Sample records for abnormal muscular coupling

  1. An explorative, cross-sectional study into abnormal muscular coupling during reach in chronic stroke patients

    PubMed Central

    2010-01-01

    Background In many stroke patients arm function is limited, which can be related to an abnormal coupling between shoulder and elbow joints. The extent to which this can be translated to activities of daily life (ADL), in terms of muscle activation during ADL-like movements, is rather unknown. Therefore, the present study examined the occurrence of abnormal coupling on functional, ADL-like reaching movements of chronic stroke patients by comparison with healthy persons. Methods Upward multi-joint reaching movements (20 repetitions at a self-selected speed to resemble ADL) were compared in two conditions: once facilitated by arm weight compensation and once resisted to provoke a potential abnormal coupling. Changes in movement performance (joint angles) and muscle activation (amplitude of activity and co-activation) between conditions were compared between healthy persons and stroke patients using a repeated measures ANOVA. Results The present study showed slight changes in joint excursion and muscle activation of stroke patients due to shoulder elevation resistance during functional reach. Remarkably, in healthy persons similar changes were observed. Even the results of a sub-group of the more impaired stroke patients did not point to an abnormal coupling between shoulder elevation and elbow flexion during functional reach. Conclusions The present findings suggest that in mildly and moderately affected chronic stroke patients ADL-like arm movements are not substantially affected by abnormal synergistic coupling. In this case, it is implied that other major contributors to limitations in functional use of the arm should be identified and targeted individually in rehabilitation, to improve use of the arm in activities of daily living. PMID:20233402

  2. Abnormal sympathetic innervation of the heart in a patient with Emery-Dreifuss muscular dystrophy.

    PubMed

    Fujiita, Takashi; Shimizu, Masami; Kaku, Bunji; Kanaya, Hounin; Horita, Yuki; Uno, Yoshihide; Yamazaki, Tsukasa; Ohka, Takio; Sakata, Kenji; Mabuchi, Hiroshi

    2005-07-01

    A 33-year-old man was admitted for general malaise and vomiting. An electrocardiogram showed a complete atrioventricular block and an echocardiogram showed right atrial dilatation and normal wall motion of left ventricle (LV). Gene analysis showed nonsense mutation in the STA gene, which codes for emerin, and Emery-Dreifuss muscular dystrophy was diagnosed. An endomyocardial biopsy of right ventricle showed mild hypertrophy of myocytes. Myocardial scintigraphic studies with Tc-99m methoxyisobutylisonitrile (MIBI) and I-123-betamethyl-p-iodophenylpentadecanoic acid (BMIPP) scintigrams showed no abnormalities. In contrast, I-123 metaiodobenzylguanidine (MIBG) scintigrams showed a diffuse and severe decrease in accumulation of MIBG in the heart. Six months later, his LV wall motion on echocardiograms developed diffuse hypokinesis. These results suggest that the abnormality on I-123 MIBG myocardial scintigrams may predict LV dysfunction in Emery-Dreifuss muscular dystrophy.

  3. Possible influences on the expression of X chromosome-linked dystrophin abnormalities by heterozygosity for autosomal recessive Fukuyama congenital muscular dystrophy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Beggs, A.H.; Neumann, P.E.; Anderson, M.S.

    1992-01-15

    Abnormalities of dystrophin, a cytoskeletal protein of muscle and nerve, are generally considered specific for Duchenne and Becker muscular dystrophy. However, several patients have recently been identified with dystrophin deficiency who, before dystrophin testing, were considered to have Fukuyama congenital muscular dystrophy (FCMD) on the basis of clinical findings. Epidemiologic data suggest that only 1/3,500 males with autosomal recessive FCMD should have abnormal dystrophin. To explain the observation of 3/23 FCMD males with abnormal dystrophin, the authors propose that dystrophin and the FCMD gene product interact and that the earlier onset and greater severity of these patients' phenotype (relative tomore » Duchenne muscular dystrophy) are due to their being heterozygous for the FCMD mutation in addition to being hemizygous for Duchenne muscular dystrophy, a genotype that is predicted to occur in 1/175,000 Japanese males. This model may help explain the genetic basis for some of the clinical and pathological variability seen among patients with FCMD, and it has potential implications for understanding the inheritance of other autosomal recessive disorders in general. For example, sex ratios for rare autosomal recessive disorders caused by mutations in proteins that interact with X chromosome-linked gene products may display predictable deviation from 1:1.« less

  4. Muscular Dystrophy

    MedlinePlus

    ... Gardner-Medwin D. Variability in clinical, genetic and protein abnormalities in manifesting carriers of Duchenne and Becker muscular dystrophy . Neuromuscul. Disord. Jan 1993;3(1):57-64. 3. Bushby KM, Appleton R, Anderson ...

  5. Autonomic, locomotor and cardiac abnormalities in a mouse model of muscular dystrophy: targeting the renin-angiotensin system.

    PubMed

    Sabharwal, Rasna; Chapleau, Mark W

    2014-04-01

    New Findings What is the topic of this review? This symposium report summarizes autonomic, cardiac and skeletal muscle abnormalities in sarcoglycan-δ-deficient mice (Sgcd-/-), a mouse model of limb girdle muscular dystrophy, with emphasis on the roles of autonomic dysregulation and activation of the renin-angiotensin system at a young age. What advances does it highlight? The contributions of the autonomic nervous system and the renin-angiotensin system to the pathogenesis of muscular dystrophy are highlighted. Results demonstrate that autonomic dysregulation precedes and predicts later development of cardiac dysfunction in Sgcd-/- mice and that treatment of young Sgcd-/- mice with the angiotensin type 1 receptor antagonist losartan or with angiotensin-(1-7) abrogates the autonomic dysregulation, attenuates skeletal muscle pathology and increases spontaneous locomotor activity. Muscular dystrophies are a heterogeneous group of genetic muscle diseases characterized by muscle weakness and atrophy. Mutations in sarcoglycans and other subunits of the dystrophin-glycoprotein complex cause muscular dystrophy and dilated cardiomyopathy in animals and humans. Aberrant autonomic signalling is recognized in a variety of neuromuscular disorders. We hypothesized that activation of the renin-angiotensin system contributes to skeletal muscle and autonomic dysfunction in mice deficient in the sarcoglycan-δ (Sgcd) gene at a young age and that this early autonomic dysfunction contributes to the later development of left ventricular (LV) dysfunction and increased mortality. We demonstrated that young Sgcd-/- mice exhibit histopathological features of skeletal muscle dystrophy, decreased locomotor activity and severe autonomic dysregulation, but normal LV function. Autonomic regulation continued to deteriorate in Sgcd-/- mice with age and was accompanied by LV dysfunction and dilated cardiomyopathy at older ages. Autonomic dysregulation at a young age predicted later development of

  6. Cervical neuro-muscular syndrome: discovery of a new disease group caused by abnormalities in the cervical muscles.

    PubMed

    Matsui, Takayoshi; Ii, Kunio; Hojo, Shuntaro; Sano, Keiji

    2012-01-01

    Our previous study of whiplash injury found that abnormalities in the cervical muscles cause autonomic dystonia. Further research has found that abnormalities in the cervical muscles cause headache, chronic fatigue syndrome, vertigo, and dizziness. We named this group of diseases cervical neuro-muscular syndrome. Patients treated within a 2-year period from April 1, 2002 to March 31, 2004 reported good outcomes in 83.8% for headache, 88.4% for vertigo and dizziness, 84.5% for chronic fatigue syndrome, 88.0% for autonomic dystonia, and 83.7% for whiplash-associated disorder. A large number of outpatients present with general malaise, including many general physical complaints without identifiable cause. We propose that treatment of the cervical muscle is effective for general malaise.

  7. Becker muscular dystrophy-like myopathy regarded as so-called "fatty muscular dystrophy" in a pig: a case report and its diagnostic method.

    PubMed

    Horiuchi, Noriyuki; Aihara, Naoyuki; Mizutani, Hiroshi; Kousaka, Shinichi; Nagafuchi, Tsuneyuki; Ochiai, Mariko; Ochiai, Kazuhiko; Kobayashi, Yoshiyasu; Furuoka, Hidefumi; Asai, Tetsuo; Oishi, Koji

    2014-03-01

    We describe a case of human Becker muscular dystrophy (BMD)-like myopathy that was characterized by the declined stainability of dystrophin at sarcolemma in a pig and the immunostaining for dystrophin on the formalin-fixed, paraffin-embedded (FFPE) tissue. The present case was found in a meat inspection center. The pig looked appeared healthy at the ante-mortem inspection. Muscular abnormalities were detected after carcass dressing as pale, discolored skeletal muscles with prominent fat infiltrations and considered so-called "fatty muscular dystrophy". Microscopic examination revealed following characteristics: diffused fat infiltration into the skeletal muscle and degeneration and regeneration of the remaining skeletal muscle fibers. Any lesions that were suspected of neurogenic atrophy, traumatic muscular degeneration, glycogen storage disease or other porcine muscular disorders were not observed. The immunostaining for dystrophin was conducted and confirmed to be applicable on FFPE porcine muscular tissues and revealed diminished stainability of dystrophin at the sarcolemma in the present case. Based on the histological observations and immunostaining results, the present case was diagnosed with BMD-like myopathy associated with dystrophin abnormality in a pig. Although the genetic properties were not clear, the present BMD-like myopathy implied the occurrence of dystrophinopathy in pigs. To the best of our knowledge, this is the first report of a natural case of myopathy associated with dystrophin abnormalities in a pig.

  8. Abnormal carbohydrate metabolism in a canine model for muscular dystrophy.

    PubMed

    Amaral, Andressa R; Brunetto, Márcio A; Brólio, Marina P; Cima, Daniela S; Miglino, Maria A; Santos, João Paulo F; Ambrósio, Carlos E

    2017-01-01

    The canine golden retriever muscular dystrophy (GRMD) model is the best animal model for studying Duchenne muscular dystrophy in humans. Considering the importance of glucose metabolism in the muscles, the existence of metabolic and endocrine alterations in a wide range of muscular dystrophies, and the pre-existing relationship between blood insulin concentration and muscular atrophy, the present study aimed to evaluate the postprandial glucose and insulin response in GRMD dogs. A total of eighteen golden retriever dogs were randomly distributed into three experimental groups: healthy/control (G1), female GRMD carriers (G2), and male dogs affected by GRMD (G3). Higher plasma resting glucose levels ( P = 0·0047) were seen in G2 and G3 compared with G1, as was the case for minimum ( P = <0·0001), mean ( P = 0·0002) and maximum ( P = 0·0359) glucose values for G3 compared with G1. Fructosamine concentrations were in accordance with reference values found in the literature for dogs. Insulin levels were lower in G3 compared with G1 ( P = 0·0065); however, there was no evidence of insulin resistance according to the homeostasis model assessment index values obtained. As for the evaluation of postprandial responses, fluctuations of glucose ( P = 0·0007) and insulin ( P = 0·0149) were observed in G1 and G2, while in G3 the values remained constant. The results allowed us to identify metabolic changes related to carbohydrate metabolism in GRMD dogs, highlighting the importance of adequate food management for these animals.

  9. Brillouin spectroscopy reveals changes in muscular viscoelasticity in Drosophila POMT mutants

    NASA Astrophysics Data System (ADS)

    Meng, Zhaokai; Baker, Ryan; Panin, Vladislav M.; Yakovlev, Vladislav V.

    2015-03-01

    Muscular dystrophy (MD) is a group of muscle diseases that induce weakness in skeletal muscle and cause progressive muscle degeneration. The muscular mechanical properties (i.e., viscoelasticity), however, have not been thoroughly examined before and after MD. On the other hand, Brillouin spectroscopy (BS) provides a non-invasive approach to probing the local sound speed within a small volume. Moreover, recent advances in background-free Brillouin spectroscopy enable investigators to imaging not only transparent samples, but also turbid ones. In this study, we investigated the mechanical properties of muscles while employing Drosophila model of dystroglycanopathies, human congenital muscular dystrophies resulting from abnormal glycosylation of alphadystroglycan. Specifically, we analyzed larval abdominal muscles of Drosophila with mutations in protein Omannosyltransferase (POMT) genes. As a comparison, we have also examined muscular tissues dissected from wildtype Drosophila. The Brillouin spectra were obtained by a background free VIPA (virtually imaged phased array) spectrometer described in the previous report. As a reference, the Raman spectra were also acquired for each test. Our current results indicated that POMT defects cause changes in muscle elasticity, which suggests that muscular dystrophy conditions may be also associated with abnormalities in muscle elastic properties.

  10. Anderson's disease (chylomicron retention disease): a new mutation in the SARA2 gene associated with muscular and cardiac abnormalities.

    PubMed

    Silvain, M; Bligny, D; Aparicio, T; Laforêt, P; Grodet, A; Peretti, N; Ménard, D; Djouadi, F; Jardel, C; Bégué, J M; Walker, F; Schmitz, J; Lachaux, A; Aggerbeck, L P; Samson-Bouma, M E

    2008-12-01

    Anderson's disease (AD) or chylomicron retention disease (CMRD) is a rare hereditary lipid malabsorption syndrome linked to SARA2 gene mutations. We report in this study a novel mutation in two sisters for which the Sar1b protein is predicted to be truncated by 32 amino acids at its carboxyl-terminus. Because the SARA2 gene is also expressed in the muscle, heart, liver and placenta, extraintestinal clinical manifestations may exist. For the first time, we describe in this study in the two sisters muscular as well as cardiac abnormalities that could be related to the reported expression of SARA2 in these tissues. We also evaluated six other patients for potential manifestations of the SARA2 mutation. The creatine phosphokinase levels were increased in all patients [1.5-9.4 x normal (N)] and transaminases were moderately elevated in five of the eight patients (1.2-2.6 x N), probably related to muscle disease rather than to liver dysfunction. A decreased ejection fraction occurred in one patient (40%, N: 60%). The muscle, liver and placental tissues that were examined had no specific abnormalities and, in particular, no lipid accumulation. These results suggest that myolysis and other extraintestinal abnormalities can occur in AD/CMRD and that the clinical evaluation of patients should reflect this.

  11. Autonomic dysfunction in muscular dystrophy: a theoretical framework for muscle reflex involvement

    PubMed Central

    Smith, Scott A.; Downey, Ryan M.; Williamson, Jon W.; Mizuno, Masaki

    2014-01-01

    Muscular dystrophies are a heterogeneous group of genetically inherited disorders whose most prominent clinical feature is progressive degeneration of skeletal muscle. In several forms of the disease, the function of cardiac muscle is likewise affected. The primary defect in this group of diseases is caused by mutations in myocyte proteins important to cellular structure and/or performance. That being stated, a growing body of evidence suggests that the development of autonomic dysfunction may secondarily contribute to the generation of skeletal and cardio-myopathy in muscular dystrophy. Indeed, abnormalities in the regulation of both sympathetic and parasympathetic nerve activity have been reported in a number of muscular dystrophy variants. However, the mechanisms mediating this autonomic dysfunction remain relatively unknown. An autonomic reflex originating in skeletal muscle, the exercise pressor reflex, is known to contribute significantly to the control of sympathetic and parasympathetic activity when stimulated. Given the skeletal myopathy that develops with muscular dystrophy, it is logical to suggest that the function of this reflex might also be abnormal with the pathogenesis of disease. As such, it may contribute to or exacerbate the autonomic dysfunction that manifests. This possibility along with a basic description of exercise pressor reflex function in health and disease are reviewed. A better understanding of the mechanisms that possibly underlie autonomic dysfunction in muscular dystrophy may not only facilitate further research but could also lead to the identification of new therapeutic targets for the treatment of muscular dystrophy. PMID:24600397

  12. The Effect of Aging on Muscular Dynamics Underlying Movement Patterns Changes.

    PubMed

    Vernooij, Carlijn A; Rao, Guillaume; Berton, Eric; Retornaz, Frédérique; Temprado, Jean-Jacques

    2016-01-01

    Introduction: Aging leads to alterations not only within the complex subsystems of the neuro-musculo-skeletal system, but also in the coupling between them. Here, we studied how aging affects functional reorganizations that occur both within and between the behavioral and muscular levels, which must be coordinated to produce goal-directed movements. Using unimanual reciprocal Fitts' task, we examined the behavioral and muscular dynamics of older adults (74.4 ± 3.7 years) and compared them to those found for younger adults (23.2 ± 2.0 years). Methods: To achieve this objective, we manipulated the target size to trigger a phase transition in the behavioral regime and searched for concomitant signatures of a phase transition in the muscular coordination. Here, muscular coordination was derived by using the method of muscular synergy extraction. With this technique, we obtained functional muscular patterns through non-negative matrix factorization of the muscular signals followed by clustering the resulting synergies. Results: Older adults showed a phase transition in behavioral regime, although, in contrast to young participants, their kinematic profiles did not show a discontinuity. In parallel, muscular coordination displayed two typical signatures of a phase transition, that is, increased variability of coordination patterns and a reorganization of muscular synergies. Both signatures confirmed the existence of muscular reorganization in older adults, which is coupled with change in dynamical regime at behavioral level. However, relative to young adults, transition occurred at lower index of difficulty (ID) in older participants and the reorganization of muscular patterns lasted longer (over multiple IDs). Discussion: This implies that consistent changes occur in coordination processes across behavior and muscle. Furthermore, the repertoire of muscular patterns was reduced and somewhat modified for older adults, relative to young participants. This suggests that

  13. RESPIRATORY DYSFUNCTION IN UNSEDATED DOGS WITH GOLDEN RETRIEVER MUSCULAR DYSTROPHY

    PubMed Central

    DeVanna, Justin C.; Kornegay, Joe N.; Bogan, Daniel J.; Bogan, Janet R.; Dow, Jennifer L.; Hawkins, Eleanor C.

    2013-01-01

    Golden retriever muscular dystrophy (GRMD) is a well-established model of Duchenne muscular dystrophy. The value of this model would be greatly enhanced with practical tools to monitor progression of respiratory dysfunction during treatment trials. Arterial blood gas analysis, tidal breathing spirometry, and respiratory inductance plethysmography (RIP) were performed to determine if quantifiable abnormalities could be identified in unsedated, untrained, GRMD dogs. Results from 11 dogs with a mild phenotype of GRMD and 11 age-matched carriers were compared. Arterial blood gas analysis was successfully performed in all dogs, spirometry in 21 of 22 (95%) dogs, and RIP in 18 of 20 (90%) dogs. Partial pressure of carbon dioxide and bicarbonate concentration were higher in GRMD dogs. Tidal breathing peak expiratory flows were markedly higher in GRMD dogs. Abnormal abdominal motion was present in 7 of 10 (70%) GRMD dogs. Each technique provided objective, quantifiable measures that will be useful for monitoring respiratory function in GRMD dogs during clinical trials while avoiding the influence of sedation on results. Increased expiratory flows and the pattern of abdominal breathing are novel findings, not reported in people with Duchenne muscular dystrophy, and might be a consequence of hyperinflation. PMID:24295812

  14. Respiratory function in facioscapulohumeral muscular dystrophy 1.

    PubMed

    Wohlgemuth, M; Horlings, C G C; van der Kooi, E L; Gilhuis, H J; Hendriks, J C M; van der Maarel, S M; van Engelen, B G M; Heijdra, Y F; Padberg, G W

    2017-06-01

    To test the hypothesis that wheelchair dependency and (kypho-)scoliosis are risk factors for developing respiratory insufficiency in facioscapulohumeral muscular dystrophy, we examined 81 patients with facioscapulohumeral muscular dystrophy 1 of varying degrees of severity ranging from ambulatory patients to wheelchair-bound patients. We examined the patients neurologically and by conducting pulmonary function tests: Forced Vital Capacity, Forced Expiratory Volume in 1 second, and static maximal inspiratory and expiratory mouth pressures. We did not find pulmonary function test abnormalities in ambulant facioscapulohumeral muscular dystrophy patients. Even though none of the patients complained of respiratory dysfunction, mild to severe respiratory insufficiency was found in more than one third of the wheelchair-dependent patients. Maximal inspiratory pressures and maximal expiratory pressures were decreased in most patients, with a trend that maximal expiratory pressures were more affected than maximal inspiratory pressures. Wheelchair-dependent patients with (kypho-)scoliosis showed the most restricted lung function. Wheelchair-dependent patients with (kypho-)scoliosis are at risk for developing respiratory function impairment. We advise examining this group of facioscapulohumeral muscular dystrophy patients periodically, even in the absence of symptoms of respiratory insufficiency, given its frequency and impact on daily life and the therapeutic consequences. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Abnormalities in early markers of muscle involvement support a delay in myogenesis in spinal muscular atrophy.

    PubMed

    Martínez-Hernández, Rebeca; Bernal, Sara; Alias, Laura; Tizzano, Eduardo F

    2014-06-01

    Spinal muscular atrophy (SMA) is characterized by loss of motor neurons in the spinal cord that results in muscle denervation and profound weakness in affected patients. We sought evidence for primary muscle involvement in the disease during human development by analyzing the expression of several muscle cytoskeletal components (i.e. slow, fast, and developmental myosin, desmin, and vimentin) in fetal or postnatal skeletal muscle samples from 5 SMA cases and 6 controls. At 14 weeks' gestation, SMA samples had higher percentages of myotubes expressing fast myosin and lower percentages of myotubes expressing slow myosin versus control samples. Desmin and vimentin were highly expressed at prenatal stages without notable differences between control and SMA samples, although both proteins showed persistent immunostaining in atrophic fibers in postnatal SMA samples. We also studied the expression of Pax7-positive nuclei as a marker of satellite cells and found no differences between control and SMA prenatal samples. There was, however, a significant increase in satellite cells in postnatal atrophic SMA fibers, suggesting an abnormal myogenic process. Together, these results support the hypothesis of a delay in muscle maturation as one of the primary pathologic components of SMA. Furthermore, myosins and Pax7 may be useful research markers of muscle involvement in this disease.

  16. Impaired coupling of local and global functional feedbacks underlies abnormal synchronization and negative symptoms of schizophrenia.

    PubMed

    Noh, Kyungchul; Shin, Kyung Soon; Shin, Dongkwan; Hwang, Jae Yeon; Kim, June Sic; Jang, Joon Hwan; Chung, Chun Kee; Kwon, Jun Soo; Cho, Kwang-Hyun

    2013-04-10

    Abnormal synchronization of brain oscillations is found to be associated with various core symptoms of schizophrenia. However, the underlying mechanism of this association remains yet to be elucidated. In this study, we found that coupled local and global feedback (CLGF) circuits in the cortical functional network are related to the abnormal synchronization and also correlated to the negative symptom of schizophrenia. Analysis of the magnetoencephalography data obtained from patients with chronic schizophrenia during rest revealed an increase in beta band synchronization and a reduction in gamma band power compared to healthy controls. Using a feedback identification method based on non-causal impulse responses, we constructed functional feedback networks and found that CLGF circuits were significantly reduced in schizophrenia. From computational analysis on the basis of the Wilson-Cowan model, we unraveled that the CLGF circuits are critically involved in the abnormal synchronization and the dynamical switching between beta and gamma bands power in schizophrenia. Moreover, we found that the abundance of CLGF circuits was negatively correlated with the development of negative symptoms of schizophrenia, suggesting that the negative symptom is closely related to the impairment of this circuit. Our study implicates that patients with schizophrenia might have the impaired coupling of inter- and intra-regional functional feedbacks and that the CLGF circuit might serve as a critical bridge between abnormal synchronization and the negative symptoms of schizophrenia.

  17. Evaluation of muscular lesions in connective tissue diseases: thallium 201 muscular scans

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Guillet, G.; Guillet, J.; Sanciaume, C.

    1988-04-01

    We performed thallium 201 muscle scans to assess muscular involvement in 40 patients with different connective tissue diseases (7 with dermatomyositis, 7 with systemic lupus erythematosus, 12 with progressive systemic scleroderma, 2 with calcinosis, Raynaud's phenomenon, esophageal involvement, sclerodactyly, and telangiectasia (CREST) syndrome, 3 with monomelic scleroderma, 6 with morphea, and 3 with Raynaud's disease). Only 12 of these patients complained of fatigability and/or myalgia. Electromyography was performed and serum levels of muscle enzymes were measured in all patients. Comparison of thallium 201 exercise recording with the other tests revealed that scan sensitivity is greater than electromyographic and serum musclemore » enzymes levels. Thallium 201 scans showed abnormal findings in 32 patients and revealed subclinical lesions in 18 patients, while electromyography findings were abnormal in 25 of these 32 patients. Serum enzyme levels were raised in only 8 patients. Thallium 201 scanning proved to be a useful guide for modifying therapy when laboratory data were conflicting. It was useful to evaluate treatment efficacy. Because our data indicate a 100% positive predictive value, we believe that thallium 201 scanning should be advised for severe systemic connective tissue diseases with discordant test results.« less

  18. Muscular dystrophy - resources

    MedlinePlus

    Resources - muscular dystrophy ... The following organizations are good resources for information on muscular dystrophy : Muscular Dystrophy Association -- www.mda.org National Institute of Neurological Disorders and Stroke -- www.ninds.nih. ...

  19. Weakly coupled map lattice models for multicellular patterning and collective normalization of abnormal single-cell states

    NASA Astrophysics Data System (ADS)

    García-Morales, Vladimir; Manzanares, José A.; Mafe, Salvador

    2017-04-01

    We present a weakly coupled map lattice model for patterning that explores the effects exerted by weakening the local dynamic rules on model biological and artificial networks composed of two-state building blocks (cells). To this end, we use two cellular automata models based on (i) a smooth majority rule (model I) and (ii) a set of rules similar to those of Conway's Game of Life (model II). The normal and abnormal cell states evolve according to local rules that are modulated by a parameter κ . This parameter quantifies the effective weakening of the prescribed rules due to the limited coupling of each cell to its neighborhood and can be experimentally controlled by appropriate external agents. The emergent spatiotemporal maps of single-cell states should be of significance for positional information processes as well as for intercellular communication in tumorigenesis, where the collective normalization of abnormal single-cell states by a predominantly normal neighborhood may be crucial.

  20. Weakly coupled map lattice models for multicellular patterning and collective normalization of abnormal single-cell states.

    PubMed

    García-Morales, Vladimir; Manzanares, José A; Mafe, Salvador

    2017-04-01

    We present a weakly coupled map lattice model for patterning that explores the effects exerted by weakening the local dynamic rules on model biological and artificial networks composed of two-state building blocks (cells). To this end, we use two cellular automata models based on (i) a smooth majority rule (model I) and (ii) a set of rules similar to those of Conway's Game of Life (model II). The normal and abnormal cell states evolve according to local rules that are modulated by a parameter κ. This parameter quantifies the effective weakening of the prescribed rules due to the limited coupling of each cell to its neighborhood and can be experimentally controlled by appropriate external agents. The emergent spatiotemporal maps of single-cell states should be of significance for positional information processes as well as for intercellular communication in tumorigenesis, where the collective normalization of abnormal single-cell states by a predominantly normal neighborhood may be crucial.

  1. Functional capacity and muscular abnormalities in subclinical hypothyroidism.

    PubMed

    Reuters, Vaneska S; Teixeira, Patrícia de Fátima S; Vigário, Patrícia S; Almeida, Cloyra P; Buescu, Alexandre; Ferreira, Márcia M; de Castro, Carmen L N; Gold, Jaime; Vaisman, Mario

    2009-10-01

    Neuromuscular abnormalities and low exercise tolerance are frequently observed in overt hypothyroidism, but it remains controversial if they can also occur in subclinical hypothyroidism (sHT). The aim of this study is to evaluate neuromuscular symptoms, muscle strength, and exercise capacity in sHT, compared with healthy euthyroid individuals. A cross-sectional study was performed with 44 sHT and 24 euthyroid outpatients from a university hospital. Neuromuscular symptoms were questioned. Muscle strength was tested for neck, shoulder, arm, and hip muscle groups, using manual muscle testing (MMT). Quadriceps muscle strength was tested with a chair dynamometer and inspiratory muscle strength (IS) by a manuvacuometer. Functional capacity was estimated based on the peak of oxygen uptake (mL/kg/min), using the Bruce treadmill protocol. Cramps (54.8% versus 25.0%; P < 0.05), weakness (45.2% versus 12.6; P < 0.05), myalgia (47.6% versus 25.0%; P = 0.07), and altered MMT (30.8% versus 8.3%; P = 0.040) were more frequent in sHT. Quadriceps strength and IS were not impaired in sHT and the same was observed for functional capacity. IS was significantly lower in patients complaining of fatigue and weakness (P < 0.05) and tended to be lower in those with altered MMT (P = 0.090). Neuromuscular complaints and altered MMT were significantly more frequent in sHT than in controls, and IS was lower in patients with these abnormalities. Results suggest that altered muscle strength by MMT and the coexistence of neuromuscular complaints in patients with sHT may indicate neuromuscular dysfunction.

  2. Consensus statement for standard of care in spinal muscular atrophy.

    PubMed

    Wang, Ching H; Finkel, Richard S; Bertini, Enrico S; Schroth, Mary; Simonds, Anita; Wong, Brenda; Aloysius, Annie; Morrison, Leslie; Main, Marion; Crawford, Thomas O; Trela, Anthony

    2007-08-01

    Spinal muscular atrophy is a neurodegenerative disease that requires multidisciplinary medical care. Recent progress in the understanding of molecular pathogenesis of spinal muscular atrophy and advances in medical technology have not been matched by similar developments in the care for spinal muscular atrophy patients. Variations in medical practice coupled with differences in family resources and values have resulted in variable clinical outcomes that are likely to compromise valid measure of treatment effects during clinical trials. The International Standard of Care Committee for Spinal Muscular Atrophy was formed in 2005, with a goal of establishing practice guidelines for clinical care of these patients. The 12 core committee members worked with more than 60 spinal muscular atrophy experts in the field through conference calls, e-mail communications, a Delphi survey, and 2 in-person meetings to achieve consensus on 5 care areas: diagnostic/new interventions, pulmonary, gastrointestinal/nutrition, orthopedics/rehabilitation, and palliative care. Consensus was achieved on several topics related to common medical problems in spinal muscular atrophy, diagnostic strategies, recommendations for assessment and monitoring, and therapeutic interventions in each care area. A consensus statement was drafted to address the 5 care areas according to 3 functional levels of the patients: nonsitter, sitter, and walker. The committee also identified several medical practices lacking consensus and warranting further investigation. It is the authors' intention that this document be used as a guideline, not as a practice standard for their care. A practice standard for spinal muscular atrophy is urgently needed to help with the multidisciplinary care of these patients.

  3. Chromosomal abnormalities as a cause of recurrent abortions in Egypt

    PubMed Central

    El-Dahtory, Faeza Abdel Mogib

    2011-01-01

    BACKGROUND: In 4%-8% of couples with recurrent abortion, at least one of the partners has chromosomal abnormality. Most spontaneous miscarriages which happen in the first and second trimesters are caused by chromosomal abnormalities. These chromosomal abnormalities may be either numerical or structural. MATERIAL AND METHODS: Cytogenetic study was done for 73 Egyptian couples who presented with recurrent abortion at Genetic Unit of Children Hospital, Mansoura University. RESULTS: We found that the frequency of chromosomal abnormalities was not significantly different from that reported worldwide. Chromosomal abnormalities were detected in 9 (6.1%) of 73 couples. Seven of chromosomal abnormalities were structural and two of them were numerical. CONCLUSION: Our results showed that 6.1% of the couples with recurrent abortion had chromosomal abnormalities, with no other abnormalities. We suggest that it is necessary to perform cytogenetic in vestigation for couples who have recurrent abortion. PMID:22090718

  4. [Central Nervous Involvement in Patients with Fukuyama Congenital Muscular Dystrophy].

