The potential of obscurin as a therapeutic target in muscle disorders

Introduction: Obscurin, a giant protein of striated muscles, is emerging as an important player in a wide range of processes including myofibril assembly and maintenance, muscle protein degradation and intracellular signaling. Accordingly, obscurin participates to the mechanisms by which muscles adapt to physiological requirements or to pathological cues associated with cardiac and skeletal muscle diseases.

Areas covered: The structure of the different obscurin isoforms identified so far, their tissue distribution and the most recent findings on obscurin in invertebrates and mammals will be reviewed. We will provide a synopsis of known molecular interactions between obscurin and other proteins and the biological relevance of these interactions for striated muscle function. The involvement of obscurin in protein degradation mechanisms and intracellular signaling will be also discussed along with initial evidence of a role of obscurin in the pathophysiology of human diseases.

Expert opinion: Although still much remains to be discovered about the role of obscurin either as a structural component of the sarcomere or as a mediator of signaling pathways within muscle cells, it can be envisioned that this protein represents an interesting novel pharmacological target for the prevention and treatment of cardiac and skeletal muscle diseases.     

袖状胃切除术对肥胖合并2型糖尿病病人糖代谢和胃肠激素的影响

目的 探讨腹腔镜袖状胃切除术(LSG)对肥胖合并2型糖尿病病人糖代谢和胃肠激素的影响.方法 前瞻性收集2012年1月-2015年1月肥胖合并2型糖尿病病人80例,将病人按完全随机数字表原则随机分为LSG组和对照组,每组40例.主要观察指标为体质量指数(BMI)、血清糖化血红蛋白(HbA1C)、胰岛素、胰高血糖素样多肽-1(GLP-1)、肠抑胃肽(GIP)和胃泌素.结果 两组病人入院时BMI、HbA1C、胰岛素水平、GLP-1和胃泌素水平差异无统计学意义(P>0.05).但与对照组相比,治疗12个月后LSG组病人BMI显著降低[(25.48±2.49) kg·m-2 vs (29.49±2.48) kg·m-2,P<0.001)];HbA1C水平显著降低[(7.26±0.73)% vs (7.99±0.89)%,P<0.001)];胰岛素水平显著降低[(1.32±0.31) μg·L-1 vs (3.13±0.98) μg·L-1,P<0.001)];GLP-1水平显著升高[(39.85±13.56) μg·L-1 vs (12.58±5.32) μg·L-1,P<0.001];胃泌素水平显著降低[(17.46±7.46) μg·L-1 vs (34.73±11.49) μg·L-1,P<0.001].两组病人术前术后GIP水平均差异无统计学意义(P>0.05).结论 LSG对肥胖合并2型糖尿病病人糖代谢水平和胃肠激素影响显著.     

Oral Adenosine-5′-triphosphate (ATP) Administration Increases Postexercise ATP Levels,Muscle Excitability,and Athletic Performance Following a Repeated Sprint Bout

Objective: Oral adenosine-5′-triphosphate (ATP) administration has failed to increase plasma ATP levels; however, chronic supplementation with ATP has shown to increase power, strength, lean body mass, and blood flow in trained athletes. The purpose of this study was to investigate the effects of ATP supplementation on postexercise ATP levels and on muscle activation and excitability and power following a repeated sprint bout.

Methods: In a double-blind, placebo-controlled, randomized design, 42 healthy male individuals were given either 400 mg of ATP as disodium salt or placebo for 2 weeks prior to an exercise bout. During the exercise bout, muscle activation and excitability (ME, ratio of power output to muscle activation) and Wingate test peak power were measured during all sprints. ATP and metabolites were measured at baseline, after supplementation, and immediately following exercise.

Results: Oral ATP supplementation prevented a drop in ATP, adenosine-5′-diphosphate (ADP), and adenosine-5′-monophosphate (AMP) levels postexercise (p < 0.05). No group by time interaction was observed for muscle activation. Following the supplementation period, muscle excitability significantly decreased in later bouts 8, 9, and 10 in the placebo group (?30.5, ?28.3, and ?27.9%, respectively; p < 0.02), whereas ATP supplementation prevented the decline in later bouts. ATP significantly increased Wingate peak power in later bouts compared to baseline (bout 8: +18.3%, bout 10: +16.3%).

Conclusions: Oral ATP administration prevents exercise-induced declines in ATP and its metabolite and enhances peak power and muscular excitability, which may be beneficial for sports requiring repeated high-intensity sprinting bouts.     

