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Augmentation of functional recovery via ROCK/PI3K/AKT pathway by Fasudil Hydrochloride in a rat sciatic nerve transection model.

BACKGROUNDS: The functional recovery after peripheral nerve injury remains unsatisfactory. This study aims to perform a comprehensive evalua … < 0.01). The wet weight ratio of the Gastrocnemius muscles and the area of the cross section of its myofibrils were greater in the Fasudil group (P < 0.01), which also demonstrated a higer ratio of axon-endplate connection and a larger size of endplates (P < 0.05). And there were no significant differences for the abovementioned parameters between the contro …

Total beta-adrenoceptor deficiency results in cardiac hypotrophy and negative inotropy.

The present study investigated cardiac function in hearts of mice with total deficiency of the beta1-, beta2- and beta3-adrenoceptors (TKO) in comparison to wildtype mice (WT). We investigated cardiac morphology and echocardiographic function, measured protein expression of Ca2+-regulatory proteins, SERCA 2a activity, myofibrillar function, and performed running wheel tests. Heart weight and heart-to-body weight ratio were significantly smaller in TKO as compared to WT. This was accompanied by a decrease in the size of the cardiomyocytes in TKO. Heart rate and ejection fraction were significan

Impact of neonatal asphyxia and hind limb immobilization on musculoskeletal tissues and S1 map organization: implications for cerebral palsy.

Cerebral palsy (CP) is a complex disorder of locomotion, posture and movements resulting from pre-, peri- or postnatal damage to the developing brain. In a previous study (Strata, F., Coq, J.O., Byl, N.N., Merzenich, M.M., 2004. Comparison between sensorimotor restriction and anoxia on gait and motor cortex organization: implications for a rodent model of cerebral palsy. Neuroscience 129, 141-156.), CP-like movement disorders were more reliably reproduced in rats by hind limb sensorimotor restriction (disuse) during development rather than perinatal asphyxia (PA). To gain new insights into the

Macrophagic myofasciitis: an emerging entity. Groupe d'Etudes et Recherche sur les Maladies Musculaires Acquises et Dysimmunitaires (GERMMAD) de l'Association Française contre les Myopathies (AFM).

BACKGROUND: An unusual inflammatory myopathy characterised by an infiltration of non-epithelioid histiocytic cells has been recorded with increasing frequency in the past 5 years in France. We reassessed some of these cases. METHODS: We did a retrospective analysis of 18 such cases seen in five myopathology centres between May, 1993, and December, 1997. The myopathological changes were reassessed at a clinopathology seminar. FINDINGS: Detailed clinical information was available for 14 patients. The main presumptive diagnoses were polymyositis and polymyalgia rheumatica. Symptoms included mya

Mechanisms of toxic cardiomyopathy.

BACKGROUND: Dilated cardiomyopathy is a frequent disease responsible for 40-50% of cases of heart failure. Idiopathic cardiomyopathy is a pr … rotein synthesis, decrease of contractile proteins and disproportion between the different types of myofibrils, changes in the regulation of myosin ATPase, up-regulation of the L-type calcium channels, increase of oxidative stress, and induction of ANP and p21 mRNA expression in ventricular myocardium. Metamfetamines: Catecholamine-mediated toxicity is the p …

Titin-based stiffening of muscle fibers in Ehlers-Danlos Syndrome.

OBJECTIVE: tenascin-X (TNX) is an extracellular matrix glycoprotein whose absence leads to Ehlers-Danlos Syndrome (EDS). TNX-deficient EDS patients present with joint hypermobility and muscle weakness attributable to increased compliance of the extracellular matrix. We hypothesized that in response to the increased compliance of the extracellular matrix in TNX-deficient EDS patients, intracellular adaptations take place in the elastic properties of the giant muscle protein titin. METHODS: we performed extensive single muscle fiber mechanical studies to determine active and passive properties

Effect of early low-intensity exercise on rat hind-limb muscles following acute ischemic stroke.

This study examined the effects of daily low-intensity exercise following acute stroke on mass, Type I and II fiber cross-sectional area, and myofibrillar protein content of hind-limb muscles in a rat model. Adult male Sprague-Dawley rats were randomly assigned to 1 of 4 groups (n = 7-9 per group): stroke (occlusion of the right middle cerebral artery [RMCA]), control (sham RMCA procedure), exercise, and stroke-exercise. Beginning 48 hours post-stroke induction/sham operation, rats in the exercise group had 6 sessions of exercise in which they ran on a treadmill at grade 10 for 20 min/day at 1

Short-term influences of lung volume reduction surgery on the diaphragm in emphysematous hamsters.

With emphysema, diaphragm length adaptation results in shortened fibers. We hypothesize that passive diaphragm stretch occurring acutely after lung volume reduction surgery (LVRS) results in fiber injury. Bilateral LVRS was performed in emphysematous hamsters. Studies were performed 1 (D1) and 4 (D4) days after LVRS, and compared with sham-treated groups. Sarcolemmal rupture was evident in 10.9% of fibers in LVRS-D1 and reduced to 1.6% in LVRS-D4. Ultrastructural analysis revealed focal abnormalities in both LVRS-D1 and LVRS-D4 animals in over one-third of fibers. Myofibrillar disruption was n

[Clinico-electrophysiologic effects of magnesium, especially in supraventricular tachycardia].

Clinical electrophysiological effects of magnesium (Mg2+) are known for more than 60 years. Mg2+ is a cation to be found ubiquitously in the … fects are closely linked. About 12% of cardiac Mg2+ is found in the mitochondria and 2 to 3% in the myofibrils. A large portion is incorporated in adenosin mono-, di- and triphosphate. Mg2+ affects intracellular calcium by inhibiting the influx of calcium into the myocyte through sarcolemmal channels, by modulation of cyclic AMP and by competing with calcium …

Knockout of p21-activated kinase-1 attenuates exercise-induced cardiac remodelling through altered calcineurin signalling.