    PubMed

    Ishigaki, Keiko

    2016-02-01

    Fukuyama congenital muscular dystrophy (FCMD), the second most common muscular dystrophy in the Japanese population, is an autosomal recessive disorder caused by mutations in the fukutin (FKTN) gene. The main features of FCMD are a combination of infantile-onset hypotonia, generalized muscle weakness, eye abnormalities and central nervous system involvement with mental retardation and seizures associated with cortical migration defects. The FKTN gene product is thought to be necessary for maintaining migrating neurons in an immature state during migration, and for supporting migration via α-dystroglycan in the central nervous system. Typical magnetic resonance imaging findings in FCMD patients are cobblestone lissencephaly and cerebellar cystic lesions. White matter abnormalities with hyperintensity on T(2)-weighted images are seen especially in younger patients and those with severe phenotypes. Most FCMD patients are mentally retarded and the level is moderate to severe, with IQs ranging from 30 to 50. In our recent study, 62% of patients developed seizures. Among them, 71% had only febrile seizures, 6% had afebrile seizures from the onset, and 22% developed afebrile seizures following febrile seizures. Most patients had seizures that were controllable with just 1 type of antiepileptic drug, but 18% had intractable seizures that must be treated with 3 medications.

  5. [Specific features of Becker Muscular Dystrophy patients and female carriers of Duchenne Muscular Dystrophy].

    PubMed

    Magot, A; Mercier, S; Péréon, Y

    2015-12-01

    Becker muscular dystrophy (BMD) was first described in 1955 and linked to the DMD gene in 1987. Compared to Duchenne muscular dystrophy (DMD), clinical onset of BMD usually occurs after the age of 12 and wheelchair is required after the age of 16. BMD is characterized by generalized weakness first affecting limb girdle muscles, hypertrophy of the calves and cardiomyopathy in males. Some patients have only mild symptoms such as cramps or elevated serum creatine kinases (SCK) throughout all their lives. SCK levels are usually elevated. Muscle biopsy (immunohistochemistry or immunoblotting) shows a dystrophic pattern with abnormal dystrophin staining. Diagnosis is confirmed by DMD gene sequencing. Deletions or duplications of one or several exons are identified in the majority of cases. A multidisciplinary approach is recommended for the care management of these patients with a particular attention to the cardiomyopathy, which is typically responsible for death but can be prevented by specific treatment. X-linked dilated cardiomyopathies linked to DMD gene are a phenotypic continuum of BMD. Some female carriers of DMD mutations exhibit clinical symptoms of variable severity, often milder and beginning later than in males. The cardiomyopathy is the most frequent feature that should be especially monitored in these patients. Genetic counselling should be systematically proposed. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  6. Muscular Dystrophy with Ribitol-Phosphate Deficiency: A Novel Post-Translational Mechanism in Dystroglycanopathy

    PubMed Central

    Kanagawa, Motoi; Toda, Tatsushi

    2017-01-01

    Muscular dystrophy is a group of genetic disorders characterized by progressive muscle weakness. In the early 2000s, a new classification of muscular dystrophy, dystroglycanopathy, was established. Dystroglycanopathy often associates with abnormalities in the central nervous system. Currently, at least eighteen genes have been identified that are responsible for dystroglycanopathy, and despite its genetic heterogeneity, its common biochemical feature is abnormal glycosylation of alpha-dystroglycan. Abnormal glycosylation of alpha-dystroglycan reduces its binding activities to ligand proteins, including laminins. In just the last few years, remarkable progress has been made in determining the sugar chain structures and gene functions associated with dystroglycanopathy. The normal sugar chain contains tandem structures of ribitol-phosphate, a pentose alcohol that was previously unknown in humans. The dystroglycanopathy genes fukutin, fukutin-related protein (FKRP), and isoprenoid synthase domain-containing protein (ISPD) encode essential enzymes for the synthesis of this structure: fukutin and FKRP transfer ribitol-phosphate onto sugar chains of alpha-dystroglycan, and ISPD synthesizes CDP-ribitol, a donor substrate for fukutin and FKRP. These findings resolved long-standing questions and established a disease subgroup that is ribitol-phosphate deficient, which describes a large population of dystroglycanopathy patients. Here, we review the history of dystroglycanopathy, the properties of the sugar chain structure of alpha-dystroglycan, dystroglycanopathy gene functions, and therapeutic strategies. PMID:29081423

  7. Cardiac involvement in facio-scapulo-humeral muscular dystrophy: a family study using Thallium-201 single-photon-emission-computed tomography.

    PubMed

    Faustmann, P M; Farahati, J; Rupilius, B; Dux, R; Koch, M C; Reiners, C

    1996-12-01

    Fifteen persons from two consecutive generations of one family affected with facio-scapulo-humeral muscular dystrophy (FSHD) were clinically and neurophysiologically examined. Diagnostic muscle biopsies were obtained from two members. Linkage analysis showed that all four affected members of the family inherit the same 4q35 haplotype giving a lod score of z = +1.44. Six family members were examined by ECG at rest and under stress, by two-dimensional echocardiography, and by cardiac Thallium-201 single-photon-emission computed tomography (Tl-201-SPECT) under dobutamine stress and at rest. Abnormal reduced Tl-201 uptake in cardiac SPECT was only found in the affected members of the family. Therefore we suggest that cardiac Tl-201-SPECT abnormalities in FSHD reflect cardiomyogenic changes in this type of muscular disease.

  8. Myoglobin in Primary Muscular Disease: I. Duchenne Muscular Dystrophy: and: II. Muscular Dystrophy of Distal Type

    PubMed Central

    Romero-Herrera, A. E.; Lehmann, H.; Tomlinson, B. E.; Walton, J. N.

    1973-01-01

    Skeletal myoglobin from two cases of muscular dystrophy, one of Duchenne muscular dystrophy, and one of muscular dystrophy of distal type, have been examined and no differences from normal human myoglobin were found. The opportunity has been taken to discuss the nature of minor fractions of myoglobin-like material which are found when human skeletal myoglobin is isolated. Those which have been observed in the present study have been artefacts and it was possible to demonstrate that they were due to deamidation of certain glutamine and asparagine residues. Images PMID:4590363

  9. Late onset GM2 gangliosidosis mimicking spinal muscular atrophy.

    PubMed

    Jamrozik, Z; Lugowska, A; Gołębiowski, M; Królicki, L; Mączewska, J; Kuźma-Kozakiewicz, M

    2013-09-25

    A case of late onset GM2 gangliosidodis with spinal muscular atrophy phenotype followed by cerebellar and extrapyramidal symptoms is presented. Genetic analysis revealed compound heterozygous mutation in exon 10 of the HEXA gene. Patient has normal intelligence and emotional reactivity. Neuroimaging tests of the brain showed only cerebellar atrophy consistent with MR spectroscopy (MRS) abnormalities. (18)F-fluorodeoxyglucose positron emission tomography (18)F-FDG PET/CT of the brain revealed glucose hypometabolism in cerebellum and in temporal and occipital lobes bilaterally. © 2013 Elsevier B.V. All rights reserved.

  10. Merosin-deficient congenital muscular dystrophy with mental retardation and cerebellar cysts, unlinked to the LAMA2, FCMD, MEB and CMD1B loci, in three Tunisian patients.

    PubMed

    Triki, Chahnez; Louhichi, Nacim; Méziou, Mériam; Choyakh, Fakher; Kéchaou, Mohamed Salah; Jlidi, Rachid; Mhiri, Chokri; Fakhfakh, Faiza; Ayadi, Hamadi

    2003-01-01

    We report three Tunisian patients affected by congenital muscular dystrophy with mental retardation and cerebellar cysts on cranial magnetic resonance imaging. The clinical features were characterized by hypotonia at birth, joint contractures associated with severe psychomotor retardation, absence of speech, inability to walk in three patients, but calf hypertrophy was noted only in two patients. Brain magnetic resonance imaging showed several cerebellar cysts and vermis hypoplasia in all of the patients. Abnormality of the white matter was present in two patients. The pattern of gyration was normal in all cases. Serum creatine kinase was elevated in all three cases and their muscle biopsy showed dystrophic changes compatible with congenital muscular dystrophy. The immunohistochemical analysis of the skeletal muscle revealed partial merosin deficiency, more pronounced for the N-terminal antibody. Linkage analysis excluded congenital muscular dystrophy loci on chromosomes 6q22, 9q31, 1p32 and 1q42. These patients constituted a particular form of congenital muscular dystrophy with a combination of severe motor delay, mental retardation, partial merosin deficiency and cerebellar cysts. Two patients showed white matter abnormalities on magnetic resonance imaging and hypertrophy of the calves. These cases, in addition to those reported previously, confirmed the large phenotypic variability in the group of secondary merosin deficiency congenital muscular dystrophy.

  11. Occurrence of Emery-Dreifuss muscular dystrophy in a rural setting of Cameroon: a case report and review of the literature.

    PubMed

    Ekabe, Cyril Jabea; Kehbila, Jules; Sama, Carlson-Babila; Kadia, Benjamin Momo; Abanda, Martin Hongieh; Monekosso, Gottlieb Lobe

    2017-01-09

    Emery-Dreifuss muscular dystrophy is a rare genetic muscular disease, presenting mainly with contractures, weakness and cardiac conduction abnormalities. Its clinical and laboratory similarities to other muscular dystrophies, and rarity poses diagnostic challenges, requiring a high index of suspicion in resource limited settings. An 8 year old sub-Saharan male presented with rigidity and deformity of both elbows and ankles, and weakness of the upper limbs and lower limbs for duration of 4 months. This progressed to inability to stand and walk. There was no mental impairment. Physical examination was remarkable for contractures of the elbows and ankles, and wasting of muscles of the limbs and trunk, with a scapulohumeroperoneal pattern, and tachycardia. After laboratory investigations, a diagnosis of Emery-Dreifuss muscular dystrophy was suspected. Physiotherapy was started, wheel chair was prescribed, and referral to a specialist center was done for appropriate management. Emery-Dreifuss muscular dystrophy is a rare disabling muscular disease which poses a diagnostic challenge. High index of suspicion is paramount for its early diagnoses to prevent orthopedic and cardiac complications. Prompt diagnosis and management is essential to improve on the prognosis of this disease.

  12. Abnormal Collagen Metabolism in Cultured Skin Fibroblasts from Patients with Duchenne Muscular Dystrophy

    NASA Astrophysics Data System (ADS)

    Rodemann, H. Peter; Bayreuther, Klaus

    1984-08-01

    Total collagen synthesis is decreased by about 29% (P < 0.01) in skin fibroblasts established in vitro from male patients with Duchenne muscular dystrophy (DMD) as compared with that in normal male skin fibroblasts in vitro. The reduction in collagen synthesis is associated with an approximately 2-fold increase in collagen degradation in DMD fibroblasts. Correlated to these alterations in the metabolism of collagen, DMD fibroblasts express a significantly higher hydroxyproline/proline ratio (DMD: 1.36-1.45; P < 0.01) than do normal fibroblasts (controls: 0.86-0.89). The increased hydroxylation of proline residues of collagen (composed of type I and type III) could be the cause for the enhanced degradation of collagen in DMD fibroblasts.

  13. Evaluation of Limb-Girdle Muscular Dystrophy

    ClinicalTrials.gov

    2014-03-06

    Becker Muscular Dystrophy; Limb-Girdle Muscular Dystrophy, Type 2A (Calpain-3 Deficiency); Limb-Girdle Muscular Dystrophy, Type 2B (Miyoshi Myopathy, Dysferlin Deficiency); Limb-Girdle Muscular Dystrophy, Type 2I (FKRP-deficiency)

  14. Muscular dystrophies due to defective glycosylation of dystroglycan

    PubMed Central

    Muntoni, F; Brockington, M; Godfrey, C; Ackroyd, M; Robb, S.; Manzur, A; Kinali, M; Mercuri, E; Kaluarachchi, M; Feng, L; Jimenez-Mallebrera, C.; Clement, E; Torelli, S; Sewry, CA; Brown, SC

    2007-01-01

    Summary Muscular dystrophies are a clinically and genetically heterogeneous group of disorders. Until recently most of the proteins associated with muscular dystrophies were believed to be proteins of the sarcolemma associated with reinforcing the plasma membrane or in facilitating its re-sealing following injury. In the last few years a novel and frequent pathogenic mechanism has been identified that involves the abnormal glycosylation of alpha-dystroglycan (ADG). This peripheral membrane protein undergoes complex and crucial glycosylation steps that enable it to interact with LG domain containing extracellular matrix proteins such as laminins, agrin and perlecan. Mutations in six genes (POMT1, POMT2, POMGnT1, fukutin, FKRP and LARGE) have been identified in patients with reduced glycosylation of ADG. While initially a clear correlation between gene defect and phenotype was observed for each of these 6 genes (for example, Walker Warburg syndrome was associated with mutations in POMT1 and POMT2, Fukuyama congenital muscular dystrophy associated with fukutin mutations, and Muscle Eye Brain disease associated with POMGnT1 mutations), we have recently demonstrated that allelic mutations in each of these 6 genes can result in a much wider spectrum of clinical conditions. Thus, the crucial aspect in determining the phenotypic severity is not which gene is primarily mutated, but how severely the mutation affects the glycosylation of ADG. Systematic mutation analysis of these 6 glycosyltransferases in patients with a dystroglycan glycosylation disorder identifies mutations in approximately 65% suggesting that more genes have yet to be identified. PMID:18646561

  15. Translating golden retriever muscular dystrophy microarray findings to novel biomarkers for cardiac/skeletal muscle function in Duchenne muscular dystrophy.

    PubMed

    Galindo, Cristi L; Soslow, Jonathan H; Brinkmeyer-Langford, Candice L; Gupte, Manisha; Smith, Holly M; Sengsayadeth, Seng; Sawyer, Douglas B; Benson, D Woodrow; Kornegay, Joe N; Markham, Larry W

    2016-04-01

    In Duchenne muscular dystrophy (DMD), abnormal cardiac function is typically preceded by a decade of skeletal muscle disease. Molecular reasons for differences in onset and progression of these muscle groups are unknown. Human biomarkers are lacking. We analyzed cardiac and skeletal muscle microarrays from normal and golden retriever muscular dystrophy (GRMD) dogs (ages 6, 12, or 47+ mo) to gain insight into muscle dysfunction and to identify putative DMD biomarkers. These biomarkers were then measured using human DMD blood samples. We identified GRMD candidate genes that might contribute to the disparity between cardiac and skeletal muscle disease, focusing on brain-derived neurotropic factor (BDNF) and osteopontin (OPN/SPP1, hereafter indicated as SPP1). BDNF was elevated in cardiac muscle of younger GRMD but was unaltered in skeletal muscle, while SPP1 was increased only in GRMD skeletal muscle. In human DMD, circulating levels of BDNF were inversely correlated with ventricular function and fibrosis, while SPP1 levels correlated with skeletal muscle function. These results highlight gene expression patterns that could account for differences in cardiac and skeletal disease in GRMD. Most notably, animal model-derived data were translated to DMD and support use of BDNF and SPP1 as biomarkers for cardiac and skeletal muscle involvement, respectively.

  16. Cesarean section scar as a cause of abnormal vaginal bleeding: diagnosis by sonohysterography.

    PubMed

    Thurmond, A S; Harvey, W J; Smith, S A

    1999-01-01

    A previously undescribed cause of abnormal uterine bleeding is presented. Nine of 310 women evaluated by sonohysterography for abnormal bleeding demonstrated an 8 to 17 mm gap in the anterior lower uterine segment myometrium at the site of prior cesarean deliveries. All women were premenopausal and had a history of 2 to 12 days of postmenstrual spotting. Presumably a lack of coordinated muscular contractions occurs around the cesarean scar, allowing the defect to collect menstrual debris. Subsequently, the debris leaches out through the cervix for several days after the majority of menstrual flow has ceased.

  17. Endoplasmic reticulum stress in spinal and bulbar muscular atrophy: a potential target for therapy

    PubMed Central

    Montague, Karli; Malik, Bilal; Gray, Anna L.; La Spada, Albert R.; Hanna, Michael G.; Szabadkai, Gyorgy

    2014-01-01

    Spinal and bulbar muscular atrophy is an X-linked degenerative motor neuron disease caused by an abnormal expansion in the polyglutamine encoding CAG repeat of the androgen receptor gene. There is evidence implicating endoplasmic reticulum stress in the development and progression of neurodegenerative disease, including polyglutamine disorders such as Huntington’s disease and in motor neuron disease, where cellular stress disrupts functioning of the endoplasmic reticulum, leading to induction of the unfolded protein response. We examined whether endoplasmic reticulum stress is also involved in the pathogenesis of spinal and bulbar muscular atrophy. Spinal and bulbar muscular atrophy mice that carry 100 pathogenic polyglutamine repeats in the androgen receptor, and develop a late-onset neuromuscular phenotype with motor neuron degeneration, were studied. We observed a disturbance in endoplasmic reticulum-associated calcium homeostasis in cultured embryonic motor neurons from spinal and bulbar muscular atrophy mice, which was accompanied by increased endoplasmic reticulum stress. Furthermore, pharmacological inhibition of endoplasmic reticulum stress reduced the endoplasmic reticulum-associated cell death pathway. Examination of spinal cord motor neurons of pathogenic mice at different disease stages revealed elevated expression of markers for endoplasmic reticulum stress, confirming an increase in this stress response in vivo. Importantly, the most significant increase was detected presymptomatically, suggesting that endoplasmic reticulum stress may play an early and possibly causal role in disease pathogenesis. Our results therefore indicate that the endoplasmic reticulum stress pathway could potentially be a therapeutic target for spinal and bulbar muscular atrophy and related polyglutamine diseases. PMID:24898351

  18. Muscular dystrophy in a dog resembling human becker muscular dystrophy.

    PubMed

    Baroncelli, A B; Abellonio, F; Pagano, T B; Esposito, I; Peirone, B; Papparella, S; Paciello, O

    2014-05-01

    A 3-year-old, male Labrador retriever dog was presented with clinical signs of progressive exercise intolerance, bilateral elbow extension, rigidity of the forelimbs, hindlimb flexion and kyphosis. Microscopical examination of muscle tissue showed marked variability in myofibre size, replacement of muscle with mature adipose tissue and degeneration/regeneration of muscle fibres, consistent with muscular dystrophy. Immunohistochemical examination for dystrophin showed markedly reduced labelling with monoclonal antibodies specific for the rod domain and the carboxy-terminal of dystrophin, while expression of β-sarcoglycan, γ-sarcoglycan and β-dystroglycan was normal. Immunoblotting revealed a truncated dystrophin protein of approximately 135 kDa. These findings supported a diagnosis of congenital canine muscular dystrophy resembling Becker muscular dystrophy in man. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Characterization of dystrophin deficient rats: a new model for Duchenne muscular dystrophy.

    PubMed

    Larcher, Thibaut; Lafoux, Aude; Tesson, Laurent; Remy, Séverine; Thepenier, Virginie; François, Virginie; Le Guiner, Caroline; Goubin, Helicia; Dutilleul, Maéva; Guigand, Lydie; Toumaniantz, Gilles; De Cian, Anne; Boix, Charlotte; Renaud, Jean-Baptiste; Cherel, Yan; Giovannangeli, Carine; Concordet, Jean-Paul; Anegon, Ignacio; Huchet, Corinne

    2014-01-01

    A few animal models of Duchenne muscular dystrophy (DMD) are available, large ones such as pigs or dogs being expensive and difficult to handle. Mdx (X-linked muscular dystrophy) mice only partially mimic the human disease, with limited chronic muscular lesions and muscle weakness. Their small size also imposes limitations on analyses. A rat model could represent a useful alternative since rats are small animals but 10 times bigger than mice and could better reflect the lesions and functional abnormalities observed in DMD patients. Two lines of Dmd mutated-rats (Dmdmdx) were generated using TALENs targeting exon 23. Muscles of animals of both lines showed undetectable levels of dystrophin by western blot and less than 5% of dystrophin positive fibers by immunohistochemistry. At 3 months, limb and diaphragm muscles from Dmdmdx rats displayed severe necrosis and regeneration. At 7 months, these muscles also showed severe fibrosis and some adipose tissue infiltration. Dmdmdx rats showed significant reduction in muscle strength and a decrease in spontaneous motor activity. Furthermore, heart morphology was indicative of dilated cardiomyopathy associated histologically with necrotic and fibrotic changes. Echocardiography showed significant concentric remodeling and alteration of diastolic function. In conclusion, Dmdmdx rats represent a new faithful small animal model of DMD.

  20. Rhabdomyolysis featuring muscular dystrophies.

    PubMed

    Lahoria, Rajat; Milone, Margherita

    2016-02-15

    Rhabdomyolysis is a potentially life threatening condition of various etiology. The association between rhabdomyolysis and muscular dystrophies is under-recognized in clinical practice. To identify muscular dystrophies presenting with rhabdomyolysis at onset or as predominant feature. We retrospectively reviewed clinical and laboratory data of patients with a genetically confirmed muscular dystrophy in whom rhabdomyolysis was the presenting or main clinical manifestation. Thirteen unrelated patients (males=6; females=7) were identified. Median age at time of rhabdomyolysis was 18 years (range, 2-47) and median duration between the first episode of rhabdomyolysis and molecular diagnosis was 2 years. Fukutin-related protein (FKRP) muscular dystrophy (n=6) was the most common diagnosis, followed by anoctaminopathy-5 (n=3), calpainopathy-3 (n=2) and dystrophinopathy (n=2). Four patients experienced recurrent rhabdomyolysis. Eight patients were asymptomatic and 3 reported myalgia and exercise intolerance prior to the rhabdomyolysis. Exercise (n=6) and fever (n=4) were common triggers; rhabdomyolysis was unprovoked in 3 patients. Twelve patients required hospitalization. Baseline CK levels were elevated in all patients (median 1200 IU/L; range, 600-3600). Muscular dystrophies can present with rhabdomyolysis; FKRP mutations are particularly frequent in causing such complication. A persistently elevated CK level in patients with rhabdomyolysis warrants consideration for underlying muscular dystrophy. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Central Arterial Function Measured by Non-invasive Pulse Wave Analysis is Abnormal in Patients with Duchenne Muscular Dystrophy.

    PubMed

    Ryan, Thomas D; Parent, John J; Gao, Zhiqian; Khoury, Philip R; Dupont, Elizabeth; Smith, Jennifer N; Wong, Brenda; Urbina, Elaine M; Jefferies, John L

    2017-08-01

    Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder caused by mutation of dystrophin. Cardiovascular involvement includes dilated cardiomyopathy. Non-invasive assessment of vascular function has not been evaluated in DMD. We hypothesize arterial wave reflection is abnormal in patients with DMD. Pulse wave analysis was performed on DMD patients with a SphygmoCor SCOR-PVx System to determine central blood pressure and augmentation index (AIx) as an assessment of arterial wave reflection. Results were compared to a control group. A total of 43 patients with DMD were enrolled, and compared to 43 normal controls. Central systolic blood pressure was lower, while both AIx-75 (7.8 ± 9.6% vs. 2.1 ± 10.4%, p 0.01, DMD vs. normal) and AIx-not corrected (16.8 ± 10.1% vs. -3.6 ± 10.9, p < 0.001, DMD vs. normal) were higher in the DMD compared to control. Using multivariable linear regression model, the variables found to have a significant effect on AIx-not corrected included diagnosis of DMD, height, and heart rate (r 2  = 0.257). The current data suggest that, despite lower central systolic blood pressure, patients with DMD have higher wave reflection when compared to normal controls, which may represent increased arterial stiffness. Overall there appears to be no effect on ventricular systolic function, however the long-term consequence in this group is unknown. Further study is required to determine the mechanism of these differences, which may be related to the effects of systemic steroids or the role of dystrophin in vascular function.

  2. Effects of Electromagnetic Fields in Spinal Muscular Atrophy: A Case Report

    NASA Astrophysics Data System (ADS)

    Cañedo, L.; Martínez-Mata, J.; Serrano-Luna, G.

    2004-09-01

    Spinal Muscular Atrophy Type I is a disease that rapidly progress to death in early infancy. A case report of a child with Werdnig-Hoffmann disease Type I that recovered at three years of age after two years exposure to electromagnetic fields (ELF) is presented. The child is now eleven years old and with the exception of slightly abnormal gait, the muscle mass of tights and gluteus, high, weight and his everyday activities correspond to those of a normal child his age. Hypothetical explanations for the effects of the electromagnetic fields are discussed.

  3. Anti-Ma2 associated paraneoplastic neurological syndrome presenting as encephalitis and progressive muscular atrophy.

    PubMed

    Waragai, M; Chiba, A; Uchibori, A; Fukushima, T; Anno, M; Tanaka, K

    2006-01-01

    A 36 year old man with a history of testicular germ cell tumour presented six months after bilateral orchidectomy with progressive amnesia, irritability, vertical gaze palsy, and generalised seizures. Eight months after initial onset of symptoms, he demonstrated a head drop with muscular atrophy of the upper limbs, shoulder girdle, and posterior neck. He reported no sensory disturbances and his sensory examination was normal. The overall clinical presentation was consistent with motor neurone disease. Cerebrospinal fluid analysis revealed mild pleocytosis and increased protein concentration. Serum and cerebrospinal fluid were positive for the anti-Ma2 antibody by western blot analysis and immunostaining. Abnormal high signal in the grey matter was noted in the cervical spinal cord and brain by T2 weighted magnetic resonance imaging (MRI). The patient was treated with corticosteroids, intravenous immunoglobulin, and antiepileptic medication. The patient improved clinically and symptom progression ceased after initiation of treatment. There was complete resolution of the abnormal brain MRI lesions; however, the cervical spinal cord MRI lesion and muscular atrophy remained unchanged. It is suggested that the anti-Ma2 antibody is involved not only in encephalitis, but may also play a role in the cervical spinal cord lesions resulting in a motor neurone disease-like presentation.

  4. Anti‐Ma2 associated paraneoplastic neurological syndrome presenting as encephalitis and progressive muscular atrophy

    PubMed Central

    Waragai, M; Chiba, A; Uchibori, A; Fukushima, T; Anno, M; Tanaka, K

    2006-01-01

    A 36 year old man with a history of testicular germ cell tumour presented six months after bilateral orchidectomy with progressive amnesia, irritability, vertical gaze palsy, and generalised seizures. Eight months after initial onset of symptoms, he demonstrated a head drop with muscular atrophy of the upper limbs, shoulder girdle, and posterior neck. He reported no sensory disturbances and his sensory examination was normal. The overall clinical presentation was consistent with motor neurone disease. Cerebrospinal fluid analysis revealed mild pleocytosis and increased protein concentration. Serum and cerebrospinal fluid were positive for the anti‐Ma2 antibody by western blot analysis and immunostaining. Abnormal high signal in the grey matter was noted in the cervical spinal cord and brain by T2 weighted magnetic resonance imaging (MRI). The patient was treated with corticosteroids, intravenous immunoglobulin, and antiepileptic medication. The patient improved clinically and symptom progression ceased after initiation of treatment. There was complete resolution of the abnormal brain MRI lesions; however, the cervical spinal cord MRI lesion and muscular atrophy remained unchanged. It is suggested that the anti‐Ma2 antibody is involved not only in encephalitis, but may also play a role in the cervical spinal cord lesions resulting in a motor neurone disease‐like presentation. PMID:16361608

  5. Spinal Muscular Atrophy (SMA)

    MedlinePlus

    ... kids of the same age or have trouble lifting things. Kids with SMA can develop scoliosis (a ... Nervous System Your Muscles Wheelchairs Scoliosis Steven's Story: Power Player Kyphosis Muscular Dystrophy Spinal Muscular Atrophy: Steven's ...

  6. Spinal Muscular Atrophy FAQ

    MedlinePlus

    ... in SMA. What is Spinal Muscular Atrophy with Respiratory Distress (SMARD)? SMARD and SMA are separate diseases ... muscle weakness and atrophy. Spinal Muscular Atrophy with Respiratory Distress (SMARD) is a rare neuromuscular disease that ...

  7. Lipogenesis mitigates dysregulated sarcoplasmic reticulum calcium uptake in muscular dystrophy.

    PubMed

    Paran, Christopher W; Zou, Kai; Ferrara, Patrick J; Song, Haowei; Turk, John; Funai, Katsuhiko

    2015-12-01

    Muscular dystrophy is accompanied by a reduction in activity of sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA) that contributes to abnormal Ca(2+) homeostasis in sarco/endoplasmic reticulum (SR/ER). Recent findings suggest that skeletal muscle fatty acid synthase (FAS) modulates SERCA activity and muscle function via its effects on SR membrane phospholipids. In this study, we examined muscle's lipid metabolism in mdx mice, a mouse model for Duchenne muscular dystrophy (DMD). De novo lipogenesis was ~50% reduced in mdx muscles compared to wildtype (WT) muscles. Gene expressions of lipogenic and other ER lipid-modifying enzymes were found to be differentially expressed between wildtype (WT) and mdx muscles. A comprehensive examination of muscles' SR phospholipidome revealed elevated phosphatidylcholine (PC) and PC/phosphatidylethanolamine (PE) ratio in mdx compared to WT mice. Studies in primary myocytes suggested that defects in key lipogenic enzymes including FAS, stearoyl-CoA desaturase-1 (SCD1), and Lipin1 are likely contributing to reduced SERCA activity in mdx mice. Triple transgenic expression of FAS, SCD1, and Lipin1 (3TG) in mdx myocytes partly rescued SERCA activity, which coincided with an increase in SR PE that normalized PC/PE ratio. These findings implicate a defect in lipogenesis to be a contributing factor for SERCA dysfunction in muscular dystrophy. Restoration of muscle's lipogenic pathway appears to mitigate SERCA function through its effects on SR membrane composition. Copyright © 2015. Published by Elsevier B.V.

  8. The use of field-inversion gel electrophoresis for deletion detection in Duchenne muscular dystrophy.

    PubMed Central

    Chen, J D; Denton, M J; Morgan, G; Pearn, J H; Mackinlay, A G

    1988-01-01

    Deletion is a common cause of Duchenne muscular dystrophy (DMD). Field-inversion gel electrophoresis, in conjunction with Southern blot hybridization, was used to detect large SfiI DNA fragments in the DMD locus. Two unrelated boys with DMD were found to have abnormal sized DNA fragments resulting from deletions. Some of the female relatives of these patients were also shown by this method to have deletions in the DMD locus. Images Figure 1 PMID:3358426

  9. Abnormal lipid metabolism in skeletal muscle tissue of patients with muscular dystrophy: In vitro, high-resolution NMR spectroscopy based observation in early phase of the disease.

    PubMed

    Srivastava, Niraj Kumar; Yadav, Ramakant; Mukherjee, Somnath; Pal, Lily; Sinha, Neeraj

    2017-05-01

    Qualitative (assignment of lipid components) and quantitative (quantification of lipid components) analysis of lipid components were performed in skeletal muscle tissue of patients with muscular dystrophy in early phase of the disease as compared to control/normal subjects. Proton nuclear magnetic resonance (NMR) spectroscopy based experiment was performed on the lipid extract of skeletal muscle tissue of patients with muscular dystrophy in early phase of the disease and normal individuals for the analysis of lipid components [triglycerides, phospholipids, total cholesterol and unsaturated fatty acids (arachidonic, linolenic and linoleic acid)]. Specimens of muscle tissue were obtained from patients with Duchenne muscular dystrophy (DMD) [n=11; Age, Mean±SD; 9.2±1.4years; all were males], Becker muscular dystrophy (BMD) [n=12; Age, Mean±SD; 21.4±5.0years; all were males], facioscapulohumeral muscular dystrophy (FSHD) [n=11; Age, Mean±SD; 23.7±7.5years; all were males] and limb girdle muscular dystrophy-2B (LGMD-2B) [n=18; Age, Mean±SD; 24.2±4.1years; all were males]. Muscle specimens were also obtained from [n=30; Mean age±SD 23.1±6.0years; all were males] normal/control subjects. Assigned lipid components in skeletal muscle tissue were triglycerides (TG), phospholipids (PL), total cholesterol (CHOL) and unsaturated fatty acids (arachidonic, linolenic and linoleic acid)]. Quantity of lipid components was observed in skeletal muscle tissue of DMD, BMD, FSHD and LGMD-2B patients as compared to control/normal subjects. TG was significantly elevated in muscle tissue of DMD, BMD and LGMD-2B patients. Increase level of CHOL was found only in muscle of DMD patients. Level of PL was found insignificant for DMD, BMD and LGMD-2B patients. Quantity of TG, PL and CHOL was unaltered in the muscle of patients with FSHD as compared to control/normal subjects. Linoleic acids were significantly reduced in muscle tissue of DMD, BMD, FSHD and LGMD-2B as compared to normal

  10. Ways of increasing muscular activity by means of isometric muscular exertion

    NASA Technical Reports Server (NTRS)

    Kovalik, A. V.

