become normal after 3 months free of arrhythmia.     

Morphological, electrophysiological, and metabolic characteristics of skeletal muscle in people with end-stage renal disease: a critical review

Purpose: Fatigue is one of the most frequent debilitating symptoms reported by people with end-stage renal disease (ESRD) on haemodialysis (HD) therapy. A wide range of underlying abnormalities, including skeletal muscle weakness, have been implicated as causes of this fatigue. Skeletal muscle weakness is well established in this population, and such muscle weakness is amenable to physical therapy treatment. The purpose of this review was to identify morphological, electrophysiological, and metabolic characteristics of skeletal muscles in people with ESRD/HD that may cause skeletal muscle weakness.Method: Electronic databases were searched for relevant literature from inception to March 2010. Inclusion criteria were English language; adult subjects with ESRD/HD; and the use of muscle biopsy, electromyography, and nuclear magnetic spectroscopy ((31)P-NMRS) techniques to evaluate muscle characteristics.Results: In total, 38 studies were included. All studies of morphological characteristics reported type II fibre atrophy. Electrophysiological characteristics included both neuropathic and myopathic skeletal muscle changes. Studies of metabolic characteristics revealed higher cytosolic inorganic phosphate levels and reduced effective muscle mass.Conclusion: The results indicate an array of changes in the morphological, electrophysiological, and metabolic characteristics of skeletal muscle structure in people with ESRD/HD that may lead to muscle weakness.     

Renin‐Angiotensin System: An Old Player with Novel Functions in Skeletal Muscle

Skeletal muscle is a tissue that shows the most plasticity in the body; it can change in response to physiological and pathological stimuli. Among the diseases that affect skeletal muscle are myopathy‐associated fibrosis, insulin resistance, and muscle atrophy. A common factor in these pathologies is the participation of the renin‐angiotensin system (RAS). This system can be functionally separated into the classical and nonclassical RAS axis. The main components of the classical RAS pathway are angiotensin‐converting enzyme (ACE), angiotensin II (Ang‐II), and Ang‐II receptors (AT receptors), whereas the nonclassical axis is composed of ACE2, angiotensin 1–7 [Ang (1–7)], and the Mas receptor. Hyperactivity of the classical axis in skeletal muscle has been associated with insulin resistance, atrophy, and fibrosis. In contrast, current evidence supports the action of the nonclassical RAS as a counter‐regulator axis of the classical RAS pathway in skeletal muscle. In this review, we describe the mechanisms involved in the pathological effects of the classical RAS, advances in the use of pharmacological molecules to inhibit this axis, and the beneficial effects of stimulation of the nonclassical RAS pathway on insulin resistance, atrophy, and fibrosis in skeletal muscle.     

抗HMGCR/SRP抗体阳性的特发性炎性肌病特点分析

目的:探讨抗HMGCR/SRP抗体阳性的特发性炎性肌病(IIM)的临床和病理特点。方法:收集HMGCR/SRP抗体阳性的IIM患者5例,对其危险因素、临床表现、实验室检查、肌电图、肌肉MRI、肌肉病理、肌炎自身抗体及药物治疗进行分析。结果:抗HMGCR/SRP抗体阳性的IIM患者临床变异较大,但大多有肌肉无力;血清肌酸激酶均较高;5例患者肌电图均表现为典型的肌源性损害。肌肉MRI主要表现为肌肉水肿。3例为典型坏死性肌病表现,1例镜下偶见肌细胞坏死,1例为多发性肌炎表现。HMGCR抗体阳性患者其中1例为正服用他汀药物,另一患者服用抗精神病药物;SRP抗体阳性患者1例为自身免疫性疾病患者,1例长期服用他汀,另1例病因未明确。激素治疗效果不一,2例加用丙种球蛋白治疗,1例加用免疫抑制剂治疗。结论:抗HMGCR/SRP抗体阳性的IIM临床表现各异,肌电图仅能定位肌肉损害,主要依靠肌肉活检,肌炎自身抗体检查更有助于诊断和具体分型,疗效各型不一。     

High Incidence of Sudden Death with Conduction System and Myocardial Disease Due to Lamins A and C Gene Mutation

BÉCANE, H.–M., et al. : High Incidence of Sudden Death with Conduction System and Myocardial Disease Due to Lamins A and C Gene Mutation. We studied 54 living relatives from a large French kindred, among which 17 members presented with a cardiomyopathy transmitted on an autosomal dominant mode. Five of these individuals had clinical manifestations of muscle disease phenotypically consistent with Emery-Dreifuss muscular dystrophy. Genetic analysis of this kindred had demonstrated a nonsense mutation in the LMNA gene located on chromosome 1q11–q23. This gene encodes lamins A and C, proteins of the nuclear lamina located on the inner face of the nuclear envelope. We retrospectively determined the cause of death of 15 deceased family members, 8 of whom had died suddenly, 2 as a first and single manifestation of the disease. The six other cases had histories of arrhythmias and left ventricular dysfunction before dying suddenly, and three of them died despite the prior implantation of a permanent pacemaker. The mean age of onset of cardiac symptoms among affected living family members was 33 years (range 15–47 years), and the first symptoms were due to marked atrioventricular conduction defects or sinus dysfunction, requiring the implantation of permanent pacemakers in seven cases. Myocardial dysfunction accompanied by ventricular arrhythmias developed rapidly in the course of the disease and resulted in severe dilated cardiomyopathy requiring cardiac transplantation in three cases. In conclusion, in patients presenting a life-threatening familial or sporadic cardiac restricted phenotype similar to that described here, mutations in the lamins A and C gene should be looked for. In the genotypically affected individuals, cardiological and electrophysiological follow-up should be performed to prevent sudden death that could occur rapidly in the evolution of such disease.     