Neurogenic muscle hypertrophy

Summary Muscle hypertrophy is rare in denervating diseases. A patient with calf enlargement associated with L5–S1 radiculopathy and another with thenar, hypothenar, forearm and calf muscle hypertrophy in the course of chronic relapsing inflammatory demyelinating polyneuropathy are described. Gastrocnemius muscle biopsy revealed both type I and type II fibre hypertrophy in the former case and predominant type I fibre hypertrophy in the latter. Passive stretching and abnormal spontaneous muscular activity might have played a role in the origin of hypertrophy in both patients, but a satisfactory explanation for denervation hypertrophy has yet to be provided.     

Evidence for a chronic axonal atrophy in oculopharyngeal “muscular dystrophy”

Summary We report on morphometric investigations of peripheral nerves in a woman, who died at the age of 69, presenting the classical symptoms of oculopharyngeal muscular dystrophy (OPMD) and a typical family history with several members (males and females) affected over three generations.Evidence for chronic axonal atrophy was found in peripheral nerves and especially in oculomotor nerves with severe axon loss in endomysial nervetwigs of extra-ocular, laryngeal, and tongue muscles. Whereas limb muscles presented features of neurogenic atrophy, severe changes of myopathic type were evident in extrinsic eye muscles, laryngeal constrictor, tongue, and diaphragma. However, we interpreted these changes as neurogenic in origin in view of the severe denervation found in those muscles. Our findings suggest that OPMD is a disease of primary neurogenic origin rather than a primary myopathic disorder.     

带血管腓骨干切取应用解剖的几点补充

目的:为临床带血管腓骨干切取补充解剖学基础。方法:在24侧防腐固定的成年小腿标本上,将腓骨全长平均分为4段,解剖观测腓骨肌肉的附着及部分肌肉的神经支配情况,观测腓骨营养血管的起始位置的特征。结果:腓骨干上附着肌肉的宽度从大到小依次为腓骨肌面、屈肌面、胫骨后肌面和伸肌面。腓骨短肌的肌支发出处距腓骨头尖(9.9±2.7)cm,于腓骨中2/4段和中3/4段的上半部分最贴近腓骨骨面,长伸肌的第1肌支起始位置距腓骨头尖(10.1±1.9)cm,于腓骨的中2/4段紧贴腓骨前缘,腓骨滋养动脉和第1￣3弓状动脉集中于腓骨中2/4段。结论:(1)带血管腓骨干所可能切取的“肌袖”主要为长屈肌和胫骨后肌;(2)腓骨肌面的中2/4段和中3/4段的上半部分为手术时容易损伤腓骨短肌肌支的部位;(3)腓骨中2/4段近腓骨前缘是长伸肌神经支最易损伤的部位;(4)近端截骨点位于腓骨上1/4段中点的切取可以最大程度地包含腓骨的营养血管。     

人和哺乳动物比目鱼肌的纤维型

采用Ａｃｈｌａｓ氏法对成年人和大鼠、小鼠、家兔、豚鼠及犬的比目鱼肌纤维类型进行了研究。结果表明：人类和哺乳动力动物的比目鱼肌纤维均可分为两种类型。Ｉ型纤维中线粒体含量高，琥珀酸脱氢酶活性也高，但其直径小。ＩＩ型纤维中线粒体含量和琥珀酸脱氢酶活性均低，而其直径大。可以认为，人类和哺乳动物的比目鱼肌纤维并非同质。     

Electrical impedance in the lower limbs of patients with Duchenne muscular dystrophy: A preliminary study

Electrical impedances were measured, at a range of frequencies from 2 to 200 kHz, in the lower limbs of nine patients with Duchenne muscular dystrophy and 12 normal subjects. The specific admittance was calculated from the impedance, based on the assumption that the shape of the part of the limb measured is a truncated cone. Curve-fitting to the admittance locus on the complex plane gave the intracellular and extracellular resistances and the membrane capacitance. The intracellular resistance was higher and the membrane capacitance was lower in the patients than in the normal subjects. The membrane capacitance in the normal subjects increased with age. In the patients, the membrane capacitance decreased, and the intracellular resistance increased with the stage of disability, which was assessed by a physician. These experimental results agree well with the theoretical explanation, which uses simplified spherical models to represent living tissue.     

Dystrophin negative skeletal and myocardial muscle cells in a carrier of Duchenne's muscular dystrophy

A 47-year-old woman whose elder son had typical Duchenne's musculardystrophy (DMD) was diagnosed as the manifesting carrier ofthe disease. She had developed congestive heart failure buthad no evidence of skeletal muscular atrophy. Histological observationof the cardiac muscle revealed a mosaic pattern of dystrophinnegative fibres detected by immunofluorescence analysis.