    1980-01-01

    The effect of isometric muscular exertion on the human body was investigated by having subjects perform basic movements in a sitting position in the conventional manner with additional muscle tension at 50% maximum force and at maximum force. The pulse, arterial pressure, skin temperature, respiratory rate, minute respiratory volume and electrical activity of the muscles involved were all measured. Performance of the exercises with maximum muscular exertion for 20 sec and without movement resulted in the greatest shifts in these indices; in the conventional manner substantial changes did not occur; and with isometric muscular exertion with 50% maximum force with and without movement, optimal functional shifts resulted. The latter is recommended for use in industrial exercises for the prevention of hypodynamia. Ten exercises are suggested.

  11. At the Crossroads of Clinical and Preclinical Research for Muscular Dystrophy—Are We Closer to Effective Treatment for Patients?

    PubMed Central

    Gawlik, Kinga I.

    2018-01-01

    Among diseases affecting skeletal muscle, muscular dystrophy is one of the most devastating and complex disorders. The term ‘muscular dystrophy’ refers to a heterogeneous group of genetic diseases associated with a primary muscle defect that leads to progressive muscle wasting and consequent loss of muscle function. Muscular dystrophies are accompanied by numerous clinical complications and abnormalities in other tissues that cause extreme discomfort in everyday life. The fact that muscular dystrophy often takes its toll on babies and small children, and that many patients die at a young age, adds to the cruel character of the disease. Clinicians all over the world are facing the same problem: they have no therapy to offer except for symptom-relieving interventions. Patients, their families, but also clinicians, are in urgent need of an effective cure. Despite advances in genetics, increased understanding of molecular mechanisms underlying muscle disease, despite a sweeping range of successful preclinical strategies and relative progress of their implementation in the clinic, therapy for patients is currently out of reach. Only a greater comprehension of disease mechanisms, new preclinical studies, development of novel technologies, and tight collaboration between scientists and physicians can help improve clinical treatment. Fortunately, inventiveness in research is rapidly extending the limits and setting new standards for treatment design. This review provides a synopsis of muscular dystrophy and considers the steps of preclinical and clinical research that are taking the muscular dystrophy community towards the fundamental goal of combating the traumatic disease. PMID:29772730

  12. At the Crossroads of Clinical and Preclinical Research for Muscular Dystrophy-Are We Closer to Effective Treatment for Patients?

    PubMed

    Gawlik, Kinga I

    2018-05-16

    Among diseases affecting skeletal muscle, muscular dystrophy is one of the most devastating and complex disorders. The term 'muscular dystrophy' refers to a heterogeneous group of genetic diseases associated with a primary muscle defect that leads to progressive muscle wasting and consequent loss of muscle function. Muscular dystrophies are accompanied by numerous clinical complications and abnormalities in other tissues that cause extreme discomfort in everyday life. The fact that muscular dystrophy often takes its toll on babies and small children, and that many patients die at a young age, adds to the cruel character of the disease. Clinicians all over the world are facing the same problem: they have no therapy to offer except for symptom-relieving interventions. Patients, their families, but also clinicians, are in urgent need of an effective cure. Despite advances in genetics, increased understanding of molecular mechanisms underlying muscle disease, despite a sweeping range of successful preclinical strategies and relative progress of their implementation in the clinic, therapy for patients is currently out of reach. Only a greater comprehension of disease mechanisms, new preclinical studies, development of novel technologies, and tight collaboration between scientists and physicians can help improve clinical treatment. Fortunately, inventiveness in research is rapidly extending the limits and setting new standards for treatment design. This review provides a synopsis of muscular dystrophy and considers the steps of preclinical and clinical research that are taking the muscular dystrophy community towards the fundamental goal of combating the traumatic disease.

  13. Effect of Lumbar Progressive Resistance Exercise on Lumbar Muscular Strength and Core Muscular Endurance in Soldiers.

    PubMed

    Mayer, John M; Childs, John D; Neilson, Brett D; Chen, Henian; Koppenhaver, Shane L; Quillen, William S

    2016-11-01

    Low back pain is common, costly, and disabling for active duty military personnel and veterans. The evidence is unclear on which management approaches are most effective. The purpose of this study was to assess the effectiveness of lumbar extensor high-intensity progressive resistance exercise (HIPRE) training versus control on improving lumbar extension muscular strength and core muscular endurance in soldiers. A randomized controlled trial was conducted with active duty U.S. Army Soldiers (n = 582) in combat medic training at Fort Sam Houston, Texas. Soldiers were randomized by platoon to receive the experimental intervention (lumbar extensor HIPRE training, n = 298) or control intervention (core stabilization exercise training, n = 284) at one set, one time per week, for 11 weeks. Lumbar extension muscular strength and core muscular endurance were assessed before and after the intervention period. At 11-week follow-up, lumbar extension muscular strength was 9.7% greater (p = 0.001) for HIPRE compared with control. No improvements in core muscular endurance were observed for HIPRE or control. Lumbar extensor HIPRE training is effective to improve isometric lumbar extension muscular strength in U.S. Army Soldiers. Research is needed to explore the clinical relevance of these gains. Reprint & Copyright © 2016 Association of Military Surgeons of the U.S.

  14. Myotonic Dystrophy and Facioscapulohumeral Muscular Dystrophy Registry

    ClinicalTrials.gov

    2017-08-11

    Myotonic Dystrophy; Facioscapulohumeral Muscular Dystrophy; Muscular Dystrophy; Myotonic Dystrophy Type 1; Myotonic Dystrophy Type 2; Congenital Myotonic Dystrophy; PROMM (Proximal Myotonic Myopathy); Steinert's Disease; Myotonic Muscular Dystrophy

  15. Muscular Basis of Whisker Torsion in Mice and Rats.

    PubMed

    Haidarliu, Sebastian; Bagdasarian, Knarik; Shinde, Namrata; Ahissar, Ehud

    2017-09-01

    Whisking mammals move their whiskers in the rostrocaudal and dorsoventral directions with simultaneous rolling about their long axes (torsion). Whereas muscular control of the first two types of whisker movement was already established, the anatomic muscular substrate of the whisker torsion remains unclear. Specifically, it was not clear whether torsion is induced by asymmetrical operation of known muscles or by other largely unknown muscles. Here, we report that mystacial pads of newborn and adult rats and mice contain oblique intrinsic muscles (OMs) that connect diagonally adjacent vibrissa follicles. Each of the OMs is supplied by a cluster of motor end plates. In rows A and B, OMs connect the ventral part of the rostral follicle with the dorsal part of the caudal follicle. In rows C-E, in contrast, OMs connect the dorsal part of the rostral follicle to the ventral part of the caudal follicle. This inverse architecture is consistent with previous behavioral observations [Knutsen et al.: Neuron 59 (2008) 35-42]. In newborn mice, torsion occurred in irregular single twitches. In adult anesthetized rats, microelectrode mediated electrical stimulation of an individual OM that is coupled with two adjacent whiskers was sufficient to induce a unidirectional torsion of both whiskers. Torsional movement was associated with protracting movement, indicating that in the vibrissal system, like in the ocular system, torsional movement is mechanically coupled to horizontal and vertical movements. This study shows that torsional whisker rotation is mediated by specific OMs whose morphology and attachment sites determine rotation direction and mechanical coupling, and motor innervation determines rotation dynamics. Anat Rec, 300:1643-1653, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  16. Global muscular dystrophy research: A 25-year bibliometric perspective.

    PubMed

    Ram, Shri

    2017-01-01

    Muscular dystrophy is a genetic disorder leading to progressive weakness of muscles caused due to dysfunction in or lack of protein in muscle cells. The prevalence of muscular dystrophy has been observed globally and is becoming a critical area of study for better health services. The purpose of the study is to analyze the research strength of muscular dystrophy using bibliographic literature. A quantitative literature analysis was carried out on muscular dystrophy from 1991 to 2015 for assessing the global research trends. This literature-based study was conducted using the documents retrieved from the Science Citation Index using the keywords: Duchenne Muscular Dystrophy (DMD), Becker Muscular Dystrophy (BMD), Congenital Muscular Dystrophy (CMD), Myotonic Dystrophy, Emery-Dreifuss Muscular Dystrophy, Facioscapulohumeral Muscular Dystrophy, Oculopharyngeal Muscular Dystrophy, and Limb-Girdle Muscular Dystrophy. Analysis was done for annual productivity of publication, authorship, collaboration, country performance, citation frequency, characteristics of most cited document, journal productivity, etc.

  17. Limb-Girdle Muscular Dystrophy (LGMD)

    MedlinePlus

    ... Association (MDA) is a qualified 501(c)(3) tax-exempt organization. ©2018, Muscular Dystrophy Association Inc. All ... Association (MDA) is a qualified 501(c)(3) tax-exempt organization. ©2018, Muscular Dystrophy Association Inc. All ...

  18. Long-Term Outcomes of Ataluren in Duchenne Muscular Dystrophy

    ClinicalTrials.gov

    2018-05-16

    Muscular Dystrophy, Duchenne; Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Disease; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn

  19. Carrier testing for spinal muscular atrophy

    PubMed Central

    Gitlin, Jonathan M.; Fischbeck, Kenneth; Crawford, Thomas O.; Cwik, Valerie; Fleischman, Alan; Gonye, Karla; Heine, Deborah; Hobby, Kenneth; Kaufmann, Petra; Keiles, Steven; MacKenzie, Alex; Musci, Thomas; Prior, Thomas; Lloyd-Puryear, Michele; Sugarman, Elaine A.; Terry, Sharon F.; Urv, Tiina; Wang, Ching; Watson, Michael; Yaron, Yuval; Frosst, Phyllis; Howell, R. Rodney

    2014-01-01

    Spinal muscular atrophy is the most common fatal hereditary disease among newborns and infants. There is as yet no effective treatment. Although a carrier test is available, currently there is disagreement among professional medical societies who proffer standards of care as to whether or not carrier screening for spinal muscular atrophy should be offered as part of routine reproductive care. This leaves health care providers without clear guidance. In fall 2009, a meeting was held by National Institutes of Health to examine the scientific basis for spinal muscular atrophy carrier screening and to consider the issues that accompany such screening. In this article, the meeting participants summarize the discussions and conclude that pan-ethnic carrier screening for spinal muscular atrophy is technically feasible and that the specific study of implementing a spinal muscular atrophy carrier screening program raises broader issues about determining the scope and specifics of carrier screening in general. PMID:20808230

  20. A Novel Lamin A Mutant Responsible for Congenital Muscular Dystrophy Causes Distinct Abnormalities of the Cell Nucleus.

    PubMed

    Barateau, Alice; Vadrot, Nathalie; Vicart, Patrick; Ferreiro, Ana; Mayer, Michèle; Héron, Delphine; Vigouroux, Corinne; Buendia, Brigitte

    2017-01-01

    A-type lamins, the intermediate filament proteins participating in nuclear structure and function, are encoded by LMNA. LMNA mutations can lead to laminopathies such as lipodystrophies, premature aging syndromes (progeria) and muscular dystrophies. Here, we identified a novel heterozygous LMNA p.R388P de novo mutation in a patient with a non-previously described severe phenotype comprising congenital muscular dystrophy (L-CMD) and lipodystrophy. In culture, the patient's skin fibroblasts entered prematurely into senescence, and some nuclei showed a lamina honeycomb pattern. C2C12 myoblasts were transfected with a construct carrying the patient's mutation; R388P-lamin A (LA) predominantly accumulated within the nucleoplasm and was depleted at the nuclear periphery, altering the anchorage of the inner nuclear membrane protein emerin and the nucleoplasmic protein LAP2-alpha. The mutant LA triggered a frequent and severe nuclear dysmorphy that occurred independently of prelamin A processing, as well as increased histone H3K9 acetylation. Nuclear dysmorphy was not significantly improved when transfected cells were treated with drugs disrupting microtubules or actin filaments or modifying the global histone acetylation pattern. Therefore, releasing any force exerted at the nuclear envelope by the cytoskeleton or chromatin did not rescue nuclear shape, in contrast to what was previously shown in Hutchinson-Gilford progeria due to other LMNA mutations. Our results point to the specific cytotoxic effect of the R388P-lamin A mutant, which is clinically related to a rare and severe multisystemic laminopathy phenotype.

  1. Wasting Mechanisms in Muscular Dystrophy

    PubMed Central

    Shin, Jonghyun; Tajrishi, Marjan M.; Ogura, Yuji; Kumar, Ashok

    2013-01-01

    Muscular dystrophy is a group of more than 30 different clinical genetic disorders that are characterized by progressive skeletal muscle wasting and degeneration. Primary deficiency of specific extracellular matrix, sarcoplasmic, cytoskeletal, or nuclear membrane protein results in several secondary changes such as sarcolemmal instability, calcium influx, fiber necrosis, oxidative stress, inflammatory response, breakdown of extracellular matrix, and eventually fibrosis which leads to loss of ambulance and cardiac and respiratory failure. A number of molecular processes have now been identified which hasten disease progression in human patients and animal models of muscular dystrophy. Accumulating evidence further suggests that aberrant activation of several signaling pathways aggravate pathological cascades in dystrophic muscle. Although replacement of defective gene with wild-type is paramount to cure, management of secondary pathological changes has enormous potential to improving the quality of life and extending lifespan of muscular dystrophy patients. In this article, we have reviewed major cellular and molecular mechanisms leading to muscle wasting in muscular dystrophy. PMID:23669245

  2. Physiology of respiratory disturbances in muscular dystrophies

    PubMed Central

    Lo Mauro, Antonella

    2016-01-01

    Muscular dystrophy is a group of inherited myopathies characterised by progressive skeletal muscle wasting, including of the respiratory muscles. Respiratory failure, i.e. when the respiratory system fails in its gas exchange functions, is a common feature in muscular dystrophy, being the main cause of death, and it is a consequence of lung failure, pump failure or a combination of the two. The former is due to recurrent aspiration, the latter to progressive weakness of respiratory muscles and an increase in the load against which they must contract. In fact, both the resistive and elastic components of the work of breathing increase due to airway obstruction and chest wall and lung stiffening, respectively. The respiratory disturbances in muscular dystrophy are restrictive pulmonary function, hypoventilation, altered thoracoabdominal pattern, hypercapnia, dyspnoea, impaired regulation of breathing, inefficient cough and sleep disordered breathing. They can be present at different rates according to the type of muscular dystrophy and its progression, leading to different onset of each symptom, prognosis and degree of respiratory involvement. Key points A common feature of muscular dystrophy is respiratory failure, i.e. the inability of the respiratory system to provide proper oxygenation and carbon dioxide elimination. In the lung, respiratory failure is caused by recurrent aspiration, and leads to hypoxaemia and hypercarbia. Ventilatory failure in muscular dystrophy is caused by increased respiratory load and respiratory muscles weakness. Respiratory load increases in muscular dystrophy because scoliosis makes chest wall compliance decrease, atelectasis and fibrosis make lung compliance decrease, and airway obstruction makes airway resistance increase. The consequences of respiratory pump failure are restrictive pulmonary function, hypoventilation, altered thoracoabdominal pattern, hypercapnia, dyspnoea, impaired regulation of breathing, inefficient cough and

  3. Physiology of respiratory disturbances in muscular dystrophies.

    PubMed

    Lo Mauro, Antonella; Aliverti, Andrea

    2016-12-01

    Muscular dystrophy is a group of inherited myopathies characterised by progressive skeletal muscle wasting, including of the respiratory muscles. Respiratory failure, i.e . when the respiratory system fails in its gas exchange functions, is a common feature in muscular dystrophy, being the main cause of death, and it is a consequence of lung failure, pump failure or a combination of the two. The former is due to recurrent aspiration, the latter to progressive weakness of respiratory muscles and an increase in the load against which they must contract. In fact, both the resistive and elastic components of the work of breathing increase due to airway obstruction and chest wall and lung stiffening, respectively. The respiratory disturbances in muscular dystrophy are restrictive pulmonary function, hypoventilation, altered thoracoabdominal pattern, hypercapnia, dyspnoea, impaired regulation of breathing, inefficient cough and sleep disordered breathing. They can be present at different rates according to the type of muscular dystrophy and its progression, leading to different onset of each symptom, prognosis and degree of respiratory involvement. A common feature of muscular dystrophy is respiratory failure, i.e. the inability of the respiratory system to provide proper oxygenation and carbon dioxide elimination.In the lung, respiratory failure is caused by recurrent aspiration, and leads to hypoxaemia and hypercarbia.Ventilatory failure in muscular dystrophy is caused by increased respiratory load and respiratory muscles weakness.Respiratory load increases in muscular dystrophy because scoliosis makes chest wall compliance decrease, atelectasis and fibrosis make lung compliance decrease, and airway obstruction makes airway resistance increase.The consequences of respiratory pump failure are restrictive pulmonary function, hypoventilation, altered thoracoabdominal pattern, hypercapnia, dyspnoea, impaired regulation of breathing, inefficient cough and sleep disordered

  4. Muscular dystrophy

    MedlinePlus

    ... are no known cures for the various muscular dystrophies. The goal of treatment is to control symptoms. Physical therapy may help maintain muscle strength and function. Leg braces and a wheelchair ...

  5. Repression of phosphatidylinositol transfer protein α ameliorates the pathology of Duchenne muscular dystrophy.

    PubMed

    Vieira, Natassia M; Spinazzola, Janelle M; Alexander, Matthew S; Moreira, Yuri B; Kawahara, Genri; Gibbs, Devin E; Mead, Lillian C; Verjovski-Almeida, Sergio; Zatz, Mayana; Kunkel, Louis M

    2017-06-06

    Duchenne muscular dystrophy (DMD) is a progressive muscle wasting disease caused by X-linked inherited mutations in the DYSTROPHIN ( DMD ) gene. Absence of dystrophin protein from the sarcolemma causes severe muscle degeneration, fibrosis, and inflammation, ultimately leading to cardiorespiratory failure and premature death. Although there are several promising strategies under investigation to restore dystrophin protein expression, there is currently no cure for DMD, and identification of genetic modifiers as potential targets represents an alternative therapeutic strategy. In a Brazilian golden retriever muscular dystrophy (GRMD) dog colony, two related dogs demonstrated strikingly mild dystrophic phenotypes compared with those typically observed in severely affected GRMD dogs despite lacking dystrophin. Microarray analysis of these "escaper" dogs revealed reduced expression of phosphatidylinositol transfer protein-α ( PITPNA ) in escaper versus severely affected GRMD dogs. Based on these findings, we decided to pursue investigation of modulation of PITPNA expression on dystrophic pathology in GRMD dogs, dystrophin-deficient sapje zebrafish, and human DMD myogenic cells. In GRMD dogs, decreased expression of Pitpna was associated with increased phosphorylated Akt (pAkt) expression and decreased PTEN levels. PITPNA knockdown by injection of morpholino oligonucleotides in sapje zebrafish also increased pAkt, rescued the abnormal muscle phenotype, and improved long-term sapje mutant survival. In DMD myotubes, PITPNA knockdown by lentiviral shRNA increased pAkt and increased myoblast fusion index. Overall, our findings suggest PIPTNA as a disease modifier that accords benefits to the abnormal signaling, morphology, and function of dystrophic skeletal muscle, and may be a target for DMD and related neuromuscular diseases.

  6. Repression of phosphatidylinositol transfer protein α ameliorates the pathology of Duchenne muscular dystrophy

    PubMed Central

    Vieira, Natassia M.; Spinazzola, Janelle M.; Alexander, Matthew S.; Moreira, Yuri B.; Kawahara, Genri; Gibbs, Devin E.; Mead, Lillian C.; Zatz, Mayana; Kunkel, Louis M.

    2017-01-01

    Duchenne muscular dystrophy (DMD) is a progressive muscle wasting disease caused by X-linked inherited mutations in the DYSTROPHIN (DMD) gene. Absence of dystrophin protein from the sarcolemma causes severe muscle degeneration, fibrosis, and inflammation, ultimately leading to cardiorespiratory failure and premature death. Although there are several promising strategies under investigation to restore dystrophin protein expression, there is currently no cure for DMD, and identification of genetic modifiers as potential targets represents an alternative therapeutic strategy. In a Brazilian golden retriever muscular dystrophy (GRMD) dog colony, two related dogs demonstrated strikingly mild dystrophic phenotypes compared with those typically observed in severely affected GRMD dogs despite lacking dystrophin. Microarray analysis of these “escaper” dogs revealed reduced expression of phosphatidylinositol transfer protein-α (PITPNA) in escaper versus severely affected GRMD dogs. Based on these findings, we decided to pursue investigation of modulation of PITPNA expression on dystrophic pathology in GRMD dogs, dystrophin-deficient sapje zebrafish, and human DMD myogenic cells. In GRMD dogs, decreased expression of Pitpna was associated with increased phosphorylated Akt (pAkt) expression and decreased PTEN levels. PITPNA knockdown by injection of morpholino oligonucleotides in sapje zebrafish also increased pAkt, rescued the abnormal muscle phenotype, and improved long-term sapje mutant survival. In DMD myotubes, PITPNA knockdown by lentiviral shRNA increased pAkt and increased myoblast fusion index. Overall, our findings suggest PIPTNA as a disease modifier that accords benefits to the abnormal signaling, morphology, and function of dystrophic skeletal muscle, and may be a target for DMD and related neuromuscular diseases. PMID:28533404

  7. Muscular Oxygen Uptake Kinetics in Aged Adults.

    PubMed

    Koschate, J; Drescher, U; Baum, K; Eichberg, S; Schiffer, T; Latsch, J; Brixius, K; Hoffmann, U

    2016-06-01

    Pulmonary oxygen uptake (V˙O2) kinetics and heart rate kinetics are influenced by age and fitness. Muscular V˙O2 kinetics can be estimated from heart rate and pulmonary V˙O2. In this study the applicability of a test using pseudo-random binary sequences in combination with a model to estimate muscular V˙O2 kinetics was tested. Muscular V˙O2 kinetics were expected to be faster than pulmonary V˙O2 kinetics, slowed in aged subjects and correlated with maximum V˙O2 and heart rate kinetics. 27 elderly subjects (73±3 years; 81.1±8.2 kg; 175±4.7 cm) participated. Cardiorespiratory kinetics were assessed using the maximum of cross-correlation functions, higher maxima implying faster kinetics. Muscular V˙O2 kinetics were faster than pulmonary V˙O2 kinetics (0.31±0.1 vs. 0.29±0.1 s; p=0.004). Heart rate kinetics were not correlated with muscular or pulmonary V˙O2 kinetics or maximum V˙O2. Muscular V˙O2 kinetics correlated with maximum V˙O2 (r=0.35; p=0.033). This suggests, that muscular V˙O2 kinetics are faster than estimates from pulmonary V˙O2 and related to maximum V˙O2 in aged subjects. In the future this experimental approach may help to characterize alterations in muscular V˙O2 under various conditions independent of motivation and maximal effort. © Georg Thieme Verlag KG Stuttgart · New York.

  8. Implications of white striping and spaghetti meat abnormalities on meat quality and histological features in broilers.

    PubMed

    Baldi, G; Soglia, F; Mazzoni, M; Sirri, F; Canonico, L; Babini, E; Laghi, L; Cavani, C; Petracci, M

    2018-01-01

    During the past few years, there has been an increasing prevalence of broiler breast muscle abnormalities, such as white striping (WS) and wooden breast conditions. More recently, a new muscular abnormality termed as spaghetti meat (SM) because of the altered structural integrity of the Pectoralis major muscle often associated with WS has emerged. Thus, this study aimed at evaluating the effects of WS and SM conditions, occurring alone or combined within the same P. major muscle, on meat quality traits and muscle histology. In two replications, 96 P. major muscles were classified into four classes: normal (N), WS, SM and WS/SM. The whole fillet was used for weight assessment and morphometric measurements, then each sample was cut in order to separate the superficial layer from the deep one and used to evaluate proximate composition, histological features, nuclear magnetic resonance relaxation times, functional properties and both myofibrillar and sarcoplasmic proteins profile. Fillets affected by WS and SM abnormalities exhibited higher weights and increased thickness and length. SM condition was associated with a relevant decrease in protein content coupled with a significant increase in moisture level, whereas fat content was affected only by the simultaneous presence of WS. Histological evaluations revealed that abnormal samples were characterized by several degenerative aspects that almost completely concerned the superficial layer of the fillets. White striped fillets exhibited necrosis and lysis of fibers, fibrosis, lipidosis, loss of cross striation and vacuolar degeneration. Moreover, SM samples were characterized by poor fiber uniformity and a progressive rarefaction of the endo- and peri-mysial connective tissue, whereas WS/SM fillets showed intermediate histological features. Nuclear magnetic resonance relaxation analysis revealed a higher proportion of extra-myofibrillar water in the superficial section of all the abnormal fillets, especially in SM

  9. Dystroglycan and muscular dystrophies related to the dystrophin-glycoprotein complex.

    PubMed

    Sciandra, Francesca; Bozzi, Manuela; Bianchi, Marzia; Pavoni, Ernesto; Giardina, Bruno; Brancaccio, Andrea

    2003-01-01

    Dystroglycan (DG) is an adhesion molecule composed of two subunits, alpha and beta, that are produced by the post-translational cleavage of a single precursor molecule. DG is a pivotal component of the dystrophin-glycoprotein complex (DGC), which connects the extracellular matrix to the cytoskeleton in skeletal muscle and many other tissues. Some muscular dystrophies are caused by mutations of DGC components, such as dystrophin, sarcoglycan or laminin-2, or also of DGC-associated molecules, such as caveolin-3. DG-null mice died during early embriogenesis and no neuromuscular diseases directly associated to genetic abnormalities of DG were identified so far. However, DG plays a crucial role for muscle integrity since its targeting at the sarcolemma is often perturbed in DGC-related neuromuscular disorders.

  10. Mutations in GDP-mannose pyrophosphorylase B cause congenital and limb-girdle muscular dystrophies associated with hypoglycosylation of α-dystroglycan.

    PubMed

    Carss, Keren J; Stevens, Elizabeth; Foley, A Reghan; Cirak, Sebahattin; Riemersma, Moniek; Torelli, Silvia; Hoischen, Alexander; Willer, Tobias; van Scherpenzeel, Monique; Moore, Steven A; Messina, Sonia; Bertini, Enrico; Bönnemann, Carsten G; Abdenur, Jose E; Grosmann, Carla M; Kesari, Akanchha; Punetha, Jaya; Quinlivan, Ros; Waddell, Leigh B; Young, Helen K; Wraige, Elizabeth; Yau, Shu; Brodd, Lina; Feng, Lucy; Sewry, Caroline; MacArthur, Daniel G; North, Kathryn N; Hoffman, Eric; Stemple, Derek L; Hurles, Matthew E; van Bokhoven, Hans; Campbell, Kevin P; Lefeber, Dirk J; Lin, Yung-Yao; Muntoni, Francesco

    2013-07-11

    Congenital muscular dystrophies with hypoglycosylation of α-dystroglycan (α-DG) are a heterogeneous group of disorders often associated with brain and eye defects in addition to muscular dystrophy. Causative variants in 14 genes thought to be involved in the glycosylation of α-DG have been identified thus far. Allelic mutations in these genes might also cause milder limb-girdle muscular dystrophy phenotypes. Using a combination of exome and Sanger sequencing in eight unrelated individuals, we present evidence that mutations in guanosine diphosphate mannose (GDP-mannose) pyrophosphorylase B (GMPPB) can result in muscular dystrophy variants with hypoglycosylated α-DG. GMPPB catalyzes the formation of GDP-mannose from GTP and mannose-1-phosphate. GDP-mannose is required for O-mannosylation of proteins, including α-DG, and it is the substrate of cytosolic mannosyltransferases. We found reduced α-DG glycosylation in the muscle biopsies of affected individuals and in available fibroblasts. Overexpression of wild-type GMPPB in fibroblasts from an affected individual partially restored glycosylation of α-DG. Whereas wild-type GMPPB localized to the cytoplasm, five of the identified missense mutations caused formation of aggregates in the cytoplasm or near membrane protrusions. Additionally, knockdown of the GMPPB ortholog in zebrafish caused structural muscle defects with decreased motility, eye abnormalities, and reduced glycosylation of α-DG. Together, these data indicate that GMPPB mutations are responsible for congenital and limb-girdle muscular dystrophies with hypoglycosylation of α-DG. Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  11. Muscular Dystrophy

    MedlinePlus

    ... forms of MD grow worse as the person's muscles get weaker. Most people with MD eventually lose the ability to walk. There is no cure for muscular dystrophy. Treatments can help with the symptoms and prevent complications. ...

  12. The stiff-man syndrome: new pathophysiological aspects from abnormal exteroceptive reflexes and the response to clomipramine, clonidine, and tizanidine.

    PubMed Central

    Meinck, H M; Ricker, K; Conrad, B

    1984-01-01

    Neurophysiological investigations of a patient suffering from the stiff-man syndrome revealed that exteroceptive reflexes, in particular those elicited from the skin, were excessively enhanced. In contrast, no abnormalities were found within the monosynaptic reflex arc. Clomipramine injection severely aggravated the clinical symptoms whereas diazepam, clonidine, and tizanidine decreased both muscular stiffness and abnormal exteroceptive reflexes. The hypothesis is put forward that the stiff-man syndrome is a disorder of descending brain-stem systems which exert a net inhibitory control on axial and limb girdle muscle tone as well as on exteroceptive reflex transmission. Detection of abnormal exteroceptive reflex activity in conjunction with neuropharmacological testing might help in the diagnosis of this rare disease. PMID:6707674

  13. Muscular Dystrophy

    MedlinePlus

    ... be affected. Limb-girdle muscular dystrophy (LGMD) affects boys and girls equally, weakening muscles in the shoulders and upper ... weakness and poor muscle tone. Occurring in both girls and boys, it can have different symptoms. It varies in ...

  14. Gains in flexibility related to measures of muscular performance: impact of flexibility on muscular performance.

    PubMed

    Ferreira, Gustavo Nunes Tasca; Teixeira-Salmela, Luci Fuscaldi; Guimarães, Cristiano Queiroz

    2007-07-01

    Studies that investigated possible correlations between flexibility and muscular performance are scarce in the literature. Therefore, the purpose of this study was to investigate the impact of a program of static stretching on the flexibility of the hamstrings and on muscular performance of the knee flexors and extensors. Pre-post experimental design. University laboratory. Thirty subjects aged 22.8 +/- 4.9 years with bilaterally shortened hamstrings. Using a protocol that has been previously described, the intervention consisted of 30 sessions of static stretching, performed bilaterally five times a week for 6 weeks. Measures of knee range of motion and isokinetic muscular performance (peak torque, angle of peak torque, and work) of knee flexors and extensors at speeds of 60 and 300 degrees/s. After intervention, significant gains in measures of flexibility (P < 0.0001) were observed, with an average gain of the knee-extension angle of 12.6 degrees, ranging from -1.2 to 30.7 degrees. In addition, we found significant increases in the following parameters of muscular performance: angle of peak torque of hamstrings at 60 and 300 degrees/s (P < 0.0001 and 0.018) and for work at 60 and 300 degrees/s for knee flexors (P = 0.012 and 0.005) and for knee extensors (P < 0.0001). The intervention resulted in gains in measures of flexibility, and these gains had a positive impact on some parameters of muscular performance.