Myasthenia gravis and steroid-induced myopathy of the respiratory muscles

Objective: We report a case of corticosteroid-induced myopathy with involvement of respiratory muscles observed in a myasthenic patient.Patient: A 37-years-old woman, under corticosteroid treatment for two years for typical myasthenia gravis was admitted to ICU for acute myasthenic respiratory failure. Weaning from mechanical ventilation remained impossible despite 4 plasma exchanges and azathioprin. The patient exhibited a progressive 12kg weight loss with muscular weakness and atrophy.Measurements and results: Peripheral and diaphragmatic electromyography as well as histological study were consistent with a steroid-induced myopathy. Discontinuation of corticosteroid treatment was followed by a rapid weight gain with general improvement and allowed weaning from mechanical ventilation with a complete recovery.Conclusion: This case provides evidence that corticosteroid-induced myopathy may be observed in myasthenia gravis and may involve the respiratory muscles as well as the peripheral musculature.     

Sudden Death Due to Atrial Fibrillation in Hypertrophic Cardiomyopathy:

FAVALE, S., et al .: Sudden Death Due to Atrial Fibrillation in Hypertrophic Cardiomyopathy: A Predictable Event in a Young Patient. This case refers to a 39-year-old woman with hypertrophic cardiomyopathy (HCM) and family history of sudden death (SD). In 1985, high rate atrial stimulation induced VF. In 1996 an ICD was implanted and she remained without arrhythmic events until November 2000 when the device reported one episode of atrial fibrillation degenerating into VF and terminated by the ICD. The VF induction mechanism recorded by the ICD was similar to that observed in 1985. The high incidence of atrial tachyarrhythmias in HCM renders cases like this at higher risk of SD. The predictive role of incremental atrial stimulation merits highlighting in future studies. (PACE 2003; 26[Pt. I]:637–639)     

伴肌纤维坏死的脂质沉积性肌病8例临床与肌肉病理分析

目的探讨伴有肌纤维坏死的脂质沉积性肌病患者的骨骼肌病理改变及其临床特点。方法回顾性分析8例伴有肌纤维坏死的脂质沉积性肌病患者的肌肉组织病理改变和临床特点。结果 8例患者中上肢近端肌力3级以下者4例(其中2例伴呼吸肌受累),下肢近端肌力3级以下者6例;8例均伴有颈伸肌无力;8例患者除肌纤维内大量脂质沉积外,均伴有不同程度肌纤维变性坏死,其中5例偶见变性坏死肌纤维,坏死肌纤维比率0.1%~0.9%,病程较长且年龄偏大,有反复出现肌无力的病史;3例可见较多变性坏死纤维,坏死肌纤维比率>1.0%,病程较短、进展迅速且较年轻,其中2例免疫组织化学结果显示CD4(-)、CD8(-)、CD20(-)、CD68(+);3例基因检测显示ETFDH基因突变。结论部分脂质沉积性肌病患者的肌肉病理中可见变性坏死肌纤维,伴有明显肌纤维坏死者临床症状较重,病情进展较快。     

Long-Term Neurostimulation of Skeletal Muscle: Its Potential for a Tether-Free Biologic Cardiac Assist Device

Skeletal muscle has a tremendous capacity to adapt. This adaptive phenomenon is seen perhaps to the greatest extent when skeletal muscle is subjected to chronic low frequency stimulation via the motor nerve. There is a decrease in glycolytic enzymes and an increase in oxidotive enzymes, as well as a change in the contractile proteins and an increase in the mitochondrial volume fraction of the muscle fiber. These adaptive changes result in a muscle that is considerably more fatigue-resistant. Specifically herein, we report on a pneumatic aortic counterpulsator device powered by skeletal muscle. These muscle pumps functioned continuously and pumped blood effectively in tether-free animals for several weeks.     

Myotubularin controls desmin intermediate filament architecture and mitochondrial dynamics in human and mouse skeletal muscle

Muscle contraction relies on a highly organized intracellular network of membrane organelles and cytoskeleton proteins. Among the latter are the intermediate filaments (IFs), a large family of proteins mutated in more than 30 human diseases. For example, mutations in the DES gene, which encodes the IF desmin, lead to desmin-related myopathy and cardiomyopathy. Here, we demonstrate that myotubularin (MTM1), which is mutated in individuals with X-linked centronuclear myopathy (XLCNM; also known as myotubular myopathy), is a desmin-binding protein and provide evidence for direct regulation of desmin by MTM1 in vitro and in vivo. XLCNM-causing mutations in MTM1 disrupted the MTM1-desmin complex, resulting in abnormal IF assembly and architecture in muscle cells and both mouse and human skeletal muscles. Adeno-associated virus-mediated ectopic expression of WT MTM1 in Mtm1-KO muscle reestablished normal desmin expression and localization. In addition, decreased MTM1 expression and XLCNM-causing mutations induced abnormal mitochondrial positioning, shape, dynamics, and function. We therefore conclude that MTM1 is a major regulator of both the desmin cytoskeleton and mitochondria homeostasis, specifically in skeletal muscle. Defects in IF stabilization and mitochondrial dynamics appear as common physiopathological features of centronuclear myopathies and desmin-related myopathies.