AIMS: Despite its known cardiovascular benefits, the intracellular signalling mechanisms underlying physiological cardiac growth remain poorly understood. Therefore, the purpose of this study was to investigate a novel role of p21-activated kinase-1 (Pak1) in the regulation of exercise-induced cardiac hypertrophy. METHODS AND RESULTS: Wild-type (WT) and Pak1 KO mice were subjected to 6 weeks of treadmill endurance exercise training (ex-training). Cardiac function was assessed via echocardiography, in situ haemodynamics, and the pCa-force relations in skinned fibre preparations at baseline and

Novel Therapeutics for Anthracycline Induced Cardiotoxicity.

Anthracyclines remain an essential component of the treatment of many hematologic and solid organ malignancies, but has important implications on cardiovascular disease. Anthracycline induced cardiotoxicity (AIC) ranges from asymptomatic LV dysfunction to highly morbid end- stage heart failure. As cancer survivorship improves, the detection and treatment of AIC becomes more crucial to improve patient outcomes. Current treatment modalities for AIC have been largely extrapolated from treatment of conventional heart failure, but developing effective therapies specific to AIC is an area of growing

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… AIC on a cellular level is mediated by cytoplasmic vacuolization, cardiac fibrosis, and myofibril loss and is associated with echocardiographic of decreased systolic function, increased diastolic dysfunction, and decreased global longitudinal strain. … Cardiac samples obtained from autopsy of patients with AIC demonstrate necrotic cells within the ventricular wall, interstitial fibrosis, cytoplasmic vacuolization, and marked reduction in the number of cardiomyocytes and myofibrils ( 1 , 2 ). …

Loss of dystrophin expression in skeletal muscle is associated with senescence of macrophages and endothelial cells.

Cellular senescence is the irreversible arrest of normally dividing cells and is driven by cell cycle inhibitory proteins such as p16, p21, and p53. When cells enter senescence, they secrete a host of proinflammatory factors known as the senescence-associated secretory phenotype, which has deleterious effects on surrounding cells and tissues. Little is known of the role of senescence in Duchenne muscular dystrophy (DMD), the fatal X-linked neuromuscular disorder typified by chronic inflammation, extracellular matrix remodeling, and a progressive loss in muscle mass and function. Here, we demon

Arrhythmia-associated cardiac Ca²(+) cycling proteins and gene mutations.

Calcium is an important mediator in cardiac excitation and disorders in cardiac Ca(2+) homeostasis have great influence on the cardiac action potential. Therefore dysfunction in regulatory proteins that are involved in Ca(2+) handling can lead to the occurrence of severe arrhythmia. Although mutations in Ca(2+) regulating proteins are quite rare, they can offer general insights into arrhythmogenesis. Here, we briefly review some important aspects of arrhythmia-associated mutations in Ca(2+) regulating proteins with special emphasis to its associated pathophysiology.

Rosiglitazone-induced heart remodelling is associated with enhanced turnover of myofibrillar protein and mTOR activation.

We investigated cardiac hypertrophy elicited by rosiglitazone treatment at the level of protein synthesis/degradation, mTOR, MAPK and AMPK signalling pathways, cardiac function and aspects of carbohydrate/lipid metabolism. Hearts of rats treated or not with rosiglitazone (15 mg/kg day) for 21 days were evaluated for gene expression, protein synthesis, proteasome and calpain activities, signalling pathways, and function by echocardiography. Rosiglitazone induced eccentric heart hypertrophy associated with increased expression of ANP, BNP, collagen I and III and fibronectin, reduced heart rate a

Experimental Modeling Supports a Role for MyBP-HL as a Novel Myofilament Component in Arrhythmia and Dilated Cardiomyopathy.

BACKGROUND: Cardiomyopathy and arrhythmias are under significant genetic influence. Here, we studied a family with dilated cardiomyopathy and associated conduction system disease in whom prior clinical cardiac gene panel testing was unrevealing. METHODS: Whole-genome sequencing and induced pluripotent stem cells were used to examine a family with dilated cardiomyopathy and atrial and ventricular arrhythmias. We also characterized a mouse model with heterozygous and homozygous deletion of Mybphl. RESULTS: Whole-genome sequencing identified a premature stop codon, R255X, in the MYBPHL gene enc

Molecular Effects of cTnC DCM Mutations on Calcium Sensitivity and Myofilament Activation-An Integrated Multiscale Modeling Study.

Mutations in cardiac troponin C (D75Y, E59D, and G159D), a key regulatory protein of myofilament contraction, have been associated with dilated cardiomyopathy (DCM). Despite reports of altered myofilament function in these mutants, the underlying molecular alterations caused by these mutations remain elusive. Here we investigate in silico the intramolecular mechanisms by which these mutations affect myofilament contraction. On the basis of the location of cardiac troponin C (cTnC) mutations, we tested the hypothesis that intramolecular effects can explain the altered myofilament calcium sensit

N-acetylcysteine reverses diastolic dysfunction and hypertrophy in familial hypertrophic cardiomyopathy.

S-glutathionylation of cardiac myosin-binding protein C (cMyBP-C) induces Ca(2+) sensitization and a slowing of cross-bridge kinetics as a result of increased oxidative signaling. Although there is evidence for a role of oxidative stress in disorders associated with hypertrophic cardiomyopathy (HCM), this mechanism is not well understood. We investigated whether oxidative myofilament modifications may be in part responsible for diastolic dysfunction in HCM. We administered N-acetylcysteine (NAC) for 30 days to 1-mo-old wild-type mice and to transgenic mice expressing a mutant tropomyosin (Tm-E