  15. Translational Research for Muscular Dystrophy

    DTIC Science & Technology

    2012-05-01

    common in-frame deletions for which clinical information from human Becker muscular dystrophy patients (deletion of exons 44-45, 49-51, 48-53) is lacking... Dystrophy PRINCIPAL INVESTIGATOR: Gregory A. Cox, Ph.D. CONTRACTING ORGANIZATION: The Jackson Laboratory...REPORT TYPE Annual 3. DATES COVERED 1 MAR 2011 - 30 APR 2012 4. TITLE AND SUBTITLE Translational Research for Muscular Dystrophy 5a. CONTRACT

  16. Three novel serum biomarkers, miR-1, miR-133a, and miR-206 for Limb-girdle muscular dystrophy, Facioscapulohumeral muscular dystrophy, and Becker muscular dystrophy.

    PubMed

    Matsuzaka, Yasunari; Kishi, Soichiro; Aoki, Yoshitsugu; Komaki, Hirofumi; Oya, Yasushi; Takeda, Shin-Ichi; Hashido, Kazuo

    2014-11-01

    Muscular dystrophies are a clinically and genetically heterogeneous group of inherited myogenic disorders. In clinical tests for these diseases, creatine kinase (CK) is generally used as diagnostic blood-based biomarker. However, because CK levels can be altered by various other factors, such as vigorous exercise, etc., false positive is observed. Therefore, three microRNAs (miRNAs), miR-1, miR-133a, and miR-206, were previously reported as alternative biomarkers for duchenne muscular dystrophy (DMD). However, no alternative biomarkers have been established for the other muscular dystrophies. We, therefore, evaluated whether these miR-1, miR-133a, and miR-206 can be used as powerful biomarkers using the serum from muscular dystrophy patients including DMD, myotonic dystrophy 1 (DM1), limb-girdle muscular dystrophy (LGMD), facioscapulohumeral muscular dystrophy (FSHD), becker muscular dystrophy (BMD), and distal myopathy with rimmed vacuoles (DMRV) by qualitative polymerase chain reaction (PCR) amplification assay. Statistical analysis indicated that all these miRNA levels in serum represented no significant differences between all muscle disorders examined in this study and controls by Bonferroni correction. However, some of these indicated significant differences without correction for testing multiple diseases (P < 0.05). The median values of miR-1 levels in the serum of patients with LGMD, FSHD, and BMD were approximately 5.5, 3.3 and 1.7 compared to that in controls, 0.68, respectively. Similarly, those of miR-133a and miR-206 levels in the serum of BMD patients were about 2.5 and 2.1 compared to those in controls, 1.03 and 1.32, respectively. Taken together, our data demonstrate that levels of miR-1, miR-133a, and miR-206 in serum of BMD and miR-1 in sera of LGMD and FSHD patients showed no significant differences compared with those of controls by Bonferroni correction. However, the results might need increase in sample sizes to evaluate these three miRNAs as

  17. Co-induction of the heat shock response ameliorates disease progression in a mouse model of human spinal and bulbar muscular atrophy: implications for therapy

    PubMed Central

    Malik, Bilal; Nirmalananthan, Niranjanan; Gray, Anna L.; La Spada, Albert R.; Hanna, Michael G.

    2013-01-01

    Spinal and bulbar muscular atrophy, also known as Kennedy’s disease, is an adult-onset hereditary neurodegenerative disorder caused by an expansion of the polyglutamine repeat in the first exon in the androgen receptor gene. Pathologically, the disease is defined by selective loss of spinal and bulbar motor neurons causing bulbar, facial and limb weakness. Although the precise disease pathophysiology is largely unknown, it appears to be related to abnormal accumulation of the pathogenic androgen receptor protein within the nucleus, leading to disruption of cellular processes. Using a mouse model of spinal and bulbar muscular atrophy that exhibits many of the characteristic features of the human disease, in vivo physiological assessment of muscle function revealed that mice with the pathogenic expansion of the androgen receptor develop a motor deficit characterized by a reduction in muscle force, abnormal muscle contractile characteristics, loss of functional motor units and motor neuron degeneration. We have previously shown that treatment with arimoclomol, a co-inducer of the heat shock stress response, delays disease progression in the mutant superoxide dismutase 1 mouse model of amyotrophic lateral sclerosis, a fatal motor neuron disease. We therefore evaluated the therapeutic potential of arimoclomol in mice with spinal and bulbar muscular atrophy. Arimoclomol was administered orally, in drinking water, from symptom onset and the effects established at 18 months of age, a late stage of disease. Arimoclomol significantly improved hindlimb muscle force and contractile characteristics, rescued motor units and, importantly, improved motor neuron survival and upregulated the expression of the vascular endothelial growth factor which possess neurotrophic activity. These results provide evidence that upregulation of the heat shock response by treatment with arimoclomol may have therapeutic potential in the treatment of spinal and bulbar muscular atrophy and may also

  18. Imaging diagnosis--muscular hypertrophy of the small intestine and pseudodiverticula in a horse.

    PubMed

    Navas De Solís, Cristobal; Biscoe, Elisabeth W; Lund, Caleb M; Labbe, Karyn; Muñoz, Juan; Farnsworth, Kelly

    2015-01-01

    A 14-year-old Thoroughbred gelding was presented for chronic colic and weight loss. Transcutaneous and transrectal abdominal ultrasonography revealed distended, thickened small intestine with primary thickening of the muscularis and a focally more thickened loop with an echoic structure crossing the wall from the mucosa to the serosa. Visualization of diffuse thickening of the muscularis (muscular hypertrophy of the small intestine) and a focal lesion (pseudodiverticulum) helped clinicians make informed decisions. This case illustrates the importance of transabdominal and transrectal ultrasonography in horses with chronic colic and the relevance of considering the abnormalities in layering pattern of the intestinal wall. © 2014 American College of Veterinary Radiology.

  19. Abnormal resting-state cortical coupling in chronic tinnitus

    PubMed Central

    Schlee, Winfried; Hartmann, Thomas; Langguth, Berthold; Weisz, Nathan

    2009-01-01

    Background Subjective tinnitus is characterized by an auditory phantom perception in the absence of any physical sound source. Consequently, in a quiet environment, tinnitus patients differ from control participants because they constantly perceive a sound whereas controls do not. We hypothesized that this difference is expressed by differential activation of distributed cortical networks. Results The analysis was based on a sample of 41 participants: 21 patients with chronic tinnitus and 20 healthy control participants. To investigate the architecture of these networks, we used phase locking analysis in the 1–90 Hz frequency range of a minute of resting-state MEG recording. We found: 1) For tinnitus patients: A significant decrease of inter-areal coupling in the alpha (9–12 Hz) band and an increase of inter-areal coupling in the 48–54 Hz gamma frequency range relative to the control group. 2) For both groups: an inverse relationship (r = -.71) of the alpha and gamma network coupling. 3) A discrimination of 83% between the patient and the control group based on the alpha and gamma networks. 4) An effect of manifestation on the distribution of the gamma network: In patients with a tinnitus history of less than 4 years, the left temporal cortex was predominant in the gamma network whereas in patients with tinnitus duration of more than 4 years, the gamma network was more widely distributed including more frontal and parietal regions. Conclusion In the here presented data set we found strong support for an alteration of long-range coupling in tinnitus. Long-range coupling in the alpha frequency band was decreased for tinnitus patients while long-range gamma coupling was increased. These changes discriminate well between tinnitus and control participants. We propose a tinnitus model that integrates this finding in the current knowledge about tinnitus. Furthermore we discuss the impact of this finding to tinnitus therapies using Transcranial Magnetic Stimulation

  20. Loss of Drosophila A-type lamin C initially causes tendon abnormality including disintegration of cytoskeleton and nuclear lamina in muscular defects.

    PubMed

    Uchino, Ryo; Nonaka, Yu-Ki; Horigome, Tuneyoshi; Sugiyama, Shin; Furukawa, Kazuhiro

    2013-01-01

    Lamins are the major components of nuclear envelope architecture, being required for both the structural and informational roles of the nuclei. Mutations of lamins cause a spectrum of diseases in humans, including muscular dystrophy. We report here that the loss of the A-type lamin gene, lamin C in Drosophila resulted in pupal metamorphic lethality caused by tendon defects, matching the characteristics of human A-type lamin revealed by Emery-Dreifuss muscular dystrophy (EDMD). In tendon cells lacking lamin C activity, overall cell morphology was affected and organization of the spectraplakin family cytoskeletal protein Shortstop which is prominently expressed in tendon cells gradually disintegrated, notably around the nucleus and in a manner correlating well with the degradation of musculature. Furthermore, lamin C null mutants were efficiently rescued by restoring lamin C expression to shortstop-expressing cells, which include tendon cells but exclude skeletal muscle cells. Thus the critical function of A-type lamin C proteins in Drosophila musculature is to maintain proper function and morphology of tendon cells. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. Translational Research for Muscular Dystrophy

    DTIC Science & Technology

    2014-05-01

    year of work was awarded to allow completion of our transgenic analysis of Becker -like muscular dystrophy rescue experiments, allow completion of the D2... Dystrophy PRINCIPAL INVESTIGATOR: Gregory A. Cox, Ph.D. CONTRACTING ORGANIZATION: The Jackson Laboratory Bar Harbor, ME 04609-1523...April 2014 4. TITLE AND SUBTITLE Translational Research for Muscular Dystrophy 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-11-1-0330 5c

  2. Parental attitudes toward newborn screening for Duchenne/Becker muscular dystrophy and spinal muscular atrophy.

    PubMed

    Wood, Molly F; Hughes, Sarah C; Hache, Lauren P; Naylor, Edwin W; Abdel-Hamid, Hoda Z; Barmada, M Michael; Dobrowolski, Steven F; Stickler, David E; Clemens, Paula R

    2014-06-01

    Disease inclusion in the newborn screening (NBS) panel should consider the opinions of those most affected by the outcome of screening. We assessed the level and factors that affect parent attitudes regarding NBS panel inclusion of Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), and spinal muscular atrophy (SMA). The attitudes toward NBS for DMD, BMD, and SMA were surveyed and compared for 2 categories of parents, those with children affected with DMD, BMD, or SMA and expectant parents unselected for known family medical history. The level of support for NBS for DMD, BMD, and SMA was 95.9% among parents of children with DMD, BMD, or SMA and 92.6% among expectant parents. There was strong support for NBS for DMD, BMD, and SMA in both groups of parents. Given advances in diagnostics and promising therapeutic approaches, discussion of inclusion in NBS should continue. Copyright © 2013 Wiley Periodicals, Inc.

  3. Physical Therapy and Facioscapulohumeral Muscular Dystrophy (FSHD)

    MedlinePlus

    ... 43. 2. The FSH‐DY Group. A prospective, quantitative study of the natural history of facioscapulohumeral muscular ... regarding facioscapulohumeral muscular dystrophy (FSHD). It actively promotes research toward the prevention, cause and treatment of FSHD. ...

  4. [Myostatin blockade therapy for muscular atrophy].

    PubMed

    Sunada, Yoshihide

    2011-11-01

    Myostatin, a member of the muscle-specific transforming growth factor (TGF)-β family, negatively regulates skeletal muscle growth. It inhibits muscle stem cell proliferation and differentiation and attenuates adult muscle fiber protein accretion, resulting in decreased skeletal muscle mass. As such, it has been considered a therapeutic target of muscular dystrophy. Notably, administration of a blocking antibody against myostatin ameliorated the pathophysiology of dystrophin-deficient mdx mice. Although a clinical trial of anti-myostatin antibody MYO-029 failed to achieve a significant outcome in patients with muscular dystrophies, various distinct approaches have been taken to establish anti-myostatin therapy, including myostatin decoy receptor ACE-031, small-molecule inhibitors against the myostatin receptor, and myostatin short intertering RNA with collagen-derived carrier particles. The clinical application of anti-myostatin therapeutics in treatment of patients with muscular dystrophy needs further evaluation for safety and specification of the target disease types among the various muscular dystrophies. In addition, myostatin inhibition could be effective for muscle-wasting conditions other than muscular dystrophy- for instance, steroid-induced myopathy, mitochondrial myopathy, or sarcopenia in elderly patients. Moreover, considerable evidence shows that myostatin regulates energy metabolism and that its inhibition can significantly attenuate the progression of obesity and diabetes. It may also be applicable for the prevention of metabolic syndrome. Thus, safe and potent anti-myostatin therapy will have a wide variety of applications in modern medicine.

  5. Muscular Dystrophy Surveillance Tracking and Research Network (MD STARnet): case definition in surveillance for childhood-onset Duchenne/Becker muscular dystrophy.

    PubMed

    Mathews, Katherine D; Cunniff, Chris; Kantamneni, Jiji R; Ciafaloni, Emma; Miller, Timothy; Matthews, Dennis; Cwik, Valerie; Druschel, Charlotte; Miller, Lisa; Meaney, F John; Sladky, John; Romitti, Paul A

    2010-09-01

    The Muscular Dystrophy Surveillance Tracking and Research Network (MD STARnet) is a multisite collaboration to determine the prevalence of childhood-onset Duchenne/Becker muscular dystrophy and to characterize health care and health outcomes in this population. MD STARnet uses medical record abstraction to identify patients with Duchenne/Becker muscular dystrophy born January 1, 1982 or later who resided in 1 of the participating sites. Critical diagnostic elements of each abstracted record are reviewed independently by >4 clinicians and assigned to 1 of 6 case definition categories (definite, probable, possible, asymptomatic, female, not Duchenne/Becker muscular dystrophy) by consensus. As of November 2009, 815 potential cases were reviewed. Of the cases included in analysis, 674 (82%) were either ''definite'' or ''probable'' Duchenne/Becker muscular dystrophy. These data reflect a change in diagnostic testing, as case assignment based on genetic testing increased from 67% in the oldest cohort (born 1982-1987) to 94% in the cohort born 2004 to 2009.

  6. Muscular Dystrophy Surveillance Tracking and Research Network (MD STARnet): Case Definition in Surveillance for Childhood-Onset Duchenne/Becker Muscular Dystrophy

    PubMed Central

    Mathews, Katherine D.; Cunniff, Chris; Kantamneni, Jiji R.; Ciafaloni, Emma; Miller, Timothy; Matthews, Dennis; Cwik, Valerie; Druschel, Charlotte; Miller, Lisa; Meaney, F. John; Sladky, John; Romitti, Paul A.

    2013-01-01

    The Muscular Dystrophy Surveillance Tracking and Research Network (MD STARnet) is a multisite collaboration to determine the prevalence of childhood-onset Duchenne/Becker muscular dystrophy and to characterize health care and health outcomes in this population. MD STARnet uses medical record abstraction to identify patients with Duchenne/Becker muscular dystrophy born January 1, 1982 or later who resided in one of the participating sites. Critical diagnostic elements of each abstracted record are reviewed independently by ≥4 clinicians and assigned to 1 of 6 case definition categories (definite, probable, possible, asymptomatic, female, not Duchenne/Becker muscular dystrophy) by consensus. As of November 2009, 815 potential cases were reviewed. Of the cases included in analysis, 674 (82%) were either “definite” or “probable” Duchenne/Becker muscular dystrophy. These data reflect a change in diagnostic testing, as case assignment based on genetic testing increased from 67% in the oldest cohort (born 1982–1987) to 94% in the cohort born 2004–2009. PMID:20817884

  7. Dysfunction of the neuromuscular junction in spinal muscular atrophy types 2 and 3.

    PubMed

    Wadman, Renske I; Vrancken, Alexander F J E; van den Berg, Leonard H; van der Pol, W Ludo

    2012-11-13

    Spinal muscular atrophy (SMA) is pathologically characterized by degeneration of anterior horn cells. Recent observations in animal models of SMA and muscle tissue from patients with SMA suggest additional abnormalities in the development and maturation of the neuromuscular junction. We therefore evaluated neuromuscular junction function in SMA with repetitive nerve stimulation. In this case-control study, repetitive nerve stimulation was performed in 35 patients with SMA types 2, 3, and 4, 20 healthy controls, and 5 controls with motor neuron disease. Pathologic decremental responses (>10%) during 3-Hz repetitive nerve stimulation were observed in 17 of 35 patients (49%) with SMA types 2 and 3, but not in healthy controls or controls with motor neuron disease. None of the patients or controls had an abnormal incremental response of >60%. The presence of an abnormal decremental response was not specific for the type of SMA, nor was it associated with compound muscle action potential amplitude, clinical scores, or disease duration. Two of 4 patients with SMA type 3 who tried pyridostigmine reported increased stamina. These data suggest dysfunction of the neuromuscular junction in patients with SMA types 2 and 3. Therefore, drugs that facilitate neuromuscular transmission are candidate drugs for evaluation in carefully designed, placebo-controlled, clinical trials.

  8. Oxidative muscular injury and its relevance to hyperthyroidism.

    PubMed

    Asayama, K; Kato, K

    1990-01-01

    In experimental hyperthyroidism, acceleration of lipid peroxidation occurs in heart and slow-oxidative muscles, suggesting the contribution of reactive oxygen species to the muscular injury caused by thyroid hormones. This article reviews various models of oxidative muscular injury and considers the relevance of the accompanying metabolic derangements to thyrotoxic myopathy and cardiomyopathy, which are the major complications of hyperthyroidism. The muscular injury models in which reactive oxygen species are supposed to play a role are ischemia/reperfusion syndrome, exercise-induced myopathy, heart and skeletal muscle diseases related to the nutritional deficiency of selenium and vitamin E and related disorders, and genetic muscular dystrophies. These models provide evidence that mitochondrial function and the glutathione-dependent antioxidant system are important for the maintenance of the structural and functional integrity of muscular tissues. Thyroid hormones have a profound effect on mitochondrial oxidative activity, synthesis and degradation of proteins and vitamin E, the sensitivity of the tissues to catecholamine, the differentiation of muscle fibers, and the levels of antioxidant enzymes. The large volume of circumstantial evidence presented here indicates that hyperthyroid muscular tissues undergo several biochemical changes that predispose them to free radical-mediated injury.

  9. Genetic Modifiers of Duchenne and Facioscapulohumeral Muscular Dystrophies

    PubMed Central

    Hightower, Rylie M.; Alexander, Matthew S.

    2017-01-01

    Muscular dystrophy is defined as the progressive wasting of skeletal muscles that is caused by inherited or spontaneous genetic mutations. Next-generation sequencing (NGS) has greatly improved the accuracy and speed of diagnosis for different types of muscular dystrophy. Advancements in depth of coverage, convenience, and overall reduced cost, have led to the identification of genetic modifiers that are responsible for phenotypic variability in affected patients. These genetic modifiers have been postulated to explain key differences in disease phenotypes including age of loss of ambulation, steroid-responsiveness, and the presence or absence of cardiac defects in patients with the same form of muscular dystrophy. Here we review and highlight recent findings on genetic modifiers of Duchenne and Facioscapulohumeral muscular dystrophies based on animal and clinical studies. These genetic modifiers hold great promise to be developed into novel therapeutic targets for the treatment of muscular dystrophies. PMID:28877560

  10. Threatened masculinity and muscularity: an experimental examination of multiple aspects of muscularity in men.

    PubMed

    Hunt, Christopher John; Gonsalkorale, Karen; Murray, Stuart B

    2013-06-01

    Two studies examined the threatened masculinity theory of male body dissatisfaction, which posits that threats to masculinity result in increased muscle dissatisfaction. In Study 1, a masculinity threat was followed by tasks examining confidence in physical ability and perceptions of current and ideal body shapes. Results showed that men who experienced a masculinity threat reported lower confidence in their physical ability and perceived themselves as less muscular than men who experienced an affirmation of their masculinity. In Study 2, men were asked to report their intention to increase muscularity and their appearance anxiety following a threat to masculinity. Results showed that men reported lower appearance anxiety and drive for muscularity when their masculinity was threatened than when their masculinity was affirmed. This apparent contradiction can be explained by noting that men may be motivated to deny appearance concerns following a threat to masculinity, as such concerns are equated with femininity. Copyright © 2013. Published by Elsevier Ltd.

  11. BRANCHED FIBERS FROM OLD FAST-TWITCH DYSTROPHIC MUSCLES ARE THE SITES OF TERMINAL DAMAGE IN MUSCULAR DYSTROPHY.

    PubMed

    Kiriaev, Leonit; Kueh, Sindy; Morley, John W; North, Kathryn N; Houweling, Peter J; Head, Stewart I

    2018-02-07

    A striking pathological feature of dystrophinopathies is the presence of morphologically abnormal branched skeletal muscle fibers. The deterioration of muscle contractile function in Duchenne muscular dystrophy is accompanied by both an increase in number and complexity of these branched fibers. We propose that when number and complexity of branched fibers reaches a critical threshold, "tipping point" the branches in and of themselves are the site of contraction-induced rupture. In the present study, we use the dystrophic mdx mouse and littermate controls to study the pre-diseased dystrophic fast-twitch EDL muscle at 2-3-weeks, the peak myonecrotic phase at 6-9 weeks and finally "old" at 58-112 weeks. Using a combination of isolated muscle function contractile measurements coupled with single fiber imaging and confocal microscope imaging of cleared whole muscles we identified a distinct pathophysiology; acute fiber rupture at branch nodes, which occurs in "old" fast-twitch EDL muscle approaching the end stage of the dystrophinopathy muscle disease, where the EDL muscles are entirely composed of complexed branched fibers. This evidence supports our concept of "tipping point" where the number and extent of fiber branching reaches a level where the branching itself terminally compromises muscle function, irrespective of the absence of dystrophin.

  12. Association of recurrent pregnancy loss with chromosomal abnormalities and hereditary thrombophilias.

    PubMed

    Ocak, Z; Özlü, T; Ozyurt, O

    2013-06-01

    Recurrent pregnancy loss (RPL) which is generally known as >3 consecutive pregnancy losses before 20 weeks' gestation is seen in 0.5-2% of women. To evaluate the association of parental and fetal chromosomal abnormalities with recurrent pregnancy loss in our area and to analyze the frequency of three types of hereditary thrombophilia's; (MTHFR C677T polymorphisms, FV Leiden G1691A mutation and Prothrombin (factor II) G20210A mutation) in these female patients. The present case-control retrospective study was performed between February 2007 and December 2011 on 495 couples, who had two or more consecutive pregnancy losses before 20 weeks' gestation. We used conventional cytogenetic analysis and polymerase chain reaction-restriction fragment length polymorphism. Parental chromosomal abnormality was detected in 28 cases (2.8% of all cases, 5.7% of the couples) most of which (92.9%) were structural abnormalities. All of the structural abnormalities were balanced chromosomal translocations. Chromosomal analysis performed from the abortion materials detected a major chromosomal abnormality in 31.9% of the cases. The most frequently observed alteration in the hereditary thrombophilia genes was heterozygote mutation for the MTHFR C677T polymorphisms (n=55). Balanced translocations are the most commonly detected chromosomal abnormalities in couples being evaluated for recurrent pregnancy loss and these patients are the best candidates for offering prenatal genetic diagnosis by the help of which there is a possibility of obtaining a better reproductive outcome.

  13. 9 CFR 311.35 - Muscular inflammation, degeneration, or infiltration.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Muscular inflammation, degeneration, or infiltration. 311.35 Section 311.35 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE... PARTS § 311.35 Muscular inflammation, degeneration, or infiltration. (a) If muscular lesions are found...

  14. 9 CFR 311.35 - Muscular inflammation, degeneration, or infiltration.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Muscular inflammation, degeneration, or infiltration. 311.35 Section 311.35 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE... PARTS § 311.35 Muscular inflammation, degeneration, or infiltration. (a) If muscular lesions are found...

  15. 9 CFR 311.35 - Muscular inflammation, degeneration, or infiltration.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Muscular inflammation, degeneration, or infiltration. 311.35 Section 311.35 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE... PARTS § 311.35 Muscular inflammation, degeneration, or infiltration. (a) If muscular lesions are found...

  16. 9 CFR 311.35 - Muscular inflammation, degeneration, or infiltration.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Muscular inflammation, degeneration, or infiltration. 311.35 Section 311.35 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE... PARTS § 311.35 Muscular inflammation, degeneration, or infiltration. (a) If muscular lesions are found...

  17. 9 CFR 311.35 - Muscular inflammation, degeneration, or infiltration.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Muscular inflammation, degeneration, or infiltration. 311.35 Section 311.35 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE... PARTS § 311.35 Muscular inflammation, degeneration, or infiltration. (a) If muscular lesions are found...

  18. Muscular Subaortic Stenosis

    PubMed Central

    Wigle, E. Douglas; Auger, Pierre; Marquis, Yves

    1966-01-01

    Two types of intraventricular pressure differences within the left ventricle of man are described. The first is encountered in cases of muscular (or fibrous) subaortic stenosis, in which the outflow tract pressure distal to the stenosis (and proximal to the aortic valve) is low, whereas all pressures recorded in the left ventricle proximal to the stenosis, including that just inside the mitral valve (the initial inflow tract pressure) are high. The second type of intraventricular pressure difference may be recorded in patients without muscular subaortic stenosis when a heart catheter is advanced to the left ventricular wall in such a manner that it becomes imbedded or entrapped by cardiac muscle in systole. Such an entrapped catheter records a high intraventricular pressure that is believed to reflect intramyocardial tissue pressure, which normally exceeds intracavitary pressure. In such cases the initial inflow tract pressure is not high and is precisely equal to the outflow tract systolic pressure, i.e. both are recording intracavity pressure. This type of intramyocardial to intracavitary pressure difference may also be encountered in the left ventricle of dogs. The recent suggestion that intraventricular pressure differences in the left ventricle of cases of muscular subaortic stenosis are due to catheter entrapment by cardiac muscle is refuted by using the initial inflow tract pressure as the means of differentiation between the two types of intraventricular pressure differences outlined. PMID:5951625

  19. Genetic modifiers of Duchenne and facioscapulohumeral muscular dystrophies.

    PubMed

    Hightower, Rylie M; Alexander, Matthew S

    2018-01-01

    Muscular dystrophy is defined as the progressive wasting of skeletal muscles that is caused by inherited or spontaneous genetic mutations. Next-generation sequencing has greatly improved the accuracy and speed of diagnosis for different types of muscular dystrophy. Advancements in depth of coverage, convenience, and overall reduced cost have led to the identification of genetic modifiers that are responsible for phenotypic variability in affected patients. These genetic modifiers have been postulated to explain key differences in disease phenotypes, including age of loss of ambulation, steroid responsiveness, and the presence or absence of cardiac defects in patients with the same form of muscular dystrophy. This review highlights recent findings on genetic modifiers of Duchenne and facioscapulohumeral muscular dystrophies based on animal and clinical studies. These genetic modifiers hold great promise to be developed into novel therapeutic targets for the treatment of muscular dystrophies. Muscle Nerve 57: 6-15, 2018. © 2017 Wiley Periodicals, Inc.

  20. Changes in Muscle Metabolism are Associated with Phenotypic Variability in Golden Retriever Muscular Dystrophy




    PubMed Central

    Nghiem, Peter P.; Bello, Luca; Stoughton, William B.; López, Sara Mata; Vidal, Alexander H.; Hernandez, Briana V.; Hulbert, Katherine N.; Gourley, Taylor R.; Bettis, Amanda K.; Balog-Alvarez, Cynthia J.; Heath-Barnett, Heather; Kornegay, Joe N.

    2017-01-01

    Duchenne muscular dystrophy (DMD) is an X-chromosome-linked disorder and the most common monogenic disease in people. Affected boys are diagnosed at a young age, become non-ambulatory by their early teens, and succumb to cardiorespiratory failure by their thirties. Despite being a monogenic condition resulting from mutations in the DMD gene, affected boys have noteworthy phenotypic variability. Efforts have identified genetic modifiers that could modify disease progression and be pharmacologic targets. Dogs affected with golden retriever muscular dystrophy (GRMD) have absent dystrophin and demonstrate phenotypic variability at the functional, histopathological, and molecular level. Our laboratory is particularly interested in muscle metabolism changes in dystrophin-deficient muscle. We identified several metabolic alterations, including myofiber type switching from fast (type II) to slow (type I), reduced glycolytic enzyme expression, reduced and morphologically abnormal mitochondria, and differential AMP-kinase phosphorylation (activation) between hypertrophied and wasted muscle. We hypothesize that muscle metabolism changes are, in part, responsible for phenotypic variability in GRMD. Pharmacological therapies aimed at modulating muscle metabolism can be tested in GRMD dogs for efficacy. PMID:28955176

  1. Symptomatic muscular sarcoidosis: Lessons from a nationwide multicenter study.

    PubMed

    Cohen Aubart, Fleur; Abbara, Salam; Maisonobe, Thierry; Cottin, Vincent; Papo, Thomas; Haroche, Julien; Mathian, Alexis; Pha, Micheline; Gilardin, Laurent; Hervier, Baptiste; Soussan, Michael; Morlat, Philippe; Nunes, Hilario; Benveniste, Olivier; Amoura, Zahir; Valeyre, Dominique

    2018-05-01

    To describe clinicopathologic features of muscular sarcoidosis and the associated sarcoidosis phenotype through a nationwide multicenter study. Patients were included if they had histologically proven sarcoidosis and symptomatic muscular involvement confirmed by biological, imaging, or histologic examinations. Forty-eight patients (20 males) were studied, with a median age at muscular symptoms onset of 45 years (range 18-71). Four patterns were identified: a nodular pattern (27%); smoldering phenotype (29%); acute, subacute, or progressive myopathic type (35%); and combined myopathic and neurogenic pattern (10%). In all patterns, sarcoidosis was multivisceral with a median of 3 extramuscular organs involved (mostly lungs, lymph nodes, eyes, and skin) and a prolonged course with long-term use of corticosteroids and immunosuppressive drugs. Muscular patterns differed according to clinical presentation (myalgia, nodules, or weakness), electromyographic findings, muscular MRI, and response to sarcoidosis treatment. The myopathic and neuromuscular patterns were more severe. This nationwide study of muscular sarcoidosis allowed the identification of 4 patterns of granulomatous myositis, which differed by phenotypes and the clinical course.

  2. Pain in adolescents with spinal muscular atrophy and Duchenne and Becker muscular dystrophy.

    PubMed

    Lager, Christina; Kroksmark, Anna-Karin

    2015-09-01

    The purpose of this study was to explore the prevalence, nature and scope of pain in adolescents with spinal muscular atrophy and Duchenne and Becker muscular dystrophy and whether the pain differs between diagnostic groups or between adolescents with different ambulation status. Furthermore to study the consequences of pain and to identify pain-exacerbating and pain-relieving factors. In a national survey, fifty-five adolescents with spinal muscular atrophy and dystrophinopathy completed a questionnaire assessing pain frequency, duration, location using a body map, intensity and discomfort using visual analogue scales, pain interference using a modified version of Brief Pain Inventory and factors exacerbating and relieving pain. Sixty-nine per cent of the adolescents reported pain during the past three months and 50% reported chronic pain. The pain prevalence did not differ significantly between diagnostic groups or between ambulators and non-ambulators. The average pain intensity was graded as mild and the worst pain as moderate. The pain typically occurred weekly, most frequently in the neck/back or legs. General activity and mood were the areas that were most affected by pain. Common pain-exacerbating factors were sitting, too much movement/activity and being lifted or transferred. Pain is a frequent problem in adolescents with spinal muscular atrophy and dystrophinopathy. The assessments used enable an understanding both of the nature and scope of pain and of the impact of pain in everyday life. The study highlights the importance of assessing pain in a systematic manner and offering an individual approach to interventions designed to reduce pain in this population. Copyright © 2015 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  3. A comparison of swallowing dysfunction in Becker muscular dystrophy and Duchenne muscular dystrophy.

    PubMed

    Yamada, Yuka; Kawakami, Michiyuki; Wada, Ayako; Otsuka, Tomoyoshi; Muraoka, Kaori; Liu, Meigen

    2018-06-01

    Swallowing dysfunction has been reported in Duchenne muscular dystrophy (DMD), but has not been studied in Becker muscular dystrophy (BMD). The aims of this study were to report the characteristics of swallowing dysfunction in BMD compared with DMD. The study participants were 18 patients with BMD and 18 patients with DMD. All the patients were examined using videofluorography during swallowing of 5 mL of fluid. The penetration-aspiration scale (P-A scale) and the videofluorographic dysphagia scale (VDS) were used to evaluate dysphagia. Swinyard functional ability stage was not significantly different between the BMD and DMD groups. Rate of aspiration, P-A scale score, and total VDS score did not differ across groups, but the VDS item score for laryngeal elevation was lower in the BMD group than in the DMD group (median scores 4.5 and 9, respectively; p < 0.001). In the BMD group, total VDS score significantly correlated with Swinyard stage (r = 0.78, p < 0.001), but not with age or lung function. Patients with BMD have swallowing problems similar to those observed in patients with DMD when matched according to physical functional status. These patients should be evaluated and followed-up for the duration of their disease. Implications for rehabiliation Dysphagia is one of the most critical problems in patients with progressive neuromuscular disease but dysphagia in patients with Becker muscular dystrophy (BMD) was not well known. Eighteen patients with BMD and 18 patients with Duchenne muscular dystrophy were examined with videofluorography. Patients with BMD have swallowing problems similar to those observed in patients with DMD.

  4. AB033. Preimplantation genetic diagnosis of spinal muscular atrophy in Vietnam

    PubMed Central

    Khoa, Tran Van; Nga, Nguyen Thi Thanh; Tao, Nguyen Dinh; Sang, Trieu Tien; Giang, Ngo Truong; Dung, Vu Chi

    2015-01-01

    Objective Spinal muscular atrophy (SMA) is a severe neurodegenerative autosomal recessive disorder. Most of patients are caused by the homozygous absence of exon 7 of the telomeric copy of the SMN gene (SMNt) on chromosome 5. Setting up a molecular diagnostic protocol for detecting exon 7 gen SMNT homozygous deletion in single cell is basic to preimplantation genetic diagnosis of spinal muscular atrophy. Methods This study was carried out on 17 patients and their parents. Firstly, lymphocytes of patients and their parents were isolated from fresh blood by ficoll. Taking a lymphocyte on stereoscopic microscope, lysing the cell, amplifying whole genome, then amplifying exon 7 of SMNT gene by using a polymerase chain reaction, followed by HinfI restriction digest enzyme of the PCR enabling the important SMNT gene to be distinguished from the centromic SMN gene (SMNc) which has no clinical phenotype to detect mutation. Electrophoresis PCR products after digesting by restriction enzyme and analysis. Besides, the minisequencing technique has also been used to detect the absence of exon 7 of SMNT gene based on the difference of one nucleotide at 214-position in exon 7 (C-SMNT, T-SMNc). Secondly, the application of the protocol was set up on one lymphocyte to preimplantation genetic diagnosis of spinal muscular atrophy on biopsied blastomeres. Results Two different protocols which were PCR-RFLP and minisequencing, were set up on 200 lymphocytes from 17 patients and their parents to screen the homozygous deletion in exon 7 SMNT gene with the PCR efficiency in 96%. The results were similar with the gene diagnosed from fresh blood. The methods were also efficient, providing interpretable result in 96.55% (28/29) of the blastomeres tested. Three couples were treated using this method. Three normal embryos were transfer which resulted in one clinical pregnancy. Conclusions We have successfully applied the technique of PCR-RFLP and minisequencing for the preimplantation genetic

  5. Multi-body dynamic coupling mechanism for generating throwing arm velocity during baseball pitching.

    PubMed

    Naito, Kozo; Takagi, Tokio; Kubota, Hideaki; Maruyama, Takeo

    2017-08-01

    The purpose of this study was to identify the detailed mechanism how the maximum throwing arm endpoint velocity is determined by the muscular torques and non-muscular interactive torques from the perspective of the dynamic coupling among the trunk, thorax and throwing and non-throwing arm segments. The pitching movements of ten male collegiate baseball pitchers were measured by a three-dimensional motion capture system. Using the induced-segmental velocity analysis (IVA) developed in this study, the maximum fingertip velocity of the throwing arm (MFV) was decomposed into each contribution of the muscular torques, passive motion-dependent torques due to gyroscopic moment, Coriolis force and centrifugal force, and other interactive torque components. The results showed that MFV (31.6±1.7m/s) was mainly attributed to two different mechanisms. The first is the passive motion-dependent effect on increasing the angular velocities of three joints (thorax rotation, elbow extension and wrist flexion). The second is the muscular torque effect of the shoulder internal rotation (IR) torque on generating IR angular velocity. In particular, the centrifugal force-induced elbow extension motion, which was the greatest contributor among individual joint contributions, was caused primarily by the angular velocity-dependent forces associated with the humerus, thorax, and trunk rotations. Our study also found that a compensatory mechanism was achieved by the negative and positive contributions of the muscular torque components. The current IVA is helpful to understand how the rapid throwing arm movement is determined by the dynamic coupling mechanism. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Muscular contraction stimulates posterior hypothalamic neurons.

    PubMed

    Waldrop, T G; Stremel, R W

    1989-02-01

    Recent studies have suggested that the subthalamic locomotor region (STLR) of the posterior hypothalamus is involved in modulating cardiorespiratory responses to feedback from contracting muscles. The purpose of this study was to determine whether neurons in this hypothalamic region alter their discharge frequency during contraction of hindlimb muscles. Stainless steel electrodes were used to record single-unit activity of STLR neurons during static and rhythmic contractions of hindlimb muscles in anesthetized cats. Recordings were also made from neurons in areas outside but surrounding the subthalamic locomotor region. Contraction of the triceps surae muscles was induced by stimulation of the peripheral cut ends of the L7 and S1 ventral roots. Both static and rhythmic contractions of the triceps surae evoked an increase in the discharge rate of the majority of the STLR cells studied. Two types of excitatory responses were observed: 1) abrupt increases in discharge frequency at the onset of muscular contraction and 2) a delayed more gradual increase in firing. Most of the cells that responded to muscular contraction could be activated by mechanical probing of the triceps surae muscles. However, the changes in discharge frequency were unrelated to changes in arterial pressure occurring during muscular contraction. Most of the neurons located outside the STLR were slightly inhibited by or did not respond to muscular contraction. Thus input from contracting muscles exerts predominantly an excitatory effect on neurons in the posterior hypothalamus. These results are consistent with other studies which have concluded that this hypothalamic site is involved in influencing the cardiorespiratory responses to muscular contraction.

  7. Four-week rapamycin treatment improves muscular dystrophy in a fukutin-deficient mouse model of dystroglycanopathy.

    PubMed

    Foltz, Steven J; Luan, Junna; Call, Jarrod A; Patel, Ankit; Peissig, Kristen B; Fortunato, Marisa J; Beedle, Aaron M

    2016-01-01

    Secondary dystroglycanopathies are a subset of muscular dystrophy caused by abnormal glycosylation of α-dystroglycan (αDG). Loss of αDG functional glycosylation prevents it from binding to laminin and other extracellular matrix receptors, causing muscular dystrophy. Mutations in a number of genes, including FKTN (fukutin), disrupt αDG glycosylation. We analyzed conditional Fktn knockout (Fktn KO) muscle for levels of mTOR signaling pathway proteins by Western blot. Two cohorts of Myf5-cre/Fktn KO mice were treated with the mammalian target of rapamycin (mTOR) inhibitor rapamycin (RAPA) for 4 weeks and evaluated for changes in functional and histopathological features. Muscle from 17- to 25-week-old fukutin-deficient mice has activated mTOR signaling. However, in tamoxifen-inducible Fktn KO mice, factors related to Akt/mTOR signaling were unchanged before the onset of dystrophic pathology, suggesting that Akt/mTOR signaling pathway abnormalities occur after the onset of disease pathology and are not causative in early dystroglycanopathy development. To determine any pharmacological benefit of targeting mTOR signaling, we administered RAPA daily for 4 weeks to Myf5/Fktn KO mice to inhibit mTORC1. RAPA treatment reduced fibrosis, inflammation, activity-induced damage, and central nucleation, and increased muscle fiber size in Myf5/Fktn KO mice compared to controls. RAPA-treated KO mice also produced significantly higher torque at the conclusion of dosing. These findings validate a misregulation of mTOR signaling in dystrophic dystroglycanopathy skeletal muscle and suggest that such signaling molecules may be relevant targets to delay and/or reduce disease burden in dystrophic patients.

  8. Quantitative electromyography in ambulatory boys with Duchenne muscular dystrophy.

    PubMed

    Verma, Sumit; Lin, Jenny; Travers, Curtis; McCracken, Courtney; Shah, Durga

    2017-12-01

    This study's objective was to evaluate quantitative electromyography (QEMG) using multiple-motor-unit (multi-MUP) analysis in Duchenne muscular dystrophy (DMD). Ambulatory DMD boys, aged 5-15 years, were evaluated with QEMG at 6-month intervals over 14 months. EMG was performed in the right biceps brachii (BB) and tibialis anterior (TA) muscles. Normative QEMG data were obtained from age-matched healthy boys. Wilcoxon signed-rank tests were performed. Eighteen DMD subjects were enrolled, with a median age of 7 (interquartile range 7-10) years. Six-month evaluations were performed on 14 subjects. QEMG showed significantly abnormal mean MUP duration in BB and TA muscles, with no significant change over 6 months. QEMG is a sensitive electrophysiological marker of myopathy in DMD. Preliminary data do not reflect a significant change in MUP parameters over a 6-month interval; long-term follow-up QEMG studies are needed to understand its role as a biomarker for disease progression. Muscle Nerve 56: 1361-1364, 2017. © 2017 Wiley Periodicals, Inc.

  9. Phase 3 Study of Ataluren in Patients With Nonsense Mutation Duchenne Muscular Dystrophy

    ClinicalTrials.gov

    2017-12-11

    Muscular Dystrophy, Duchenne; Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn

  10. Nitric oxide deficiency determines global chromatin changes in Duchenne muscular dystrophy.

    PubMed

    Colussi, Claudia; Gurtner, Aymone; Rosati, Jessica; Illi, Barbara; Ragone, Gianluca; Piaggio, Giulia; Moggio, Maurizio; Lamperti, Costanza; D'Angelo, Grazia; Clementi, Emilio; Minetti, Giulia; Mozzetta, Chiara; Antonini, Annalisa; Capogrossi, Maurizio C; Puri, Pier Lorenzo; Gaetano, Carlo

    2009-07-01

    The present study provides evidence that abnormal patterns of global histone modification are present in the skeletal muscle nuclei of mdx mice and Duchenne muscular dystrophy (DMD) patients. A combination of specific histone H3 modifications, including Ser-10 phosphorylation, acetylation of Lys 9 and 14, and Lys 79 methylation, were found enriched in muscle biopsies from human patients affected by DMD and in late-term fetuses, early postnatal pups, or adult mdx mice. In this context, chromatin immunoprecipitation experiments showed an enrichment of these modifications at the loci of genes involved in proliferation or inflammation, suggesting a regulatory effect on gene expression. Remarkably, the reexpression of dystrophin induced by gentamicin treatment or the administration of nitric oxide (NO) donors reversed the abnormal pattern of H3 histone modifications. These findings suggest an unanticipated link between the dystrophin-activated NO signaling and the remodeling of chromatin. In this context, the regulation of class IIa histone deacetylases (HDACs) 4 and 5 was found altered as a consequence of the reduced NO-dependent protein phosphatase 2A activity, indicating that both NO and class IIa HDACs are important for satellite cell differentiation and gene expression in mdx mice. In conclusion, this work provides the first evidence of a role for NO as an epigenetic regulator in DMD.

  11. Contribution of Dysferlin Deficiency to Skeletal Muscle Pathology in Asymptomatic and Severe Dystroglycanopathy Models: Generation of a New Model for Fukuyama Congenital Muscular Dystrophy

    PubMed Central

    Kanagawa, Motoi; Lu, Zhongpeng; Ito, Chiyomi; Matsuda, Chie; Miyake, Katsuya; Toda, Tatsushi

    2014-01-01

    Defects in dystroglycan glycosylation are associated with a group of muscular dystrophies, termed dystroglycanopathies, that include Fukuyama congenital muscular dystrophy (FCMD). It is widely believed that abnormal glycosylation of dystroglycan leads to disease-causing membrane fragility. We previously generated knock-in mice carrying a founder retrotransposal insertion in fukutin, the gene responsible for FCMD, but these mice did not develop muscular dystrophy, which hindered exploring therapeutic strategies. We hypothesized that dysferlin functions may contribute to muscle cell viability in the knock-in mice; however, pathological interactions between glycosylation abnormalities and dysferlin defects remain unexplored. To investigate contributions of dysferlin deficiency to the pathology of dystroglycanopathy, we have crossed dysferlin-deficient dysferlin sjl/sjl mice to the fukutin-knock-in fukutin Hp/− and Large-deficient Large myd/myd mice, which are phenotypically distinct models of dystroglycanopathy. The fukutin Hp/− mice do not show a dystrophic phenotype; however, (dysferlin sjl/sjl: fukutin Hp/−) mice showed a deteriorated phenotype compared with (dysferlin sjl/sjl: fukutin Hp/+) mice. These data indicate that the absence of functional dysferlin in the asymptomatic fukutin Hp/− mice triggers disease manifestation and aggravates the dystrophic phenotype. A series of pathological analyses using double mutant mice for Large and dysferlin indicate that the protective effects of dysferlin appear diminished when the dystrophic pathology is severe and also may depend on the amount of dysferlin proteins. Together, our results show that dysferlin exerts protective effects on the fukutin Hp/− FCMD mouse model, and the (dysferlin sjl/sjl: fukutin Hp/−) mice will be useful as a novel model for a recently proposed antisense oligonucleotide therapy for FCMD. PMID:25198651

  12. Dystrophic changes in masticatory muscles related chewing problems and malocclusions in Duchenne muscular dystrophy.

    PubMed

    van den Engel-Hoek, L; de Groot, I J M; Sie, L T; van Bruggen, H W; de Groot, S A F; Erasmus, C E; van Alfen, N

    2016-06-01

    Dysphagia in Duchenne muscular dystrophy (DMD) worsens with age, with increasingly effortful mastication. The aims of this study were to describe mastication problems in consecutive stages in a group of patients with DMD and to determine related pathophysiological aspects of masticatory muscle structure, tongue thickness, bite force and dental characteristics. Data from 72 patients with DMD (4.3 to 28.0 years), divided into four clinical stages, were collected in a cross sectional study. Problems with mastication and the need for food adaptations, in combination with increased echogenicity of the masseter muscle, were already found in the early stages of the disease. A high percentage of open bites and cross bites were found, especially in the later stages. Tongue hypertrophy also increased over time. Increased dysfunction, reflected by increasingly abnormal echogenicity, of the masseter muscle and reduced occlusal contacts (anterior and posterior open bites) were mainly responsible for the hampered chewing. In all, this study shows the increasing involvement of various elements of the masticatory system in progressive Duchenne muscular dystrophy. To prevent choking and also nutritional deficiency, early detection of chewing problems by asking about feeding and mastication problems, as well as asking about food adaptations made, is essential and can lead to timely intervention. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Early-Onset LMNA-Associated Muscular Dystrophy with Later Involvement of Contracture.

    PubMed

    Lee, Younggun; Lee, Jung Hwan; Park, Hyung Jun; Choi, Young Chul

    2017-10-01

    The early diagnosis of LMNA-associated muscular dystrophy is important for preventing sudden arrest related to cardiac conduction block. However, diagnosing early-onset Emery-Dreifuss muscular dystrophy (EDMD) with later involvement of contracture and limb-girdle muscular dystrophy type 1B is often delayed due to heterogeneous clinical presentations. We aimed to determine the clinical features that contribute to a delayed diagnosis. We reviewed four patients who were recently diagnosed with LMNA-associated muscular dystrophy by targeted exome sequencing and who were initially diagnosed with nonspecific or other types of muscular dystrophy. Certain clinical features such as delayed contracture involvement and calf hypertrophy were found to contribute to a delayed diagnosis. Muscle biopsies were not informative for the diagnosis in these patients. Genetic testing of single or multiple genes is useful for confirming a diagnosis of LMNA-associated muscular dystrophy. Even EDMD patients could experience the later involvement of contracture, so clinicians should consider early genetic testing for patients with undiagnosed muscular dystrophy or laminopathy. Copyright © 2017 Korean Neurological Association

  14. Serum proteomic profiling reveals fragments of MYOM3 as potential biomarkers for monitoring the outcome of therapeutic interventions in muscular dystrophies

    PubMed Central

    Rouillon, Jérémy; Poupiot, Jérôme; Zocevic, Aleksandar; Amor, Fatima; Léger, Thibaut; Garcia, Camille; Camadro, Jean-Michel; Wong, Brenda; Pinilla, Robin; Cosette, Jérémie; Coenen-Stass, Anna M.L.; Mcclorey, Graham; Roberts, Thomas C.; Wood, Matthew J.A.; Servais, Laurent; Udd, Bjarne; Voit, Thomas; Richard, Isabelle; Svinartchouk, Fedor

    2015-01-01

    Therapy-responsive biomarkers are an important and unmet need in the muscular dystrophy field where new treatments are currently in clinical trials. By using a comprehensive high-resolution mass spectrometry approach and western blot validation, we found that two fragments of the myofibrillar structural protein myomesin-3 (MYOM3) are abnormally present in sera of Duchenne muscular dystrophy (DMD) patients, limb-girdle muscular dystrophy type 2D (LGMD2D) and their respective animal models. Levels of MYOM3 fragments were assayed in therapeutic model systems: (1) restoration of dystrophin expression by antisense oligonucleotide-mediated exon-skipping in mdx mice and (2) stable restoration of α-sarcoglycan expression in KO-SGCA mice by systemic injection of a viral vector. Following administration of the therapeutic agents MYOM3 was restored toward wild-type levels. In the LGMD model, where different doses of vector were used, MYOM3 restoration was dose-dependent. MYOM3 fragments showed lower inter-individual variability compared with the commonly used creatine kinase assay, and correlated better with the restoration of the dystrophin-associated protein complex and muscle force. These data suggest that the MYOM3 fragments hold promise for minimally invasive assessment of experimental therapies for DMD and other neuromuscular disorders. PMID:26060189

  15. [Supplementary device for a dynamometer to evaluate and register muscular endurance indices].

    PubMed

    Timoshenko, D A; Bokser, O Ia

    1986-01-01

    In practice of psychophysiologic research muscular endurance index is used for estimation of CNS function. Muscular endurance index is defined as relative time needed for maintaining the preset muscular effort. The described device widens the possibilities of a digital dynamometer for automatic estimation and recording of muscular endurance index in real time.

  16. Fatigue Effect on Low-Frequency Force Fluctuations and Muscular Oscillations during Rhythmic Isometric Contraction

    PubMed Central

    Lin, Yen-Ting; Kuo, Chia-Hua; Hwang, Ing-Shiou

    2014-01-01

    Continuous force output containing numerous intermittent force pulses is not completely smooth. By characterizing force fluctuation properties and force pulse metrics, this study investigated adaptive changes in trajectory control, both force-generating capacity and force fluctuations, as fatigue progresses. Sixteen healthy subjects (20–24 years old) completed rhythmic isometric gripping with the non-dominant hand to volitional failure. Before and immediately following the fatigue intervention, we measured the gripping force to couple a 0.5 Hz sinusoidal target in the range of 50–100% maximal voluntary contraction. Dynamic force output was off-line decomposed into 1) an ideal force trajectory spectrally identical to the target rate; and 2) a force pulse trace pertaining to force fluctuations and error-correction attempts. The amplitude of ideal force trajectory regarding to force-generating capacity was more suppressed than that of the force pulse trace with increasing fatigue, which also shifted the force pulse trace to lower frequency bands. Multi-scale entropy analysis revealed that the complexity of the force pulse trace at high time scales increased with fatigue, contrary to the decrease in complexity of the force pulse trace at low time scales. Statistical properties of individual force pulses in the spatial and temporal domains varied with muscular fatigue, concurrent with marked suppression of gamma muscular oscillations (40–60 Hz) in the post-fatigue test. In conclusion, this study first reveals that muscular fatigue impairs the amplitude modulation of force pattern generation more than it affects the amplitude responsiveness of fine-tuning a force trajectory. Besides, motor fatigue results disadvantageously in enhancement of motor noises, simplification of short-term force-tuning strategy, and slow responsiveness to force errors, pertaining to dimensional changes in force fluctuations, scaling properties of force pulse, and muscular oscillation

  17. Rare Muscular Dystrophies: Congenital, Distal, Emery-Dreifuss and Oculopharyngeal Muscular Dystrophies

    MedlinePlus

    ... although EDMD and OPMD can have more than one genetic cause). In most cases of muscular dystrophy, muscle mass in the affected ... categories. Many of these diseases can vary from one person to the next, and in some cases, research- ers are still in the process of ...

  18. Limb-girdle muscular dystrophies

    MedlinePlus

    ... diseases in which there is muscle weakness and wasting (muscular dystrophy). In most cases, both parents must ... which are not actually strong Loss of muscle mass, thinning of certain body parts Low back pain ...

  19. Limb-girdle muscular dystrophy subtypes: First-reported cohort from northeastern China

    PubMed Central

    Mahmood, Omar Abdulmonem; Jiang, Xinmei; Zhang, Qi

    2013-01-01

    The relative frequencies of different subtypes of limb-girdle muscular dystrophies vary widely among different populations. We estimated the percentage of limb-girdle muscular dystrophy subtypes in Chinese people based on 68 patients with limb-girdle muscular dystrophy from the Myology Clinic, Neurology Department, First Hospital of Jilin University, China. A diagnosis of calpainopathy was made in 12 cases (17%), and dysferlin deficiency in 10 cases (15%). Two biopsies revealed α-sarcoglycan deficiency (3%), and two others revealed a lack of caveolin-3 (3%). A diagnosis of unclassified limb-girdle muscular dystrophy was made in the remaining patients (62%). The appearances of calpain 3- and dysferlin-deficient biopsies were similar, though rimmed vacuoles were unique to dysferlinopathy, while inflammatory infiltrates were present in both these limb-girdle muscular dystrophy type 2D biopsies. Macrophages were detected in seven dysferlinopathy biopsies. The results of this study suggest that the distribution of limb-girdle muscular dystrophy subtypes in the Han Chinese population is similar to that reported in the West. The less necrotic, regenerating and inflammatory appearance of limb-girdle muscular dystrophy type 2A, but with more lobulated fibers, supports the idea that calpainopathy is a less active, but more chronic disease than dysferlinopathy. Unusual features indicated an extended limb-girdle muscular dystrophy disease spectrum. The use of acid phosphatase stain should be considered in suspected dysferlinopathies. To the best of our knowledge, this is the first report to define the relative proportions of the various forms of limb-girdle muscular dystrophy in China, based on protein testing. PMID:25206500

  20. Automated analysis of whole skeletal muscle for muscular atrophy detection of ALS in whole-body CT images: preliminary study

    NASA Astrophysics Data System (ADS)

    Kamiya, Naoki; Ieda, Kosuke; Zhou, Xiangrong; Yamada, Megumi; Kato, Hiroki; Muramatsu, Chisako; Hara, Takeshi; Miyoshi, Toshiharu; Inuzuka, Takashi; Matsuo, Masayuki; Fujita, Hiroshi

    2017-03-01

    Amyotrophic lateral sclerosis (ALS) causes functional disorders such as difficulty in breathing and swallowing through the atrophy of voluntary muscles. ALS in its early stages is difficult to diagnose because of the difficulty in differentiating it from other muscular diseases. In addition, image inspection methods for aggressive diagnosis for ALS have not yet been established. The purpose of this study is to develop an automatic analysis system of the whole skeletal muscle to support the early differential diagnosis of ALS using whole-body CT images. In this study, the muscular atrophy parts including ALS patients are automatically identified by recognizing and segmenting whole skeletal muscle in the preliminary steps. First, the skeleton is identified by its gray value information. Second, the initial area of the body cavity is recognized by the deformation of the thoracic cavity based on the anatomical segmented skeleton. Third, the abdominal cavity boundary is recognized using ABM for precisely recognizing the body cavity. The body cavity is precisely recognized by non-rigid registration method based on the reference points of the abdominal cavity boundary. Fourth, the whole skeletal muscle is recognized by excluding the skeleton, the body cavity, and the subcutaneous fat. Additionally, the areas of muscular atrophy including ALS patients are automatically identified by comparison of the muscle mass. The experiments were carried out for ten cases with abnormality in the skeletal muscle. Global recognition and segmentation of the whole skeletal muscle were well realized in eight cases. Moreover, the areas of muscular atrophy including ALS patients were well identified in the lower limbs. As a result, this study indicated the basic technology to detect the muscle atrophy including ALS. In the future, it will be necessary to consider methods to differentiate other kinds of muscular atrophy as well as the clinical application of this detection method for early ALS

  1. Delayed Diagnosis in Duchenne Muscular Dystrophy: Data from the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet)

    PubMed Central

    Ciafaloni, Emma; Fox, Deborah J.; Pandya, Shree; Westfield, Christina P.; Puzhankara, Soman; Romitti, Paul A.; Mathews, Katherine D.; Miller, Timothy M.; Matthews, Dennis J.; Miller, Lisa A.; Cunniff, Christopher; Druschel, Charlotte M.; Moxley, Richard T.

    2018-01-01

    Objective To identify key factors for the delay in diagnosis of Duchenne muscular dystrophy (DMD) without known family history. Study design The cohort comes from the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet), a multistate, multiple-source, population-based surveillance system that identifies and gathers information on all cases of Duchenne and Becker muscular dystrophy born since 1982. We analyzed medical records of 453 Duchenne and Becker muscular dystrophy boys to document the time course and steps taken to reach a definitive diagnosis. Results Among 156 boys without known family history of DMD prior to birth, first signs or symptoms were noted at a mean age of 2.5 years. Concerns resulted in primary care provider evaluation of the child at a mean age of 3.6 years. Mean age at time of initial creatine kinase was 4.7 years. Mean age at definitive diagnosis of DMD was 4.9 years. Conclusions There is a delay of about 2.5 years between onset of DMD symptoms and the time of definitive diagnosis, unchanged over the previous 2 decades. This delay results in lost opportunities for timely genetic counseling and initiation of corticosteroid treatment. We recommend checking creatine kinase early in the evaluation of boys with unexplained developmental delay. PMID:19394035

  2. Muscle Dysmorphia and the Perception of Men's Peer Muscularity Preferences.

    PubMed

    Lin, Linda; DeCusati, Frank

    2016-11-01

    Research suggests that peer muscularity norms preferences are related to men's body image, but little information is known about how perceptions of specific peer group norms preferences are related to men's body image disturbances and specific health behaviors. This study investigated how men perceived the muscularity preferences of male, female, close, and distant peers and whether the perceptions of specific peer preferences were related to muscle dysmorphia and steroid use. Data on muscle dysmorphia and the perceptions of peer muscularity norms were collected from 117 male college students. Results indicated that men perceived distant and male peers as having the most exaggerated preferences for muscularity and that those perceptions were not an accurate reflection of their distant male peers' reported preferences. Results also indicated that perceptions of close female peer muscularity preferences were predictive of symptoms of muscle dysmorphia, but this relationship did not exist for other peer groups, suggesting that the perceptions of close female peer preferences may play a role in the development of muscle dysmorphia. No relationship was found between perceptions of peer muscularity preferences and steroid use. © The Author(s) 2015.

  3. Who should be screened for chromosomal abnormalities before ICSI treatment?

    PubMed

    Dul, E C; van Ravenswaaij-Arts, C M A; Groen, H; van Echten-Arends, J; Land, J A

    2010-11-01

    Guidelines on karyotyping infertile men before ICSI treatment are not consistent. Most guidelines recommend chromosomal screening in azoospermic and severe oligozoospermic men, because they are assumed to have the highest risk of abnormalities. We performed a retrospective cohort study in azoospermic men and men eligible for ICSI. We determined the prevalence of chromosomal abnormalities in relation to sperm concentration and compared our data to studies in the literature. A high prevalence of chromosomal abnormalities in azoospermic men was found, but no difference in the prevalence of abnormalities was seen between different sperm concentration categories in non-azoospermic men. This raises the question of who should be screened for chromosomal abnormalities before ICSI treatment. Considering the costs and benefits, we would propose limiting screening to infertile couples with non-obstructive azoospermia.

  4. [INDIVIDUAL EVALUATION OF LORETA ABNORMALITIES IN IDIOPATHIC GENERALIZED EPILEPSY].

    PubMed

    Clemens, Béla; Puskás, Szilvia; Besenyei, Mónika; Kondákor, István; Hollódy, Katalin; Fogarasi, Andrós; Bense, Katalin; Emri, Miklós; Opposits Gábor; Kovács, Noémi Zsuzsanna; Fekete, István

    2016-03-30

    Contemporary neuroimaging methods disclosed structural and functional cerebral abnormalities in idiopathic generalized epilepsies (IGEs). However, individual electrical (EEG) abnormalities have not been evaluated yet in IGE patients. IGE patients were investigated in the drug-free condition and after 3-6 month of antiepileptic treatment. To estimate the reproducibility of qEEG variables a retrospective recruited cohort of IGE patients was investigated. 19-channel resting state EEG activity was recorded. For each patient a total of 2 minutes EEG activity was analyzed by LORETA (Low Resolution Electromagnetic Tomography). Raw LORETA values were Z-transformed and projected to a MRI template. Z-values outside within the [+3Z] to [-3Z] range were labelled as statistically abnormal. 1. In drug-free condition, 41-50% of IGE patients showed abnormal LORETA values. 2. Abnormal LORETA findings showed great inter-individual variability. 3. Most abnormal LORETA-findings were symmetrical. 4. Most maximum Z-values were localized to frontal or temporal cortex. 5. Succesfull treatment was mostly coupled with disappearence of LORETA-abnormality, persistent seizures were accompanied by persistent LORETA abnormality. 1. LORETA abnormalities detected in the untreated condition reflect seizure-generating property of the cortex in IGE patients. 2. Maximum LORETA-Z abnormalities were topographically congruent with structural abnormalities reported by other research groups. 3. LORETA might help to investigate drug effects at the whole-brain level.

  5. What is muscular dystrophy? Forty years of progressive ignorance.

    PubMed

    Dubowitz, V

    2000-01-01

    This lecture traces recent advances in knowledge of the muscular dystrophies, as well as their increasing complexity. They are described through the eyes of the author from his first exposure to and complete ignorance of the disease in the late 1950s, through the advent of modern techniques, to the molecular genetic revolution, with the recognition of individual genes and proteins for disorders within the muscular dystrophy umbrella. There initially seemed to be a logical sequence of linked membrane proteins from dystrophin in Duchenne and Becker dystrophy, through the dystrophin-associated glycoproteins (sarcoglycans) in some of the limb girdle muscular dystrophies (LGMD), to the extracellular matrix protein merosin (alpha-2 laminin) in congenital muscular dystrophy (CMD). The first spoke in the wheel came with the discovery of a calcium activated protease enzyme, calpain 3, in one form of LGMD, and subsequently another novel non-membrane protein, dysferlin, in another. There are currently at least eight distinct genetic forms of LGMD alone, and another eight separate genetic entities in the CMD group. This has highlighted our ignorance of the pathogenesis of the muscular dystrophies in relation to a diverse array of protein deficiencies. To compound things further, the X-linked and dominant forms of Emery-Dreifuss muscular dystrophy have recently been linked to emerin and lamin A/C, respectively, two proteins of the nuclear membrane, opening up yet another new ballpark of discovery.

  6. Why is muscularity sexy? Tests of the fitness indicator hypothesis.

    PubMed

    Frederick, David A; Haselton, Martie G

    2007-08-01

    Evolutionary scientists propose that exaggerated secondary sexual characteristics are cues of genes that increase offspring viability or reproductive success. In six studies the hypothesis that muscularity is one such cue is tested. As predicted, women rate muscular men as sexier, more physically dominant and volatile, and less committed to their mates than nonmuscular men. Consistent with the inverted-U hypothesis of masculine traits, men with moderate muscularity are rated most attractive. Consistent with past research on fitness cues, across two measures, women indicate that their most recent short-term sex partners were more muscular than their other sex partners (ds = .36, .47). Across three studies, when controlling for other characteristics (e.g., body fat), muscular men rate their bodies as sexier to women (partial rs = .49-.62) and report more lifetime sex partners (partial rs = .20-.27), short-term partners (partial rs = .25-.28), and more affairs with mated women (partial r = .28).

  7. Facioscapulohumeral Muscular Dystrophy.

    PubMed

    DeSimone, Alec M; Pakula, Anna; Lek, Angela; Emerson, Charles P

    2017-09-12

    Facioscapulohumeral Muscular Dystrophy is a common form of muscular dystrophy that presents clinically with progressive weakness of the facial, scapular, and humeral muscles, with later involvement of the trunk and lower extremities. While typically inherited as autosomal dominant, facioscapulohumeral muscular dystrophy (FSHD) has a complex genetic and epigenetic etiology that has only recently been well described. The most prevalent form of the disease, FSHD1, is associated with the contraction of the D4Z4 microsatellite repeat array located on a permissive 4qA chromosome. D4Z4 contraction allows epigenetic derepression of the array, and possibly the surrounding 4q35 region, allowing misexpression of the toxic DUX4 transcription factor encoded within the terminal D4Z4 repeat in skeletal muscles. The less common form of the disease, FSHD2, results from haploinsufficiency of the SMCHD1 gene in individuals carrying a permissive 4qA allele, also leading to the derepression of DUX4, further supporting a central role for DUX4. How DUX4 misexpression contributes to FSHD muscle pathology is a major focus of current investigation. Misexpression of other genes at the 4q35 locus, including FRG1 and FAT1, and unlinked genes, such as SMCHD1, has also been implicated as disease modifiers, leading to several competing disease models. In this review, we describe recent advances in understanding the pathophysiology of FSHD, including the application of MRI as a research and diagnostic tool, the genetic and epigenetic disruptions associated with the disease, and the molecular basis of FSHD. We discuss how these advances are leading to the emergence of new approaches to enable development of FSHD therapeutics. © 2017 American Physiological Society. Compr Physiol 7:1229-1279, 2017. Copyright © 2017 John Wiley & Sons, Inc.

  8. Guidelines for the Perianesthesia Care of the Duchenne Muscular Dystrophy/Becker Muscular Dystrophy Patient.

    PubMed

    Alliod, Barbara A; Ash, Rebecca A

    2016-12-01

    More patients suffering with Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are presenting to perianesthesia settings for emergent and nonemergent treatment and care. A group of collaborative health care providers at Rush University Medical Center in Chicago developed a multidisciplinary DMD/BMD Task Force to study this disorder and create a set of guidelines to aid those engaging in the planning, execution of care, and recovery of this unique population in the perianesthesia setting. Attention to detail, well-executed preplanning, meticulous awareness of the patient, and prearranged implementation and intervention has proven to offset potential problems and complications and is the key to a successful perianesthesia period. Copyright © 2016 American Society of PeriAnesthesia Nurses. Published by Elsevier Inc. All rights reserved.

  9. Cardiac function in muscular dystrophy associates with abdominal muscle pathology.

    PubMed

    Gardner, Brandon B; Swaggart, Kayleigh A; Kim, Gene; Watson, Sydeaka; McNally, Elizabeth M

    The muscular dystrophies target muscle groups differentially. In mouse models of muscular dystrophy, notably the mdx model of Duchenne Muscular Dystrophy, the diaphragm muscle shows marked fibrosis and at an earlier age than other muscle groups, more reflective of the histopathology seen in human muscular dystrophy. Using a mouse model of limb girdle muscular dystrophy, the Sgcg mouse, we compared muscle pathology across different muscle groups and heart. A cohort of nearly 200 Sgcg mice were studied using multiple measures of pathology including echocardiography, Evans blue dye uptake and hydroxyproline content in multiple muscle groups. Spearman rank correlations were determined among echocardiographic and pathological parameters. The abdominal muscles were found to have more fibrosis than other muscle groups, including the diaphragm muscle. The abdominal muscles also had more Evans blue dye uptake than other muscle groups. The amount of diaphragm fibrosis was found to correlate positively with fibrosis in the left ventricle, and abdominal muscle fibrosis correlated with impaired left ventricular function. Fibrosis in the abdominal muscles negatively correlated with fibrosis in the diaphragm and right ventricles. Together these data reflect the recruitment of abdominal muscles as respiratory muscles in muscular dystrophy, a finding consistent with data from human patients.

  10. DUX4, a candidate gene for facioscapulohumeral muscular dystrophy, causes p53-dependent myopathy in vivo.

    PubMed

    Wallace, Lindsay M; Garwick, Sara E; Mei, Wenyan; Belayew, Alexandra; Coppee, Frederique; Ladner, Katherine J; Guttridge, Denis; Yang, Jing; Harper, Scott Q

    2011-03-01

    Facioscapulohumeral muscular dystrophy (FSHD) is associated with D4Z4 repeat contraction on human chromosome 4q35. This genetic lesion does not result in complete loss or mutation of any gene. Consequently, the pathogenic mechanisms underlying FSHD have been difficult to discern. In leading FSHD pathogenesis models, D4Z4 contractions are proposed to cause epigenetic changes, which ultimately increase expression of genes with myopathic potential. Although no gene has been conclusively linked to FSHD development, recent evidence supports a role for the D4Z4-encoded DUX4 gene in FSHD. In this study, our objective was to test the in vivo myopathic potential of DUX4. We delivered DUX4 to zebrafish and mouse muscle by transposon-mediated transgenesis and adeno-associated viral vectors, respectively. Overexpression of DUX4, which encodes a transcription factor, caused abnormalities associated with muscular dystrophy in zebrafish and mice. This toxicity required DNA binding, because a DUX4 DNA binding domain mutant produced no abnormalities. Importantly, we found the myopathic effects of DUX4 were p53 dependent, as p53 inhibition mitigated DUX4 toxicity in vitro, and muscles from p53 null mice were resistant to DUX4-induced damage. Our work demonstrates the myopathic potential of DUX4 in animal muscle. Considering previous studies showed DUX4 was elevated in FSHD patient muscles, our data support the hypothesis that DUX4 overexpression contributes to FSHD development. Moreover, we provide a p53-dependent mechanism for DUX4 toxicity that is consistent with previous studies showing p53 pathway activation in FSHD muscles. Our work justifies further investigation of DUX4 and the p53 pathway in FSHD pathogenesis. Copyright © 2010 American Neurological Association.

  11. DUX4, a Candidate Gene for Facioscapulohumeral Muscular Dystrophy, Causes p53-Dependent Myopathy In Vivo

    PubMed Central

    Wallace, Lindsay M.; Garwick, Sara E.; Mei, Wenyan; Belayew, Alexandra; Coppee, Frederique; Ladner, Katherine J.; Guttridge, Denis; Yang, Jing; Harper, Scott Q.

    2014-01-01

    Objective Facioscapulohumeral muscular dystrophy (FSHD) is associated with D4Z4 repeat contraction on human chromosome 4q35. This genetic lesion does not result in complete loss or mutation of any gene. Consequently, the pathogenic mechanisms underlying FSHD have been difficult to discern. In leading FSHD pathogenesis models, D4Z4 contractions are proposed to cause epigenetic changes, which ultimately increase expression of genes with myopathic potential. Although no gene has been conclusively linked to FSHD development, recent evidence supports a role for the D4Z4-encoded DUX4 gene in FSHD. In this study, our objective was to test the in vivo myopathic potential of DUX4. Methods We delivered DUX4 to zebrafish and mouse muscle by transposon-mediated transgenesis and adeno-associated viral vectors, respectively. Results Overexpression of DUX4, which encodes a transcription factor, caused abnormalities associated with muscular dystrophy in zebrafish and mice. This toxicity required DNA binding, because a DUX4 DNA binding domain mutant produced no abnormalities. Importantly, we found the myopathic effects of DUX4 were p53 dependent, as p53 inhibition mitigated DUX4 toxicity in vitro, and muscles from p53 null mice were resistant to DUX4-induced damage. Interpretation Our work demonstrates the myopathic potential of DUX4 in animal muscle. Considering previous studies showed DUX4 was elevated in FSHD patient muscles, our data support the hypothesis that DUX4 overexpression contributes to FSHD development. Moreover, we provide a p53-dependent mechanism for DUX4 toxicity that is consistent with previous studies showing p53 pathway activation in FSHD muscles. Our work justifies further investigation of DUX4 and the p53 pathway in FSHD pathogenesis. PMID:21446026

  12. Genetic counseling for men with recurrent pregnancy loss or recurrent implantation failure due to abnormal sperm chromosomal aneuploidy.

    PubMed

    Kohn, Taylor P; Kohn, Jaden R; Darilek, Sandra; Ramasamy, Ranjith; Lipshultz, Larry

    2016-05-01

    The purpose of this study is to review recurrent pregnancy loss (RPL) due to sperm chromosomal abnormalities and discuss the genetic counseling that is required for men with sperm chromosomal abnormalities. The literature was reviewed, and a genetic counselor lends her expertise as to how couples with RPL and sperm chromosomal abnormalities ought to be counseled. The review of the literature was performed using MEDLINE. Sperm fluorescence in situ hybridization (FISH) can be used to determine if disomy or unbalanced chromosomal translocations are present. In men with aneuploidy in sperm or who carry a chromosomal translocation, pre-implantation genetic screening (PGS) combined with in vitro fertilization (IVF) and intra-cytoplasmic sperm injection (ICSI) can increase chances of live birth. In men with abnormal sperm FISH results, the degree of increased risk of abnormal pregnancy remains unclear. Genetic counselors can provide information to couples about the risk for potential trisomies and sex chromosome aneuploidies and discuss their reproductive and testing options such as PGS, use of donor sperm, and adoption. The provision of genetic counseling also allows a couple to be educated about recommended prenatal testing since pregnancies conceived with a partner who has had abnormal sperm FISH are considered to be at increased risk for aneuploidy. We review the literature and discuss genetic counseling for couples with RPL or recurrent implantation failure due to increased sperm aneuploidy.

  13. A Study of CAP-1002 in Ambulatory and Non-Ambulatory Patients With Duchenne Muscular Dystrophy

    ClinicalTrials.gov

    2018-06-16

    Muscular Dystrophies; Muscular Dystrophy, Duchenne; Muscular Disorders, Atrophic; Muscular Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn

  14. Inhibition of Prostaglandin D Synthase Suppresses Muscular Necrosis

    PubMed Central

    Mohri, Ikuko; Aritake, Kosuke; Taniguchi, Hidetoshi; Sato, Yo; Kamauchi, Shinya; Nagata, Nanae; Maruyama, Toshihiko; Taniike, Masako; Urade, Yoshihiro

    2009-01-01

    Duchenne muscular dystrophy is a fatal muscle wasting disease that is characterized by a deficiency in the protein dystrophin. Previously, we reported that the expression of hematopoietic prostaglandin D synthase (HPGDS) appeared in necrotic muscle fibers from patients with either Duchenne muscular dystrophy or polymyositis. HPGDS is responsible for the production of the inflammatory mediator, prostaglandin D2. In this paper, we validated the hypothesis that HPGDS has a role in the etiology of muscular necrosis. We investigated the expression of HPGDS/ prostaglandin D2 signaling using two different mouse models of muscle necrosis, that is, bupivacaine-induced muscle necrosis and the mdx mouse, which has a genetic muscular dystrophy. We treated each mouse model with the HPGDS-specific inhibitor, HQL-79, and measured both necrotic muscle volume and selected cytokine mRNA levels. We confirmed that HPGDS expression was induced in necrotic muscle fibers in both bupivacaine-injected muscle and mdx mice. After administration of HQL-79, necrotic muscle volume was significantly decreased in both mouse models. Additionally, mRNA levels of both CD11b and transforming growth factor β1 were significantly lower in HQL-79-treated mdx mice than in vehicle-treated animals. We also demonstrated that HQL-79 suppressed prostaglandin D2 production and improved muscle strength in the mdx mouse. Our results show that HPGDS augments inflammation, which is followed by muscle injury. Furthermore, the inhibition of HPGDS ameliorates muscle necrosis even in cases of genetic muscular dystrophy. PMID:19359520

  15. Abnormal splicing switch of DMD's penultimate exon compromises muscle fibre maintenance in myotonic dystrophy.

    PubMed

    Rau, Frédérique; Lainé, Jeanne; Ramanoudjame, Laetitita; Ferry, Arnaud; Arandel, Ludovic; Delalande, Olivier; Jollet, Arnaud; Dingli, Florent; Lee, Kuang-Yung; Peccate, Cécile; Lorain, Stéphanie; Kabashi, Edor; Athanasopoulos, Takis; Koo, Taeyoung; Loew, Damarys; Swanson, Maurice S; Le Rumeur, Elisabeth; Dickson, George; Allamand, Valérie; Marie, Joëlle; Furling, Denis

    2015-05-28

    Myotonic Dystrophy type 1 (DM1) is a dominant neuromuscular disease caused by nuclear-retained RNAs containing expanded CUG repeats. These toxic RNAs alter the activities of RNA splicing factors resulting in alternative splicing misregulation and muscular dysfunction. Here we show that the abnormal splicing of DMD exon 78 found in dystrophic muscles of DM1 patients is due to the functional loss of MBNL1 and leads to the re-expression of an embryonic dystrophin in place of the adult isoform. Forced expression of embryonic dystrophin in zebrafish using an exon-skipping approach severely impairs the mobility and muscle architecture. Moreover, reproducing Dmd exon 78 missplicing switch in mice induces muscle fibre remodelling and ultrastructural abnormalities including ringed fibres, sarcoplasmic masses or Z-band disorganization, which are characteristic features of dystrophic DM1 skeletal muscles. Thus, we propose that splicing misregulation of DMD exon 78 compromises muscle fibre maintenance and contributes to the progressive dystrophic process in DM1.

  16. Abnormal splicing switch of DMD's penultimate exon compromises muscle fibre maintenance in myotonic dystrophy

    PubMed Central

    Rau, Frédérique; Lainé, Jeanne; Ramanoudjame, Laetitita; Ferry, Arnaud; Arandel, Ludovic; Delalande, Olivier; Jollet, Arnaud; Dingli, Florent; Lee, Kuang-Yung; Peccate, Cécile; Lorain, Stéphanie; Kabashi, Edor; Athanasopoulos, Takis; Koo, Taeyoung; Loew, Damarys; Swanson, Maurice S.; Le Rumeur, Elisabeth; Dickson, George; Allamand, Valérie; Marie, Joëlle; Furling, Denis

    2015-01-01

    Myotonic Dystrophy type 1 (DM1) is a dominant neuromuscular disease caused by nuclear-retained RNAs containing expanded CUG repeats. These toxic RNAs alter the activities of RNA splicing factors resulting in alternative splicing misregulation and muscular dysfunction. Here we show that the abnormal splicing of DMD exon 78 found in dystrophic muscles of DM1 patients is due to the functional loss of MBNL1 and leads to the re-expression of an embryonic dystrophin in place of the adult isoform. Forced expression of embryonic dystrophin in zebrafish using an exon-skipping approach severely impairs the mobility and muscle architecture. Moreover, reproducing Dmd exon 78 missplicing switch in mice induces muscle fibre remodelling and ultrastructural abnormalities including ringed fibres, sarcoplasmic masses or Z-band disorganization, which are characteristic features of dystrophic DM1 skeletal muscles. Thus, we propose that splicing misregulation of DMD exon 78 compromises muscle fibre maintenance and contributes to the progressive dystrophic process in DM1. PMID:26018658

  17. Cancer cachexia causes skeletal muscle damage via transient receptor potential vanilloid 2‐independent mechanisms, unlike muscular dystrophy

    PubMed Central

    Suzuki, Nobuyuki; Ohtake, Hitomi; Kamauchi, Shinya; Hashimoto, Naohiro; Kiyono, Tohru; Wakabayashi, Shigeo

    2015-01-01

    Abstract Background Muscle wasting during cancer cachexia contributes to patient morbidity. Cachexia‐induced muscle damage may be understood by comparing its symptoms with those of other skeletal muscle diseases, but currently available data are limited. Methods We modelled cancer cachexia in mice bearing Lewis lung carcinoma/colon adenocarcinoma and compared the associated muscle damage with that in a murine muscular dystrophy model (mdx mice). We measured biochemical and immunochemical parameters: amounts/localization of cytoskeletal proteins and/or Ca2+ signalling proteins related to muscle function and abnormality. We analysed intracellular Ca2+ mobilization and compared results between the two models. Involvement of Ca2+‐permeable channel transient receptor potential vanilloid 2 (TRPV2) was examined by inoculating Lewis lung carcinoma cells into transgenic mice expressing dominant‐negative TRPV2. Results Tumourigenesis caused loss of body and skeletal muscle weight and reduced muscle force and locomotor activity. Similar to mdx mice, cachexia muscles exhibited myolysis, reduced sarcolemmal sialic acid content, and enhanced lysosomal exocytosis and sarcolemmal localization of phosphorylated Ca2+/CaMKII. Abnormal autophagy and degradation of dystrophin also occurred. Unlike mdx muscles, cachexia muscles did not exhibit regeneration markers (centrally nucleated fibres), and levels of autophagic proteolytic pathway markers increased. While a slight accumulation of TRPV2 was observed in cachexia muscles, Ca2+ influx via TRPV2 was not elevated in cachexia‐associated myotubes, and the course of cachexia pathology was not ameliorated by dominant‐negative inhibition of TRPV2. Conclusions Thus, cancer cachexia may induce muscle damage through TRPV2‐independent mechanisms distinct from those in muscular dystrophy; this may help treat patients with tumour‐induced muscle wasting. PMID:27239414

  18. The relationship between muscularity, muscle:bone ratio and cut dimensions in male and female lamb carcasses and the measurement of muscularity using image analysis.

    PubMed

    Hopkins, D L

    1996-12-01

    Dorsal images of 57 whole lamb carcasses (mean 22.5 kg, SD 2.3 kg) were obtained on a slaughter chain using a video camera. The lambs represented two sexes (29 cryptorchids, 28 ewes) and one genotype (Poll Dorset × Border Leicester × Merino). Cryptorchid carcasses were significantly (P < 0.05) leaner than ewe carcasses at a common weight but there was little difference in dimensional measurements of M. longissimus thoracis et lumborum (LL). The cryptorchid carcasses had a significantly better conformation (based on the EUROP system) even when adjusted to the same carcass weight and subcutaneous fat level. From the hindleg and chump the following muscles were dissected and weighed: M. semimembranosus, M. adductor femoris, M. semitendinosus, M. biceps femoris, and M. quadriceps femoris. The femur was weighed, the length measured and a muscularity value calculated as described by Purchas et al. (1991 Meat Sci., 30, 181). There was no significant effect of sex on muscularity or muscle to bone ratio (M:B). Cryptorchid carcasses produced heavier (P < 0.05) round and midloin cuts but lighter (P < 0.05) chump and ribloin cuts. Overall there was no significant sex effect on the yield of hindquarter cuts. Correlation showed a significant (P < 0.001) association between LL area and muscularity, with a lower correlation between round and topside cross-sectional area and muscularity. Neither muscle cross-sectional area nor muscularity was significantly related to M:B ratios. Muscularity increased with increasing carcass weight (P < 0.001) but M:B did not. Prediction of muscularity was significantly (P < 0.05) improved by adding to hot carcass weight a measure of the combined width across the hind legs at interval three, as taken from video images, there being five equally-spaced intervals from the groin to the gambrel. A similar result was achieved by using carcass width at the third interval of five-eventy spaced intervals between the minimum shoulder width and the point of

  19. Dysphagia in Duchenne Muscular Dystrophy Assessed by Validated Questionnaire

    ERIC Educational Resources Information Center

    Archer, Sally K.; Garrod, Rachel; Hart, Nicholas; Miller, Simon

    2013-01-01

    Background: Duchenne muscular dystrophy (DMD) leads to progressive muscular weakness and death, most typically from respiratory complications. Dysphagia is common in DMD; however, the most appropriate swallowing assessments have not been universally agreed and the symptoms of dysphagia remain under-reported. Aims: To investigate symptoms of…

  20. Effects of systemic multiexon skipping with peptide-conjugated morpholinos in the heart of a dog model of Duchenne muscular dystrophy

    PubMed Central

    Echigoya, Yusuke; Nakamura, Akinori; Nagata, Tetsuya; Urasawa, Nobuyuki; Trieu, Nhu; Panesar, Dharminder; Kuraoka, Mutsuki; Moulton, Hong M.; Saito, Takashi; Aoki, Yoshitsugu; Iversen, Patrick; Sazani, Peter; Kole, Ryszard; Maruyama, Rika; Partridge, Terry; Takeda, Shin’ichi; Yokota, Toshifumi

    2017-01-01

    Duchenne muscular dystrophy (DMD) is a lethal genetic disorder caused by an absence of the dystrophin protein in bodywide muscles, including the heart. Cardiomyopathy is a leading cause of death in DMD. Exon skipping via synthetic phosphorodiamidate morpholino oligomers (PMOs) represents one of the most promising therapeutic options, yet PMOs have shown very little efficacy in cardiac muscle. To increase therapeutic potency in cardiac muscle, we tested a next-generation morpholino: arginine-rich, cell-penetrating peptide-conjugated PMOs (PPMOs) in the canine X-linked muscular dystrophy in Japan (CXMDJ) dog model of DMD. A PPMO cocktail designed to skip dystrophin exons 6 and 8 was injected intramuscularly, intracoronarily, or intravenously into CXMDJ dogs. Intravenous injections with PPMOs restored dystrophin expression in the myocardium and cardiac Purkinje fibers, as well as skeletal muscles. Vacuole degeneration of cardiac Purkinje fibers, as seen in DMD patients, was ameliorated in PPMO-treated dogs. Although symptoms and functions in skeletal muscle were not ameliorated by i.v. treatment, electrocardiogram abnormalities (increased Q-amplitude and Q/R ratio) were improved in CXMDJ dogs after intracoronary or i.v. administration. No obvious evidence of toxicity was found in blood tests throughout the monitoring period of one or four systemic treatments with the PPMO cocktail (12 mg/kg/injection). The present study reports the rescue of dystrophin expression and recovery of the conduction system in the heart of dystrophic dogs by PPMO-mediated multiexon skipping. We demonstrate that rescued dystrophin expression in the Purkinje fibers leads to the improvement/prevention of cardiac conduction abnormalities in the dystrophic heart. PMID:28373570

  1. Effects of systemic multiexon skipping with peptide-conjugated morpholinos in the heart of a dog model of Duchenne muscular dystrophy.

    PubMed

    Echigoya, Yusuke; Nakamura, Akinori; Nagata, Tetsuya; Urasawa, Nobuyuki; Lim, Kenji Rowel Q; Trieu, Nhu; Panesar, Dharminder; Kuraoka, Mutsuki; Moulton, Hong M; Saito, Takashi; Aoki, Yoshitsugu; Iversen, Patrick; Sazani, Peter; Kole, Ryszard; Maruyama, Rika; Partridge, Terry; Takeda, Shin'ichi; Yokota, Toshifumi

    2017-04-18

    Duchenne muscular dystrophy (DMD) is a lethal genetic disorder caused by an absence of the dystrophin protein in bodywide muscles, including the heart. Cardiomyopathy is a leading cause of death in DMD. Exon skipping via synthetic phosphorodiamidate morpholino oligomers (PMOs) represents one of the most promising therapeutic options, yet PMOs have shown very little efficacy in cardiac muscle. To increase therapeutic potency in cardiac muscle, we tested a next-generation morpholino: arginine-rich, cell-penetrating peptide-conjugated PMOs (PPMOs) in the canine X-linked muscular dystrophy in Japan (CXMD J ) dog model of DMD. A PPMO cocktail designed to skip dystrophin exons 6 and 8 was injected intramuscularly, intracoronarily, or intravenously into CXMD J dogs. Intravenous injections with PPMOs restored dystrophin expression in the myocardium and cardiac Purkinje fibers, as well as skeletal muscles. Vacuole degeneration of cardiac Purkinje fibers, as seen in DMD patients, was ameliorated in PPMO-treated dogs. Although symptoms and functions in skeletal muscle were not ameliorated by i.v. treatment, electrocardiogram abnormalities (increased Q-amplitude and Q/R ratio) were improved in CXMD J dogs after intracoronary or i.v. administration. No obvious evidence of toxicity was found in blood tests throughout the monitoring period of one or four systemic treatments with the PPMO cocktail (12 mg/kg/injection). The present study reports the rescue of dystrophin expression and recovery of the conduction system in the heart of dystrophic dogs by PPMO-mediated multiexon skipping. We demonstrate that rescued dystrophin expression in the Purkinje fibers leads to the improvement/prevention of cardiac conduction abnormalities in the dystrophic heart.

  2. Muscular and Aerobic Fitness, Working Memory, and Academic Achievement in Children.

    PubMed

    Kao, Shih-Chun; Westfall, Daniel R; Parks, Andrew C; Pontifex, Matthew B; Hillman, Charles H

    2017-03-01

    This study investigated the relationship between aerobic and muscular fitness with working memory and academic achievement in preadolescent children. Seventy-nine 9- to 11-yr-old children completed an aerobic fitness assessment using a graded exercise test; a muscular fitness assessment consisting of upper body, lower body, and core exercises; a serial n-back task to assess working memory; and an academic achievement test of mathematics and reading. Hierarchical regression analyses indicated that after controlling for demographic variables (age, sex, grade, IQ, socioeconomic status), aerobic fitness was associated with greater response accuracy and d' in the 2-back condition and increased mathematic performance in algebraic functions. Muscular fitness was associated with increased response accuracy and d', and longer reaction time in the 2-back condition. Further, the associations of muscular fitness with response accuracy and d' in the 2-back condition were independent of aerobic fitness. The current findings suggest the differential relationships between the aerobic and the muscular aspects of physical fitness with working memory and academic achievement. With the majority of research focusing on childhood health benefits of aerobic fitness, this study suggests the importance of muscular fitness to cognitive health during preadolescence.

  3. Genetics Home Reference: spinal muscular atrophy with progressive myoclonic epilepsy

    MedlinePlus

    ... myoclonic epilepsy Spinal muscular atrophy with progressive myoclonic epilepsy Printable PDF Open All Close All Enable Javascript ... boxes. Description Spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME) is a neurological condition that causes ...

  4. Intramuscular pressure and torque during isometric, concentric and eccentric muscular activity

    NASA Technical Reports Server (NTRS)

    Styf, J.; Ballard, R.; Aratow, M.; Crenshaw, A.; Watenpaugh, D.; Hargens, A. R.

    1995-01-01

    Intramuscular pressures, electromyography (EMG) and torque generation during isometric, concentric and eccentric maximal isokinetic muscle activity were recorded in 10 healthy volunteers. Pressure and EMG activity were continuously and simultaneously measured side by side in the tibialis anterior and soleus muscles. Ankle joint torque and position were monitored continuously by an isokinetic dynamometer during plantar flexion and dorsiflexion of the foot. The increased force generation during eccentric muscular activity, compared with other muscular activity, was not accompanied by higher intramuscular pressure. Thus, this study demonstrated that eccentric muscular activity generated higher torque values for each increment of intramuscular pressure. Intramuscular pressures during antagonistic co-activation were significantly higher in the tibilis anterior muscle (42-46% of maximal agonistic activity) compared with the soleus muscle (12-29% of maximal agonistic activity) and was largely due to active recruitment of muscle fibers. In summary, eccentric muscular activity creates higher torque values with no additional increase of the intramuscular pressure compared with concentric and isometric muscular activity.

  5. The Impact of Obesity on Back and Core Muscular Endurance in Firefighters

    PubMed Central

    Mayer, John M.; Nuzzo, James L.; Chen, Ren; Quillen, William S.; Verna, Joe L.; Miro, Rebecca; Dagenais, Simon

    2012-01-01

    The purpose of this study was to assess the relationships between obesity and measures of back and core muscular endurance in firefighters. Methods. A cross-sectional study was conducted in career firefighters without low back pain. Obesity measures included body mass index (BMI) and body fat percentage assessed with air displacement plethysmography. Muscular endurance was assessed with the Modified Biering Sorensen (back) and Plank (core) tests. Relationships were explored using t-tests and regression analyses. Results. Of the 83 participants enrolled, 24 (29%) were obese (BMI ≥ 30). Back and core muscular endurance was 27% lower for obese participants. Significant negative correlations were observed for BMI and body fat percentage with back and core endurance (r = −0.42 to −0.52). Stepwise regression models including one obesity measure (BMI, body fat percentage, and fat mass/fat-free mass), along with age and self-reported physical exercise, accounted for 17–19% of the variance in back muscular endurance and 29–37% of the variance in core muscular endurance. Conclusions. Obesity is associated with reduced back and core muscular endurance in firefighters, which may increase the risk of musculoskeletal injuries. Obesity should be considered along with back and core muscular endurance when designing exercise programs for back pain prevention in firefighters. PMID:23213491

  6. Meaning of Muscular Dystrophy

    MedlinePlus

    ... is very similar to Duchenne, except kids with Becker MD may not have problems until much later, when they're teenagers or adults. It takes a long time for their muscles to become weak. How Does a Kid Get Muscular Dystrophy? MD is not contagious (say: con-TAY-juss), ...

  7. Muscular activity and its relationship to biomechanics and human performance

    NASA Technical Reports Server (NTRS)

    Ariel, Gideon

    1994-01-01

    The purpose of this manuscript is to address the issue of muscular activity, human motion, fitness, and exercise. Human activity is reviewed from the historical perspective as well as from the basics of muscular contraction, nervous system controls, mechanics, and biomechanical considerations. In addition, attention has been given to some of the principles involved in developing muscular adaptations through strength development. Brief descriptions and findings from a few studies are included. These experiments were conducted in order to investigate muscular adaptation to various exercise regimens. Different theories of strength development were studied and correlated to daily human movements. All measurement tools used represent state of the art exercise equipment and movement analysis. The information presented here is only a small attempt to understand the effects of exercise and conditioning on Earth with the objective of leading to greater knowledge concerning human responses during spaceflight. What makes life from nonliving objects is movement which is generated and controlled by biochemical substances. In mammals. the controlled activators are skeletal muscles and this muscular action is an integral process composed of mechanical, chemical, and neurological processes resulting in voluntary and involuntary motions. The scope of this discussion is limited to voluntary motion.

  8. Upper Body Muscular Endurance Among Children 2-5 Years.

    ERIC Educational Resources Information Center

    Gabbard, Carl P.; And Others

    The upper body muscular endurance of males and females 2-5 years of age was assessed, and relationships relative to sex, age, endurance and selected anthropometric measures were investigated. None of the relationships were found to be of practical predicative value; while upper body muscular strength increased with age, no significant differences…

  9. Intelligence and cognitive function in children and adolescents with spinal muscular atrophy.

    PubMed

    von Gontard, A; Zerres, K; Backes, M; Laufersweiler-Plass, C; Wendland, C; Melchers, P; Lehmkuhl, G; Rudnik-Schöneborn, S

    2002-02-01

    Spinal muscular atrophy is a chronic disease characterised by loss of motor function. The aim of the study was to analyse cognitive functions in a large group of patients with spinal muscular atrophy. It was hypothesised that their intelligence is comparable to controls, but not above average as previously postulated. Ninety-six children and adolescents with spinal muscular atrophy I-III, aged 6.0-18.11 years, 45 non-affected siblings and 59 healthy, matched controls were examined with one- (CPM/SPM), as well as multi-dimensional intelligence tests (Kaufman-ABC; Wechsler tests). The mean IQ measured with the CPM/SPM tests was 109.6 for the spinal muscular atrophy group, 107.3 for the sibs and 104.1 for the healthy controls (no significant difference). In the older children and adolescents (SPM only) the mean IQ was significantly higher for the spinal muscular atrophy patients (109.6) than for the controls (95.4). The standard score in the 'mental processing composite' scale of the Kaufman-ABC was identical in the spinal muscular atrophy group and controls (103.8). The cognitive profile was relatively homogeneous. However, the older children and adolescents did have a significantly higher verbal IQ (113.8) than controls (104.6) in the Wechsler tests. There were no significant differences in any of the tests among different grades of severity (spinal muscular atrophy types I-III). It can be concluded that children and adolescents with spinal muscular atrophy have a general intelligence in the normal range. By adolescence, environmentally mediated aspects of intelligence are higher in patients with spinal muscular atrophy. It could be speculated that the development of cognitive skills and knowledge is a creative way to compensate the many restrictions due to their physical handicap.

  10. Willingness to Pay for a Newborn Screening Test for Spinal Muscular Atrophy.

    PubMed

    Lin, Pei-Jung; Yeh, Wei-Shi; Neumann, Peter J

    2017-01-01

    The current US mandatory newborn screening panel does not include spinal muscular atrophy, the most common fatal genetic disease among children. We assessed population preferences for newborn screening for spinal muscular atrophy, and how test preferences varied depending on immediate treatment implications. We conducted an online willingness-to-pay survey of US adults (n = 982). Respondents were asked to imagine being parents of a newborn. Each respondent was presented with two hypothetical scenarios following the spinal muscular atrophy screening test: current standard of care (no treatment available) and one of three randomly assigned scenarios (new treatment available to improve functioning, survival, or both). We used a bidding game to elicit willingness to pay for the spinal muscular atrophy test, and performed a two-part model to estimate median and mean willingness-to-pay values. Most respondents (79% to 87%) would prefer screening their newborns for spinal muscular atrophy. People expressed a willingness to pay for spinal muscular atrophy screening even without an available therapy (median: $142; mean: $253). Willingness to pay increased with treatment availability (median: $161 to $182; mean: $270 to $297) and respondent income. Most respondents considered test accuracy, treatment availability, and treatment effectiveness very important or important factors in deciding willingness to pay. Most people would prefer and would be willing to pay for testing their newborn for spinal muscular atrophy, even in the absence of direct treatment. People perceive the spinal muscular atrophy test more valuable if treatment were available to improve the newborn's functioning and survival. Despite preferences for the test information, adding spinal muscular atrophy to newborn screening programs remains controversial. Future studies are needed to determine how early detection may impact long-term patient outcomes. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. An Exploration of the Drive for Muscularity in Adolescent Boys and Girls.

    ERIC Educational Resources Information Center

    McCreary, Donald R.; Sasse, Doris K.

    2000-01-01

    Investigated the drive for muscularity among high school adolescents using the Drive for Muscularity Scale. Results indicated that the scale was reliable. High-drive students were mainly boys trying to gain weight and muscle mass. Drive related to poor self-esteem and higher depression levels among boys, but not girls. Drive for muscularity was…

  12. LAMA2-related myopathy: Frequency among congenital and limb-girdle muscular dystrophies.

    PubMed

    Løkken, Nicoline; Born, Alfred Peter; Duno, Morten; Vissing, John

    2015-10-01

    Muscular dystrophy caused by LAMA2-gene mutations is an autosomal recessive disease typically presenting as a severe, early-onset congenital muscular dystrophy (CMD). However, milder cases with a limb-girdle type muscular dystrophy (LGMD) have been described. In this study, we assessed the frequency and phenotypic spectrum of LAMA2-related muscular dystrophy in CMD (n = 18) and LGMD2 (n = 128) cohorts identified in the last 15 years in eastern Denmark. The medical history, brain-MRI, muscle pathology, muscle laminin-α2 expression, and genetic analyses were assessed. Molecular genetics revealed 2 pathogenic LAMA2 mutations in 5 of 18 CMD and 3 of 128 LGMD patients, corresponding to a LAMA2-mutation frequency of 28% in the CMD and 2.3% in the LGMD cohorts, respectively. This study demonstrates a wide clinical spectrum of LAMA2-related muscular dystrophy and its prevalence in an LGMD2 cohort, which indicates that LAMA2 muscular dystrophy should be included in the LGMD2 nomenclature. © 2015 Wiley Periodicals, Inc.

  13. "The sixth sense": towards a history of muscular sensation.

    PubMed

    Smith, Roger

    2011-01-01

    This paper outlines the history of knowledge about the muscular sense and provides a bibliographic resource for further research. A range of different topics, questions and approaches have interrelated throughout this history, and the discussion clarifies this rather than presenting detailed research in any one area. Part I relates the origin of belief in a muscular sense to empiricist accounts of the contribution of the senses to knowledge from Locke, via the iddologues and other authors, to the second half of the nineteenth century. Analysis paid much attention to touch, first in the context of the theory of vision and then in its own right, which led to naming a distinct muscular sense. From 1800 to the present, there was much debate, the main lines of which this paper introduces, about the nature and function of what turned out to be a complex sense. A number of influential psycho-physiologists, notably Alexander Bain and Herbert Spencer, thought this sense the most primitive and primary of all, the origin of knowledge of world, causation and self as an active subject. Part II relates accounts of the muscular sense to the development of nervous physiology and of psychology. In the decades before 1900, the developing separation of philosophy, psychology and physiology as specialised disciplines divided up questions which earlier writers had discussed under the umbrella heading of muscular sensation. The term'kinaesthesia' came in 1880 and 'proprio-ception' in 1906. There was, all the same, a lasting interest in the argument that touch and muscular sensation are intrinsic to the existence of embodied being in the way the other senses are not. In the wider culture--the arts, sport, the psychophysiology of labour and so on--there were many ways in which people expressed appreciation of the importance of what the anatomist Charles Bell had called 'the sixth sense'.

  14. Muscular system in interna of Peltogaster paguri (Rhizocephala: Peltogastridae).

    PubMed

    Miroliubov, Aleksei A

    2017-03-01

    Rhizocephalan parasites have a peculiar life cycle, and their adults lost almost all traits found usually in Crustacea. Despite some data on anatomy and ultrastructure of interna of Peltogastridae, some crucial aspects of morphology are still unknown. For example, there is only one mentioning of myocytes found in interna of Rhizocephalans (Sacculina carcini). So we aimed at studying the muscular system of the interna of Peltogaster paguri using serial histological sectioning and fluorescent staining (TRITC-labeled phalloidin) with confocal microscopy. Within the wall of the main trunk we found striated muscular fibers. The majority of these fibers form a unidirectional single spiral. There are additional small fibers that connect the coils of the large spiral. The density of muscular fibers is highest near the externa stalk, and the number of muscle fibers decreases towards the distal part of the main trunk. We suggest that such a muscular system could provide peristaltic movements of the main trunk and the transport of nutrients through the interna. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. The red tide toxin, brevetoxin, induces embryo toxicity and developmental abnormalities.

    PubMed Central

    Kimm-Brinson, K L; Ramsdell, J S

    2001-01-01

    Brevetoxins are lipophilic polyether toxins produced by the red tide dinoflagellate Gymnodinium breve, and their neurotoxic effects on adult animals have been documented. In this study, we characterized adverse developmental effects of brevetoxin-1 (PbTx-1) using an exposure paradigm that parallels the maternal oocyte transfer of toxin. Medaka fish (Oryzias latipes) embryos were exposed to PbTx-1 via microinjection of toxin reconstituted in a triolein oil droplet. Embryos microinjected with doses of 0.1-8.0 ng/egg (ppm) of brevetoxin-1 exhibited pronounced muscular activity (hyperkinesis) after embryonic day 4. Upon hatching, morphologic abnormalities were commonly found in embryos at the following lowest adverse effect levels: 1.0-3.0 ppm, lateral curvature of the spinal column; 3.1-3.4 ppm, herniation of brain meninges through defects in the skull; and 3.4-4.0 ppm, malpositioned eye. Hatching abnormalities were also commonly observed at brevetoxin doses of 2.0 ppm and higher with head-first, as opposed to the normal tail-first, hatching, and doses > 4.1 ng/egg produced embryos that developed but failed to hatch. Given the similarity of developmental processes found between higher and lower vertebrates, teratogenic effects of brevetoxins have the potential to occur among different phylogenetic classes. The observation of developmental abnormalities after PbTx-1 exposure identifies a new spectrum of adverse effects that may be expected to occur following exposure to G. breve red tide events. PMID:11335186

  16. Dasatinib as a treatment for Duchenne muscular dystrophy.

    PubMed

    Lipscomb, Leanne; Piggott, Robert W; Emmerson, Tracy; Winder, Steve J

    2016-01-15

    Identification of a systemically acting and universal small molecule therapy for Duchenne muscular dystrophy would be an enormous advance for this condition. Based on evidence gained from studies on mouse genetic models, we have identified tyrosine phosphorylation and degradation of β-dystroglycan as a key event in the aetiology of Duchenne muscular dystrophy. Thus, preventing tyrosine phosphorylation and degradation of β-dystroglycan presents itself as a potential therapeutic strategy. Using the dystrophic sapje zebrafish, we have investigated the use of tyrosine kinase and other inhibitors to treat the dystrophic symptoms in this model of Duchenne muscular dystrophy. Dasatinib, a potent and specific Src tyrosine kinase inhibitor, was found to decrease the levels of β-dystroglycan phosphorylation on tyrosine and to increase the relative levels of non-phosphorylated β-dystroglycan in sapje zebrafish. Furthermore, dasatinib treatment resulted in the improved physical appearance of the sapje zebrafish musculature and increased swimming ability as measured by both duration and distance of swimming of dasatinib-treated fish compared with control animals. These data suggest great promise for pharmacological agents that prevent the phosphorylation of β-dystroglycan on tyrosine and subsequent steps in the degradation pathway as therapeutic targets for the treatment of Duchenne muscular dystrophy. © The Author 2015. Published by Oxford University Press.

  17. Engagement in muscular strengthening activities is associated with better sleep

    PubMed Central

    Loprinzi, Paul D.; Loenneke, Jeremy P.

    2015-01-01

    Few studies have examined whether engagement in muscular strengthening activities is associated with sleep duration, which was the purpose of this study. Data from the population-based 2005–2006 National Health and Nutrition Examination Survey were used, which included an analytic sample of 4386 adults (20–85 yrs). Sleep duration and engagement in muscle strengthening activities was self-reported. After adjustments (including aerobic-based physical activity), those engaging in muscular strength activities, compared to those not engaging in muscular strengthening activities, had an 19% increased odds of meeting sleep guidelines (7–8 h/night) (Odds Ratio = 1.19, 95% Confidence Interval: 1.01–1.38, P = 0.04). Promotion of muscular strengthening activities by clinicians should occur not only for improvements in other aspects of health (e.g., cardiovascular benefits), but also to help facilitate optimal sleep duration. PMID:26844170

  18. The Identification of Carriers in Duchenne Muscular Dystrophy

    PubMed Central

    Monckton, George; Ludvigsen, Bernhard

    1963-01-01

    Following recurrent reports in the literature that it is possible to detect carriers of the gene for progressive muscular dystrophy (Duchenne), a survey of nine families was performed. No unequivocal results could be obtained in comparison of clinical data with circulation-time measurements or serum enzyme studies. It is concluded that carrier-labelling with respect to progressive muscular dystrophy is not yet at a satisfactory stage, although progress is being made. PMID:13935998

  19. Biological, Psychological, and Sociocultural Factors Contributing to the Drive for Muscularity in Weight-Training Men

    PubMed Central

    Schneider, Catharina; Rollitz, Laura; Voracek, Martin; Hennig-Fast, Kristina

    2016-01-01

    The drive for muscularity and associated behaviors (e.g., exercising and dieting) are of growing importance for men in Western societies. In its extreme form, it can lead to body image concerns and harmful behaviors like over-exercising and the misuse of performance-enhancing substances. Therefore, investigating factors associated with the drive for muscularity, especially in vulnerable populations like bodybuilders and weight trainers can help identify potential risk and protective factors for body image problems. Using a biopsychosocial framework, the aim of the current study was to explore different factors associated with drive for muscularity in weight-training men. To this purpose, German-speaking male weight trainers (N = 248) completed an online survey to determine the extent to which biological, psychological, and sociocultural factors contribute to drive for muscularity and its related attitudes and behaviors. Using multiple regression models, findings showed that media ideal body internalization was the strongest positive predictor for drive for muscularity, while age (M = 25.9, SD = 7.4) held the strongest negative association with drive for muscularity. Dissatisfaction with muscularity, but not with body fat, was related to drive for muscularity. The fat-free mass index, a quantification of the actual degree of muscularity of a person, significantly predicted drive for muscularity-related behavior but not attitudes. Body-related aspects of self-esteem, but not global self-esteem, were significant negative predictors of drive for muscularity. Since internalization of media body ideals presented the highest predictive value for drive for muscularity, these findings suggest that media body ideal internalizations may be a risk factor for body image concerns in men, leading, in its most extreme form to disordered eating or muscle dysmorphia. Future research should investigate the relations between drive for muscularity, age, body composition

  20. Drive for muscularity and disordered eating among French adolescent boys: a sociocultural model.

    PubMed

    Rodgers, Rachel F; Ganchou, Camille; Franko, Debra L; Chabrol, Henri

    2012-06-01

    The pursuit of muscularity is an important body image concern among boys which has been described within sociocultural models of risk for eating disorders. This study explored a sociocultural model of disordered eating in which drive for thinness and pursuit of muscularity were both pathways to disordered eating among French adolescent boys. A sample of 146 adolescents completed a questionnaire assessing drive for thinness, drive for muscularity, media-ideal internalization, appearance comparison, and sociocultural pressure. The model was a good fit to the data and both drive for thinness and the pursuit of muscularity were related to disordered eating. Furthermore, internalization and appearance comparison mediated the relationships between pressure to increase muscle and both drive for muscularity and drive for thinness. Longitudinal research could help clarify the role of the pursuit of muscularity in the development of disordered eating and extreme body shape changing behaviors. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. Individual and Partner Risk Factors Associated with Abnormal Cervical Cytology among Women in HIV-discordant Relationships

    PubMed Central

    Soh, Jason; Rositch, Anne F.; Koutsky, Laura; Guthrie, Brandon L.; Choi, Robert Y.; Bosire, Rose K.; Gatuguta, Ann; Smith, Jennifer S.; Kiarie, James; Lohman-Payne, Barbara; Farquhar, Carey

    2014-01-01

    Individual and sexual partner characteristics may increase risk of abnormal cervical cytology among women in HIV-discordant relationships. Papanicolaou smears were obtained in a prospective cohort of Kenyan HIV-discordant couples. Of 441 women, 283 (64%) were HIV-infected and 158 (36%) were HIV-uninfected with HIV-infected partners. Overall, 79 (18%) had low-grade and 25 (6%) high-grade cervical abnormalities. Lack of male circumcision, male HSV-2 seropositivity and lower couple socioeconomic status were associated with cervical abnormalities (p<0.05). HIV-uninfected women with HIV-infected male sex partners (CD4>350 cells/µL) had the lowest prevalence of high-grade cervical lesions. HIV-infected women (CD4>350 cells/µL) and HIV-uninfected women with HIV-infected partners (CD4≤350 cells/µL) were at similar intermediate risk (P>0.05), and HIV-infected women (CD4≤350 cells/µL) had significantly higher risk of high-grade cervical abnormalities (p=0.05). Women in HIV-discordant relationships have high rates of cervical lesions and this may be influenced by couple-level factors, including HIV status and CD4 count of the infected partner. PMID:24047885

  2. Inherited Paediatric Motor Neuron Disorders: Beyond Spinal Muscular Atrophy

    PubMed Central

    Sampaio, Hugo; Mowat, David; Roscioli, Tony

    2017-01-01

    Paediatric motor neuron diseases encompass a group of neurodegenerative diseases characterised by the onset of muscle weakness and atrophy before the age of 18 years, attributable to motor neuron loss across various neuronal networks in the brain and spinal cord. While the genetic underpinnings are diverse, advances in next generation sequencing have transformed diagnostic paradigms. This has reinforced the clinical phenotyping and molecular genetic expertise required to navigate the complexities of such diagnoses. In turn, improved genetic technology and subsequent gene identification have enabled further insights into the mechanisms of motor neuron degeneration and how these diseases form part of a neurodegenerative disorder spectrum. Common pathophysiologies include abnormalities in axonal architecture and function, RNA processing, and protein quality control. This review incorporates an overview of the clinical manifestations, genetics, and pathophysiology of inherited paediatric motor neuron disorders beyond classic SMN1-related spinal muscular atrophy and describes recent advances in next generation sequencing and its clinical application. Specific disease-modifying treatment is becoming a clinical reality in some disorders of the motor neuron highlighting the importance of a timely and specific diagnosis. PMID:28634552

  3. The Role of Adiposity in the Association between Muscular Fitness and Cardiovascular Disease.

    PubMed

    Pérez-Bey, Alejandro; Segura-Jiménez, Víctor; Fernández-Santos, Jorge Del Rosario; Esteban-Cornejo, Irene; Gómez-Martínez, Sonia; Veiga, Oscar L; Marcos, Ascensión; Castro-Piñero, José

    2018-05-11

    To test the associations of muscular fitness and body mass index (BMI), individually and combined, with clustered cardiovascular disease risk factors in children and adolescents and to analyze the mediator role of BMI in the association between muscular fitness and clustered cardiovascular disease risk factors. In total, 239 children (113 girls) and 270 adolescents (128 girls) participated in this cross-sectional study. Height and weight were assessed, and BMI was calculated. A cardiovascular disease risk factors index (CVDRF-I) was created from the combination of the following variables: waist circumference, systolic blood pressure, triglycerides, high-density lipoprotein cholesterol, and glucose. Handgrip strength/weight and standing long jump tests were used to assess muscular fitness. A muscular fitness index was computed from the combination of both tests. Muscular fitness index was associated with CVDRF-I in children of both sexes and adolescent boys; however, these associations disappeared after accounting for BMI. BMI was associated with CVDRF-I in both children and adolescents, even after adjusting for muscular fitness (all P < .001). In male and female children and in adolescent boys, the association between muscular fitness and CVDRF-I was mediated by BMI (all P < .001). Because there was no association between muscular fitness and CVDRF-I in adolescent girls, the mediation hypothesis was discarded. BMI is an independent predictor of CVDRF-I in children and adolescents of both sexes. Conversely, the effect of muscular fitness on CVDRF-I seems to be fully mediated by BMI levels in male and female children and in adolescent boys. Copyright © 2018 Elsevier Inc. All rights reserved.

  4. Implementation of Duchenne Muscular Dystrophy Care Considerations.

    PubMed

    Andrews, Jennifer G; Conway, Kristin; Westfield, Christina; Trout, Christina; Meaney, F John; Mathews, Katherine; Ciafaloni, Emma; Cunniff, Christopher; Fox, Deborah J; Matthews, Dennis; Pandya, Shree

    2018-06-20

    Duchenne muscular dystrophy (DMD) is an X-linked disorder characterized by progressive muscle weakness and multisystem involvement. Recent advances in management of individuals with DMD have prolonged survival. Lack of standardized care spurred an international collaboration to develop consensus-based care considerations for diagnosis and management. In this study, we evaluate adherence to considerations at selected sites. We collaborated with the Muscular Dystrophy Surveillance, Tracking, and Research Network. Our sample included males with DMD and Becker muscular dystrophy <21 years as of December 31, 2010, with 1 health care encounter on or after January 1, 2012. We collected data from medical records on encounters occurring January 1, 2012, through December 31, 2014. Adherence was determined when frequency of visits or assessments were at or above recommendations for selected care considerations. Our analytic sample included 299 individuals, 7% of whom (20/299) were classified as childhood-onset Becker muscular dystrophy. Adherence for neuromuscular and respiratory clinician visits was 65% for the cohort; neuromuscular assessments and corticosteroid side effect monitoring measures ranged from 16% to 68%. Adherence was 83% for forced vital capacity and ≤58% for other respiratory diagnostics. Cardiologist assessments and echocardiograms were found for at least 84%. Transition planning for education or health care was documented for 31% of eligible males. Medical records data were used to identify areas in which practice aligns with the care considerations. However, there remains inconsistency across domains and insufficiency in critical areas. More research is needed to explain this variability and identify reliable methods to measure outcomes. Copyright © 2018 by the American Academy of Pediatrics.

  5. The drive for muscularity in men: media influences and objectification theory.

    PubMed

    Daniel, Samantha; Bridges, Sara K

    2010-01-01

    Presently, objectification theory has yielded mixed results when utilized to explain body image concerns in men. An online survey assessing internalization of media ideals, self-objectification, body surveillance, body shame, the drive for muscularity, and body mass index (BMI) was completed by 244 predominantly college-aged males. Path analyses were used to investigate relationships among these variables where it was hypothesized that objectification variables would mediate the relationship between internalization of media ideals and the drive for muscularity. Internalization of media ideals was the strongest predictor of the drive for muscularity, followed by BMI, though variables of objectification theory had no impact on the drive for muscularity contrary to hypotheses. The results suggest that objectification theory may not be applicable to men as it is currently measured. Copyright 2009 Elsevier Ltd. All rights reserved.

  6. Discrete and continuous joint coupling relationships in uninjured recreational runners.

    PubMed

    Dierks, Tracy A; Davis, Irene

    2007-06-01

    Abnormal joint coupling is thought to be related to overuse injuries in runners. However, researchers do not yet know what constitutes normal joint coupling during running, which makes abnormal coupling difficult to define. Lower extremity kinematics were collected from 40 recreational runners during stance. Joint coupling methods were applied and, for each method, means and both within- and between-subject variability were calculated. The 95% confidence interval was used to compare differences across coupling relationships and periods of stance. Timing between rearfoot eversion, tibial internal rotation, and knee flexion were relatively synchronous while relationships involving knee internal rotation were more asynchronous. The excursion ratios showed that every 2 degrees of rearfoot eversion was coupled with 1 degrees of both tibial internal rotation and knee internal rotation. Vector coding results showed that just beyond maximum loading, all joint coupling relationships resulted in relatively equal amounts of motion, while the within-subject variability was similar throughout stance. The continuous relative phase results showed that the most out-of-phase coupling occurred in the periods around heel-strike and toe-off while the most in-phase coupling occurred in the period just beyond maximum loading of the leg. The continuous relative phase within-subject variability was greatest at the periods around heel-strike and toe-off and smallest just beyond maximum loading. With a better understanding of joint coupling in uninjured runners, these data will help to serve as a reference for future studies investigating the relationship between running injuries and abnormal joint coupling.

  7. Dystrophin quantification and clinical correlations in Becker muscular dystrophy: implications for clinical trials.

    PubMed

    Anthony, Karen; Cirak, Sebahattin; Torelli, Silvia; Tasca, Giorgio; Feng, Lucy; Arechavala-Gomeza, Virginia; Armaroli, Annarita; Guglieri, Michela; Straathof, Chiara S; Verschuuren, Jan J; Aartsma-Rus, Annemieke; Helderman-van den Enden, Paula; Bushby, Katherine; Straub, Volker; Sewry, Caroline; Ferlini, Alessandra; Ricci, Enzo; Morgan, Jennifer E; Muntoni, Francesco

    2011-12-01

    Duchenne muscular dystrophy is caused by mutations in the DMD gene that disrupt the open reading frame and prevent the full translation of its protein product, dystrophin. Restoration of the open reading frame and dystrophin production can be achieved by exon skipping using antisense oligonucleotides targeted to splicing elements. This approach aims to transform the Duchenne muscular dystrophy phenotype to that of the milder disorder, Becker muscular dystrophy, typically caused by in-frame dystrophin deletions that allow the production of an internally deleted but partially functional dystrophin. There is ongoing debate regarding the functional properties of the different internally deleted dystrophins produced by exon skipping for different mutations; more insight would be valuable to improve and better predict the outcome of exon skipping clinical trials. To this end, we have characterized the clinical phenotype of 17 patients with Becker muscular dystrophy harbouring in-frame deletions relevant to on-going or planned exon skipping clinical trials for Duchenne muscular dystrophy and correlated it to the levels of dystrophin, and dystrophin-associated protein expression. The cohort of 17 patients, selected exclusively on the basis of their genotype, included 4 asymptomatic, 12 mild and 1 severe patient. All patients had dystrophin levels of >40% of control and significantly higher dystrophin (P = 0.013), β-dystroglycan (P = 0.025) and neuronal nitric oxide synthase (P = 0.034) expression was observed in asymptomatic individuals versus symptomatic patients with Becker muscular dystrophy. Furthermore, grouping the patients by deletion, patients with Becker muscular dystrophy with deletions with an end-point of exon 51 (the skipping of which could rescue the largest group of Duchenne muscular dystrophy deletions) showed significantly higher dystrophin levels (P = 0.034) than those with deletions ending with exon 53. This is the first quantitative study on both

  8. Dystrophin quantification and clinical correlations in Becker muscular dystrophy: implications for clinical trials

    PubMed Central

    Anthony, Karen; Cirak, Sebahattin; Torelli, Silvia; Tasca, Giorgio; Feng, Lucy; Arechavala-Gomeza, Virginia; Armaroli, Annarita; Guglieri, Michela; Straathof, Chiara S.; Verschuuren, Jan J.; Aartsma-Rus, Annemieke; Helderman-van den Enden, Paula; Bushby, Katherine; Straub, Volker; Sewry, Caroline; Ferlini, Alessandra; Ricci, Enzo; Morgan, Jennifer E.

    2011-01-01

    Duchenne muscular dystrophy is caused by mutations in the DMD gene that disrupt the open reading frame and prevent the full translation of its protein product, dystrophin. Restoration of the open reading frame and dystrophin production can be achieved by exon skipping using antisense oligonucleotides targeted to splicing elements. This approach aims to transform the Duchenne muscular dystrophy phenotype to that of the milder disorder, Becker muscular dystrophy, typically caused by in-frame dystrophin deletions that allow the production of an internally deleted but partially functional dystrophin. There is ongoing debate regarding the functional properties of the different internally deleted dystrophins produced by exon skipping for different mutations; more insight would be valuable to improve and better predict the outcome of exon skipping clinical trials. To this end, we have characterized the clinical phenotype of 17 patients with Becker muscular dystrophy harbouring in-frame deletions relevant to on-going or planned exon skipping clinical trials for Duchenne muscular dystrophy and correlated it to the levels of dystrophin, and dystrophin-associated protein expression. The cohort of 17 patients, selected exclusively on the basis of their genotype, included 4 asymptomatic, 12 mild and 1 severe patient. All patients had dystrophin levels of >40% of control and significantly higher dystrophin (P = 0.013), β-dystroglycan (P = 0.025) and neuronal nitric oxide synthase (P = 0.034) expression was observed in asymptomatic individuals versus symptomatic patients with Becker muscular dystrophy. Furthermore, grouping the patients by deletion, patients with Becker muscular dystrophy with deletions with an end-point of exon 51 (the skipping of which could rescue the largest group of Duchenne muscular dystrophy deletions) showed significantly higher dystrophin levels (P = 0.034) than those with deletions ending with exon 53. This is the first quantitative

  9. Atrophy, fibrosis, and increased PAX7-positive cells in pharyngeal muscles of oculopharyngeal muscular dystrophy patients.

    PubMed

    Gidaro, Teresa; Negroni, Elisa; Perié, Sophie; Mirabella, Massimiliano; Lainé, Jeanne; Lacau St Guily, Jean; Butler-Browne, Gillian; Mouly, Vincent; Trollet, Capucine

    2013-03-01

    Oculopharyngeal muscular dystrophy (OPMD) is a late-onset autosomal dominant inherited dystrophy caused by an abnormal trinucleotide repeat expansion in the poly(A)-binding-protein-nuclear 1 (PABPN1) gene. Primary muscular targets of OPMD are the eyelid elevator and pharyngeal muscles, including the cricopharyngeal muscle (CPM), the progressive involution of which leads to ptosis and dysphagia, respectively. To understand the consequences of PABPN1 polyalanine expansion in OPMD, we studied muscle biopsies from 14 OPMD patients, 3 inclusion body myositis patients, and 9 healthy controls. In OPMD patient CPM (n = 6), there were typical dystrophic features with extensive endomysial fibrosis and marked atrophy of myosin heavy-chain IIa fibers. There were more PAX7-positive cells in all CPM versus other muscles (n = 5, control; n = 3, inclusion body myositis), and they were more numerous in OPMD CPM versus control normal CPM without any sign of muscle regeneration. Intranuclear inclusions were present in all OPMD muscles but unaffected OPMD patient muscles (i.e. sternocleidomastoid, quadriceps, or deltoid; n = 14) did not show evidence of fibrosis, atrophy, or increased PAX7-positive cell numbers. These results suggest that the specific involvement of CPM in OPMD might be caused by failure of the regenerative response with dysfunction of PAX7-positive cells and exacerbated fibrosis that does not correlate with the presence of PABPN1 inclusions.

  10. Ehlers-Danlos Syndrome Type VI in a 17-Year-Old Iranian Boy with Severe Muscular Weakness – A Diagnostic Challenge?

    PubMed Central

    Kariminejad, Ariana; Bozorgmehr, Bita; Khatami, Alireza; Kariminejad, Mohamad-Hasan; Giunta, Cecilia; Steinmann, Beat

    2010-01-01

    Background The Ehlers-Danlos syndrome type VI (EDSVI) is an autosomal recessive connective tissue disease which is characterized by severe hypotonia at birth, progressive kyphoscoliosis, skin hyperelasticity and fragility, joint hypermobility and (sub-)luxations, microcornea, rupture of arteries and the eye globe, and osteopenia. The enzyme collagen lysyl hydroxylase (LH1) is deficient in these patients due to mutations in the PLOD1 gene. Case Presentation We report a 17-year-old boy, born to related parents, with severe kyphoscoliosis, scar formation, joint hypermobility and multiple dislocations, muscular weakness, rupture of an ocular globe, and a history of severe infantile hypotonia. EDS VI was suspected clinically and confirmed by an elevated ratio of urinary total lysyl pyridinoline to hydroxylysyl pyridinoline, abnormal electrophoretic mobility of the α-collagen chains, and mutation analysis. Conclusion Because of the high rate of consanguineous marriages in Iran and, as a consequence thereof, an increased rate of autosomal recessive disorders, we urge physicians to consider EDS VI in the differential diagnosis of severe infantile hypotonia and muscular weakness, a disorder which can easily be confirmed by the analysis of urinary pyridinolines that is highly specific, sensitive, robust, fast, non-invasive, and inexpensive. PMID:23056730

  11. Genetics and emerging treatments for Duchenne and Becker muscular dystrophy.

    PubMed

    Wein, Nicolas; Alfano, Lindsay; Flanigan, Kevin M

    2015-06-01

    Mutations in the DMD gene result in Duchenne or Becker muscular dystrophy due to absent or altered expression of the dystrophin protein. The more severe Duchenne muscular dystrophy typically presents around ages 2 to 5 with gait disturbance, and historically has led to the loss of ambulation by age 12. It is important for the practicing pediatrician, however, to be aware of other presenting signs, such as delayed motor or cognitive milestones, or elevated serum transaminases. Becker muscular dystrophy is milder, often presenting after age 5, with ambulation frequently preserved past 20 years and sometimes into late decades. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Abnormal short-latency synaptic plasticity in the motor cortex of subjects with Becker muscular dystrophy: a rTMS study.

    PubMed

    Golaszewski, Stefan; Schwenker, Kerstin; Bergmann, Jürgen; Brigo, Francesco; Christova, Monica; Trinka, Eugen; Nardone, Raffaele

    2016-01-01

    We used repetitive transcranial magnetic stimulation (rTMS) to further investigate motor cortex excitability in 13 patients with Becker muscular dystrophy (BMD), six of them with slight mental retardation. RTMS delivered at 5Hz frequency and suprathreshold intensity progressively increases the size of motor evoked potentials (MEPs) in healthy subjects; the rTMS-induced facilitation of MEPs was significantly reduced in the BMD patients mentally retarded or classified as borderline when compared with age-matched control subjects and the BMD patients with normal intelligence. The increase in the duration of the cortical silent period was similar in both patient groups and controls. These findings suggest an altered cortical short-term synaptic plasticity in glutamate-dependent excitatory circuits within the motor cortex in BMD patients with intellectual disabilities. RTMS studies may shed new light on the physiological mechanisms of cortical involvement in dystrophinopathies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  13. Magnetic testing for inter-granular crack defect of tubing coupling

    NASA Astrophysics Data System (ADS)

    Hu, Bo; Yu, Runqiao

    2018-04-01

    This study focused on the inter-granular crack defects of tubing coupling wherein a non-destructive magnetic testing technique was proposed to determine the magnetic flux leakage features on coupling surface in the geomagnetic field using a high-precision magnetic sensor. The abnormal magnetic signatures of defects were analysed, and the principle of the magnetic test was explained based on the differences in the relative permeability of defects and coupling materials. Abnormal fluctuations of the magnetic signal were observed at the locations of the inter-granular crack defects. Imaging showed the approximate position of defects. The test results were proven by metallographic phase.

  14. A prospective investigation of interpersonal influences on the pursuit of muscularity in late adolescent boys and girls.

    PubMed

    Shomaker, Lauren B; Furman, Wyndol

    2010-04-01

    This project examined whether interpersonal pressure to be muscular predicted late adolescents' pursuit of muscularity. Participants were 199 adolescents (16-19 years), mothers (n = 175), and friends (n = 159), assessed at two annual times. Pressure to be muscular was assessed with adolescents', mothers', and friends' reports of their relationships. Adolescents reported pressure from fathers and romantic partners, appearance satisfaction, disordered eating, and pursuit of muscularity. Adolescents', mothers', and friends' reports of pressure related to pursuit of muscularity at both times. Adolescents' perceptions and mothers' reports prospectively predicted pursuit of muscularity. Findings highlight the relevance of relationships to pursuit of muscularity in late adolescents.

  15. Men, Muscles, and Eating Disorders: an Overview of Traditional and Muscularity-Oriented Disordered Eating.

    PubMed

    Lavender, Jason M; Brown, Tiffany A; Murray, Stuart B

    2017-06-01

    There is growing recognition that eating disorder (ED) symptoms, particularly those of a muscularity-oriented nature, are more common in men than previously understood. The purpose of the current review is to describe contemporary directions and implications of research on traditional and muscularity-oriented ED symptoms among males. Evidence indicates that ED symptoms occur in a substantial minority of men. Importantly, recent research has focused on muscularity-oriented body image and disordered eating in males, demonstrating the prevalence, correlates, and consequences of maladaptive muscularity-oriented attitudes and behaviors. A growing number of assessments are available to measure these constructs in males, and preliminary treatment considerations have begun to be addressed in the literature. Research on male EDs and body image is increasingly focusing on muscularity-oriented manifestations. Continued empirical work will be critical to improve our understanding of the onset, maintenance, and treatment of muscularity-oriented disordered eating in males.

  16. Porcine models of muscular dystrophy

    USDA-ARS?s Scientific Manuscript database

    Duchenne muscular dystrophy is a progressive, fatal, X-linked disease caused by a failure to accumulate the cytoskeletal protein, dystrophin. This disease is modeled by a variety of animal models including several fish models, mice, rats, and dogs. While these models have contributed substantially t...

  17. Predicting muscularity-related behavior, emotions, and cognitions in men: The role of psychological need thwarting, drive for muscularity, and mesomorphic internalization.

    PubMed

    Edwards, Christian; Tod, David; Molnar, Gyozo; Markland, David

    2016-09-01

    We examine the relationships that internalization, need thwarting (NT), and drive for muscularity (DFM), along with their interactions, had with weightlifting, muscle dissatisfaction (MD), and muscle-related-worry (MRW). A sample of 552 men (MAge=20.5 years, SD=3.1) completed the Psychological Need Thwarting Scale, the Internalization subscale of the male version of the Sociocultural Attitudes Towards Appearance Questionnaire, the Drive for Muscularity Scale-Attitudes subscale, the Male Body Attitudes Scale-Muscularity subscale, the Body Change Inventory-Worry subscale, and an inventory assessing weightlifting behavior. DFM significantly predicted weightlifting, MRW, and MD. Internalization significantly predicted weightlifting and MRW. NT significantly predicted weightlifting and MD, and its relationship with MRW approached significance. The interaction terms did not predict weightlifting or MRW. The NT/DFM and NT/Internalization interaction terms predicted MD. These results highlight the role of NT in predicting appearance variables in men. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Thinness and muscularity internalization: Associations with disordered eating and muscle dysmorphia in men.

    PubMed

    Klimek, Patrycja; Murray, Stuart B; Brown, Tiffany; Gonzales Iv, Manuel; Blashill, Aaron J

    2018-04-01

    The tripartite influence model of body image identifies internalization of societal body ideals as a risk factor for developing body dissatisfaction, and subsequent disordered eating behavior. In men, internalization of two dimensions of body image ideals, thinness and muscularity, is associated with body dissatisfaction and eating concerns. However, it is unknown how thinness and muscularity internalization interact in predicting muscle dysmorphia and disordered eating in men. Data were collected online from 180 undergraduate men, with ages ranging from 18 to 33 years (19.6, SD = 2.6). Regression models were used to test the interactive effects of thinness and muscularity internalization on (a) muscle dysmorphia symptoms and (b) disordered eating. Subsequent simple slope analyses probed effects at the mean, and ±1 standard deviation of thinness internalization. Muscularity and thinness internalization were independently positively related to muscle dysmorphia symptoms and disordered eating. Additionally, a significant interaction revealed that muscularity internalization was increasingly related to muscle dysmorphia symptoms as thinness internalization decreased. Men who internalized the muscular ideal had higher levels of muscle dysmorphia when they did not highly internalize the thin ideal. However, greater internalization of both the muscularity and thin ideal independently may be most relevant in the development of disordered eating in men. Future research is needed to explore variability in experiences of muscle dysmorphia compared with disordered eating in males. © 2018 Wiley Periodicals, Inc.

  19. Determinants of the epithelial-muscular axis on embryonic stem cell-derived gut-like structures.

    PubMed

    Luo, Yi; Takaki, Miyako; Misawa, Hiromi; Matsuyoshi, Hiroko; Sasahira, Tomonori; Chihara, Yoshitomo; Fujii, Kiyomu; Ohmori, Hitoshi; Kuniyasu, Hiroki

    2010-01-01

    Dome-like structures with epithelial-muscular layers resembling the gut have been derived from mouse embryonic stem (ES) cells. These domes have been reported to show spontaneous contractions and are called ES gut. In the present study, we examined the epithelial-muscular axis of these domes by detecting differentiation markers. A normal epithelial-muscular axis was exhibited in the domes with spontaneous motility, whereas the domes without spontaneous motility showed either an inverted or obscure axis. To investigate the factors affecting the epithelial-muscular axis, we examined the expression of hedgehog signaling factors in the domes. Expression of hedgehog family factors was detected in the epithelial components of the domes with motility, whereas this expression was inverted or obscure in the domes without motility. Out of the 25 domes, 10 of the 10 motility (+) domes showed a normal epithelial-muscular axis, whereas 14 of the 15 motility (-) domes lacked a normal epithelial-muscular axis. This implies that activin A upregulated the expression of sonic hedgehog and intestinal alkaline phosphatase in the embryoid bodies. These findings suggest that the motility of the ES gut depends on the domes' epithelial-muscular axis. Copyright © 2010 S. Karger AG, Basel.

  20. A Prospective Investigation of Interpersonal Influences on the Pursuit of Muscularity in Late Adolescent Boys and Girls

    PubMed Central

    Shomaker, Lauren B.; Furman, Wyndol

    2010-01-01

    This project examined whether interpersonal pressure to be muscular predicted late adolescents’ pursuit of muscularity. Participants were 199 adolescents (16–19 years), mothers (n=175), and friends (n=159), assessed at two annual times. Pressure to be muscular was assessed with adolescents’, mothers’, and friends’ reports of their relationships. Adolescents reported pressure from fathers and romantic partners, appearance satisfaction, disordered eating, and pursuit of muscularity. Adolescents,’ mothers’, and friends’ reports of pressure related to pursuit of muscularity at both times. Adolescents’ perceptions and mothers’ reports prospectively predicted pursuit of muscularity. Findings highlight the relevance of relationships to pursuit of muscularity in late adolescents. PMID:20348360

  1. Learning about Spinal Muscular Atrophy

    MedlinePlus

    ... causes the disorder. Top of page NHGRI Clinical Research on Spinal Muscular Atrophy Currently, NHGRI is not conducting studies on SMA. The National Institutes of Health is conducting clinical trials identified as enrolling individuals with SMA: Quantitative Analysis of SMN1 and SMN2 Gene Based on ...

  2. Some Dynamics of Personality Development in Boys Suffering from Muscular Dystrophy

    ERIC Educational Resources Information Center

    Mearig, Judith S.

    1973-01-01

    Discussed are personality aspects of Duchenne or pseudohypertrophic muscular dystrophy, a progressive wasting of muscular tissue, which afflicts only boys, and usually has its noticeable onset before the age of 6 years; and described is the development of three male dystrophic siblings. (DB)

  3. [Atypical reaction to anesthesia in Duchenne/Becker muscular dystrophy].

    PubMed

    Silva, Helga Cristina Almeida da; Hiray, Marcia; Vainzof, Mariz; Schmidt, Beny; Oliveira, Acary Souza Bulle; Amaral, José Luiz Gomes do

    2017-05-31

    Duchenne/Becker muscular dystrophy affects skeletal muscles and leads to progressive muscle weakness and risk of atypical anesthetic reactions following exposure to succinylcholine or halogenated agents. The aim of this report is to describe the investigation and diagnosis of a patient with Becker muscular dystrophy and review the care required in anesthesia. Male patient, 14 years old, referred for hyperCKemia (chronic increase of serum creatine kinase levels - CK), with CK values of 7,779-29,040IU.L -1 (normal 174IU.L -1 ). He presented with a discrete delay in motor milestones acquisition (sitting at 9 months, walking at 18 months). He had a history of liver transplantation. In the neurological examination, the patient showed difficulty in walking on one's heels, myopathic sign (hands supported on the thighs to stand), high arched palate, calf hypertrophy, winged scapulae, global muscle hypotonia and arreflexia. Spirometry showed mild restrictive respiratory insufficiency (forced vital capacity: 77% of predicted). The in vitro muscle contracture test in response to halothane and caffeine was normal. Muscular dystrophy analysis by Western blot showed reduced dystrophin (20% of normal) for both antibodies (C and N-terminal), allowing the diagnosis of Becker muscular dystrophy. On preanesthetic assessment, the history of delayed motor development, as well as clinical and/or laboratory signs of myopathy, should encourage neurological evaluation, aiming at diagnosing subclinical myopathies and planning the necessary care to prevent anesthetic complications. Duchenne/Becker muscular dystrophy, although it does not increase susceptibility to MH, may lead to atypical fatal reactions in anesthesia. Copyright © 2017 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

  4. Muscular Dystrophies at Different Ages: Metabolic and Endocrine Alterations

    PubMed Central

    Cruz Guzmán, Oriana del Rocío; Chávez García, Ana Laura; Rodríguez-Cruz, Maricela

    2012-01-01

    Common metabolic and endocrine alterations exist across a wide range of muscular dystrophies. Skeletal muscle plays an important role in glucose metabolism and is a major participant in different signaling pathways. Therefore, its damage may lead to different metabolic disruptions. Two of the most important metabolic alterations in muscular dystrophies may be insulin resistance and obesity. However, only insulin resistance has been demonstrated in myotonic dystrophy. In addition, endocrine disturbances such as hypogonadism, low levels of testosterone, and growth hormone have been reported. This eventually will result in consequences such as growth failure and delayed puberty in the case of childhood dystrophies. Other consequences may be reduced male fertility, reduced spermatogenesis, and oligospermia, both in childhood as well as in adult muscular dystrophies. These facts all suggest that there is a need for better comprehension of metabolic and endocrine implications for muscular dystrophies with the purpose of developing improved clinical treatments and/or improvements in the quality of life of patients with dystrophy. Therefore, the aim of this paper is to describe the current knowledge about of metabolic and endocrine alterations in diverse types of dystrophinopathies, which will be divided into two groups: childhood and adult dystrophies which have different age of onset. PMID:22701119

  5. A rare subclinical or mild type of Becker muscular dystrophy caused by a single exon 48 deletion of the dystrophin gene.

    PubMed

    Zimowski, Janusz G; Pilch, Jacek; Pawelec, Magdalena; Purzycka, Joanna K; Kubalska, Jolanta; Ziora-Jakutowicz, Karolina; Dudzińska, Magdalena; Zaremba, Jacek

    2017-08-01

    In the material of 227 families with Becker muscular dystrophy (BMD), we found nine non-consanguineous families with 17 male individuals carrying a rare mutation-a single exon 48 deletion of the dystrophin gene-who were affected with a very mild or subclinical form of BMD. They were usually detected thanks to accidental findings of elevated serum creatine phosphokinase (sCPK). A thorough clinical analysis of the carriers, both children (12) and adults (5), revealed in some of them muscle hypotonia (10/17) and/or very mild muscle weakness (9/17), as well as decreased tendon reflexes (6/17). Adults, apart from very mild muscle weakness and calf hypertrophy in some, had no significant abnormalities on neurological assessments and had good exercise tolerance. Parents of the children carriers of the exon 48 deletion are usually unaware of their children being affected, and possibly at risk of developing life-threatening cardiomyopathy. The same concerns the adult male carriers. Therefore, the authors postulate undertaking preventive measures such as cascade screening of the relatives of the probands. Newborn screening programmes of Duchenne muscular dystrophy (DMD)/BMD based on sCPK marked increase may be considered.

  6. Muscular forearm activation in hand-grip tasks with superimposition of mechanical vibrations.

    PubMed

    Fattorini, L; Tirabasso, A; Lunghi, A; Di Giovanni, R; Sacco, F; Marchetti, E

    2016-02-01

    The purpose of this paper is to evaluate the muscular activation of the forearm, with or without vibration stimuli at different frequencies while performing a grip tasks of 45s at various level of exerted force. In 16 individuals, 9 females and 7 males, the surface electromyogram (EMG) of extensor carpi radialis longus and the flexor carpi ulnari muscles were assessed. At a short latency from onset EMG, RMS and the level of MU synchronization were assessed to evaluate the muscular adaptations. Whilst a trend of decay of EMG Median frequency (MDFd) was employed as an index of muscular fatigue. Muscular tasks consists of the grip of an instrumented handle at a force level of 20%, 30%, 40%, 60% of the maximum voluntary force. Vibration was supplied by a shaker to the hand in mono-frequential waves at 20, 30, 33 and 40Hz. In relation to EMG, RMS and MU synchronization, the muscular activation does not seem to change with the superimposition of the mechanical vibrations, on the contrary a lower MDFd was observed at 33Hz than in absence of vibration. This suggests an early muscular fatigue induced by vibration due to the fact that 33Hz is a resonance frequency for the hand-arm system. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Bortezomib partially improves laminin α2 chain-deficient muscular dystrophy.

    PubMed

    Körner, Zandra; Fontes-Oliveira, Cibely C; Holmberg, Johan; Carmignac, Virginie; Durbeej, Madeleine

    2014-05-01

    Congenital muscular dystrophy, caused by mutations in LAMA2 (the gene encoding laminin α2 chain), is a severe and incapacitating disease for which no therapy is yet available. We have recently demonstrated that proteasome activity is increased in laminin α2 chain-deficient muscle and that treatment with the nonpharmaceutical proteasome inhibitor MG-132 reduces muscle pathology in laminin α2 chain-deficient dy(3K)/dy(3K) mice. Here, we explore the use of the selective and therapeutic proteasome inhibitor bortezomib (currently used for treatment of relapsed multiple myeloma and mantle cell lymphoma) in dy(3K)/dy(3K) mice and in congenital muscular dystrophy type 1A muscle cells. Outcome measures included quantitative muscle morphology, gene and miRNA expression analyses, proteasome activity, motor activity, and survival. Bortezomib improved several histological hallmarks of disease, partially normalized miRNA expression (miR-1 and miR-133a), and enhanced body weight, locomotion, and survival of dy(3K)/dy(3K) mice. In addition, bortezomib reduced proteasome activity in congenital muscular dystrophy type 1A myoblasts and myotubes. These findings provide evidence that the proteasome inhibitor bortezomib partially reduces laminin α2 chain-deficient muscular dystrophy. Investigation of the clinical efficacy of bortezomib administration in congenital muscular dystrophy type 1A clinical trials may be warranted. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  8. A preliminary study of muscular artifact cancellation in single-channel EEG.

    PubMed

    Chen, Xun; Liu, Aiping; Peng, Hu; Ward, Rabab K

    2014-10-01

    Electroencephalogram (EEG) recordings are often contaminated with muscular artifacts that strongly obscure the EEG signals and complicates their analysis. For the conventional case, where the EEG recordings are obtained simultaneously over many EEG channels, there exists a considerable range of methods for removing muscular artifacts. In recent years, there has been an increasing trend to use EEG information in ambulatory healthcare and related physiological signal monitoring systems. For practical reasons, a single EEG channel system must be used in these situations. Unfortunately, there exist few studies for muscular artifact cancellation in single-channel EEG recordings. To address this issue, in this preliminary study, we propose a simple, yet effective, method to achieve the muscular artifact cancellation for the single-channel EEG case. This method is a combination of the ensemble empirical mode decomposition (EEMD) and the joint blind source separation (JBSS) techniques. We also conduct a study that compares and investigates all possible single-channel solutions and demonstrate the performance of these methods using numerical simulations and real-life applications. The proposed method is shown to significantly outperform all other methods. It can successfully remove muscular artifacts without altering the underlying EEG activity. It is thus a promising tool for use in ambulatory healthcare systems.

  9. Emerging strategies for cell and gene therapy of the muscular dystrophies

    PubMed Central

    Muir, Lindsey A.; Chamberlain, Jeffrey S.

    2016-01-01

    The muscular dystrophies are a heterogeneous group of over 40 disorders that are characterised by muscle weakness and wasting. The most common are Duchenne muscular dystrophy and Becker muscular dystrophy, which result from mutations within the gene encoding dystrophin; myotonic dystrophy type 1, which results from an expanded trinucleotide repeat in the myotonic dystrophy protein kinase gene; and facioscapulohumeral dystrophy, which is associated with contractions in the subtelomeric region of human chromosome 1. Currently the only treatments involve clinical management of symptoms, although several promising experimental strategies are emerging. These include gene therapy using adeno-associated viral, lentiviral and adenoviral vectors and nonviral vectors, such as plasmid DNA. Exon-skipping and cell-based therapies have also shown promise in the effective treatment and regeneration of dystrophic muscle. The availability of numerous animal models for Duchenne muscular dystrophy has enabled extensive testing of a wide range of therapeutic approaches for this type of disorder. Consequently, we focus here on the therapeutic developments for Duchenne muscular dystrophy as a model of the types of approaches being considered for various types of dystrophy. We discuss the advantages and limitations of each therapeutic strategy, as well as prospects and recent successes in the context of future clinical applications. PMID:19555515

  10. Duane retraction syndrome in a patient with Duchenne muscular dystrophy.

    PubMed

    Bosley, Thomas M; Salih, Mustafa A; Alkhalidi, Hisham; Oystreck, Darren T; El Khashab, Heba Y; Kondkar, Altaf A; Abu-Amero, Khaled K

    2016-09-01

    We describe the clinical features of a boy with bilateral Duane retraction syndrome (DRS), Duchenne muscular dystrophy (DMD), and other medical problems. The child was followed-up for five years; his chart was reviewed, including the results of a muscle biopsy and genetic testing. Multiplex ligation-dependent probe amplification (MLPA) was used to interrogate deletions/duplications in the dystrophin gene. The proband had bilateral DRS with otherwise normal ocular motility; he also had developmental delay, mild mental retardation, and seizures. Clinical diagnosis of DMD included progressive proximal weakness, highly elevated creatine kinase levels, and a muscle biopsy showing significant dystrophic changes including contracted, degenerative, and regenerative fibers, and negative dystrophin immunostaining. MLPA documented duplication of exons 3 and 4 of the dystrophin gene. This boy is the third patient to be reported with DRS and DMD, the second with bilateral DRS and the only one with other neurologic features. Mutated dystrophin is present in extraocular muscles and in the central nervous system (CNS) in DMD, leaving open the question of whether this co-occurrence is the result of the genetic muscle abnormality, CNS effects caused by dystrophin mutations, or chance.

  11. The pursuit of muscularity among adolescent boys in Fiji and Tonga.

    PubMed

    Ricciardelli, Lina A; McCabe, Marita P; Mavoa, Helen; Fotu, Kalesita; Goundar, Ramneek; Schultz, Jimaima; Waqa, Gade; Swinburn, Boyd A

    2007-12-01

    The desire for muscularity is tied to Western views of the male gender role, which prescribe that men be strong, physically fit and athletically successful. Although, these ideals have been primarily studied among Western adolescent boys, there is emerging evidence that the same ideals are valued and promoted among males from the Pacific Islands. The aim of the present study was to examine body image concerns associated with muscularity and the reasons for these concerns among Fijian and Tongan adolescent boys. Semi-structured interviews were conducted with 24 Indigenous Fijian, 24 Indo-Fijian, and 24 Tongan boys aged between 13 and 20 years. A thematic analysis of boys' narratives showed that the pursuit of muscularity was a dominant theme for many boys. Boys' reasons for pursing muscularity included the attainment of strength and fitness, sporting performance, physical work, dominance, and health. These findings are examined in relation to previous research with Western adolescent boys.

  12. Histology, composition, and quality traits of chicken Pectoralis major muscle affected by wooden breast abnormality.

    PubMed

    Soglia, F; Mudalal, S; Babini, E; Di Nunzio, M; Mazzoni, M; Sirri, F; Cavani, C; Petracci, M

    2016-03-01

    Only a few years ago, the poultry industry began to face a recent abnormality in breast meat, known as wooden breast, which frequently overlaps with white striping. This study aimed to assess the impact of wooden breast abnormality on quality traits of meat. For this purpose, 32 normal (NRM), 32 wooden (WB), and 32 wooden and white-striped (WB/WS) Pectoralis major muscles were selected from the same flock of heavy broilers (males, Ross 708, weighing around 3.7 kg) in the deboning area of a commercial processing plant at 3 h postmortem and used to assess histology, proximate (moisture, protein, fat, ash, and collagen) and mineral composition (Mg, K, P, Na and Ca), sarcoplasmic and myofibrillar protein patterns, and technological traits of breast meat. Compared to the normal group, WB/WS fillets showed more severe histological lesions characterized by fiber degeneration, fibrosis, and lipidosis, coupled with a significantly harder texture. With regard to proximate and mineral composition, abnormal samples exhibited significantly (P < 0.001) higher moisture, fat, and collagen contents coupled with lower (P < 0.001) amounts of protein and ash. Furthermore, increased calcium (131 vs. 84 mg kg(-1); P < 0.05) and sodium (741 vs. 393 mg kg(-1); P < 0.001) levels were found in WB/WS meat samples. The SDS-PAGE analysis revealed a significantly lower amount of calcium-ATPase (SERCA, 114 kDa), responsible for the translocation of Ca ions across the membrane, in normal breasts compared to abnormal ones. As for meat quality traits, fillets affected by wooden abnormality exhibited significantly (P < 0.001) higher ultimate pH and lower water-holding/water-binding capacity. In particular, compared to normal, abnormal samples showed reduced marinade uptake coupled with increased drip loss and cooking losses as well. In conclusion, this study revealed that meat affected by wooden breast or both wooden breast and white striping abnormalities exhibit poorer nutritional value, harder

  13. Cardio-Muscular Conditioner

    NASA Technical Reports Server (NTRS)

    1993-01-01

    In the mid-sixties, Gary Graham, a Boeing designer, developed a cardiovascular conditioner for a planned Air Force orbiting laboratory. After the project was cancelled, Graham participated in space station conditioning studies for the Skylab program. Twenty years later, he used this expertise to develop the Shuttle 2000-1, a physical therapy and athletic development conditioner, available through Contemporary Designs. The machine is used by football teams, sports clinics and medical rehabilitation centers. Cardiovascular fitness and muscular strength development are promoted through both kinetic and plyometric exercises.

  14. Eteplirsen in the treatment of Duchenne muscular dystrophy

    PubMed Central

    Lim, Kenji Rowel Q; Maruyama, Rika; Yokota, Toshifumi

    2017-01-01

    Duchenne muscular dystrophy is a fatal neuromuscular disorder affecting around one in 3,500–5,000 male births that is characterized by progressive muscular deterioration. It is inherited in an X-linked recessive fashion and is caused by loss-of-function mutations in the DMD gene coding for dystrophin, a cytoskeletal protein that stabilizes the plasma membrane of muscle fibers. In September 2016, the US Food and Drug Administration granted accelerated approval for eteplirsen (or Exondys 51), a drug that acts to promote dystrophin production by restoring the translational reading frame of DMD through specific skipping of exon 51 in defective gene variants. Eteplirsen is applicable for approximately 14% of patients with DMD mutations. This article extensively reviews and discusses the available information on eteplirsen to date, focusing on pharmacological, efficacy, safety, and tolerability data from preclinical and clinical trials. Issues faced by eteplirsen, particularly those relating to its efficacy, will be identified. Finally, the place of eteplirsen and exon skipping as a general therapeutic strategy in Duchenne muscular dystrophy treatment will be discussed. PMID:28280301

  15. Experiments on Factors That Influence Muscular Function in Man.

    DTIC Science & Technology

    1983-05-25

    of phentolamine or phenylephrine did not affect the increase in mean arterial blood pressure , which reached the same high levels at fatigue in all...CLASSIFICATION OF THIS PAGE(Whon Date Elrered) same when the contractions result in muscular fatigue, at which time the mean . blood pressure is the same as it is...arterial blood pressure of bout 150 mmHg at the point of muscular fatigue. Clearly, some vaso- constrictp> response was intervening since the blood flow

  16. Muscular strength is associated with self-esteem in college men but not women.

    PubMed

    Ciccolo, Joseph T; SantaBarbara, Nicholas J; Dunsiger, Shira I; Busch, Andrew M; Bartholomew, John B

    2016-12-01

    Muscular strength is a well-known predictor of morbidity and mortality. Similarly, self-esteem is a predictor of health and well-being. The relationship between these two variables, however, is currently unknown. This study examined the cross-sectional relationship between maximal muscular strength (i.e. handgrip and one-repetition-maximum (1-RM) squat) and global self-esteem in 126 college students. Significant correlations were found between both measures of muscular strength and self-esteem. Further analyses revealed that these relationships were only significant for men. Based on these results, additional research is needed to further explore the relationship between muscular strength and self-esteem, especially in other demographic groups and longitudinally. © The Author(s) 2015.

  17. Advanced Gene Therapy for Treatment of Cardiomyopathy and Respiratory Insufficiency in Duchenne Muscular Dystrophy

    DTIC Science & Technology

    2014-09-01

    TITLE: Advanced Gene Therapy for Treatment of Cardiomyopathy and Respiratory Insufficiency in Duchenne Muscular Dystrophy PRINCIPAL...Advanced Gene Therapy for Treatment of Cardiomyopathy and Respiratory Insufficiency in Duchenne Muscular Dystrophy 5a. CONTRACT NUMBER 5b. GRANT...effective recombinant AAV vector serotype 9 delivery system for the treatment of cardiorespiratory dysfunction in Duchenne Muscular Dystrophy . 2

  18. Relationship between metabolic cost and muscular coactivation across running speeds.

    PubMed

    Moore, Isabel S; Jones, Andrew M; Dixon, Sharon J

    2014-11-01

    Muscular coactivation can help stabilise a joint, but contrasting results in previous gait studies highlight that it is not clear whether this is metabolically beneficial. The aim was to assess the relationship between the metabolic cost of running and muscular coactivation across different running speeds, in addition to assessing the reliability and precision of lower limb muscular coactivation. Eleven female recreational runners visited the laboratory on two separate occasions. On both occasions subjects ran at three speeds (9.1, 11 and 12 km h(-1)) for six minutes each. Oxygen consumption and electromyographic data were simultaneously recorded during the final two minutes of each speed. Temporal coactivations of lower limb muscles during the stance phase were calculated. Five muscles were assessed: rectus femoris, vastus lateralis, biceps femoris, tibialis anterior and gastrocnemius lateralis. Nonparametric correlations revealed at least one significant, positive association between lower limb muscular coactivation and the metabolic cost of running for each speed. The length of tibialis anterior activation and muscular coactivation of the biceps femoris-tibialis anterior and gastrocnemius lateralis-tibialis anterior decreased with speed. These results show that longer coactivations of the proximal (rectus femoris-biceps femoris and vastus lateralis-biceps femoris) and leg extensor (rectus femoris-gastrocnemius lateralis) muscles were related to a greater metabolic cost of running, which could be detrimental to performance. The decrease in coactivation in the flexor and distal muscles at faster speeds occurs due to the shorter duration of tibialis anterior activation as speed increases, yet stability may be maintained. Copyright © 2013 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  19. Disparities in the diagnostic process of Duchenne and Becker muscular dystrophy.

    PubMed

    Holtzer, Caleb; Meaney, F John; Andrews, Jennifer; Ciafaloni, Emma; Fox, Deborah J; James, Katherine A; Lu, Zhenqiang; Miller, Lisa; Pandya, Shree; Ouyang, Lijing; Cunniff, Christopher

    2011-11-01

    To determine whether sociodemographic factors are associated with delays at specific steps in the diagnostic process of Duchenne and Becker muscular dystrophy. We examined abstracted medical records for 540 males from population-based surveillance sites in Arizona, Colorado, Georgia, Iowa, and western New York. We used linear regressions to model the association of three sociodemographic characteristics with age at initial medical evaluation, first creatine kinase measurement, and earliest DNA analysis while controlling for changes in the diagnostic process over time. The analytical dataset included 375 males with information on family history of Duchenne and Becker muscular dystrophy, neighborhood poverty levels, and race/ethnicity. Black and Hispanic race/ethnicity predicted older ages at initial evaluation, creatine kinase measurement, and DNA testing (P < 0.05). A positive family history of Duchenne and Becker muscular dystrophy predicted younger ages at initial evaluation, creatine kinase measurement and DNA testing (P < 0.001). Higher neighborhood poverty was associated with earlier ages of evaluation (P < 0.05). Racial and ethnic disparities in the diagnostic process for Duchenne and Becker muscular dystrophy are evident even after adjustment for family history of Duchenne and Becker muscular dystrophy and changes in the diagnostic process over time. Black and Hispanic children are initially evaluated at older ages than white children, and the gap widens at later steps in the diagnostic process.

  20. Intramuscular renin-angiotensin system is activated in human muscular dystrophy.

    PubMed

    Sun, Guilian; Haginoya, Kazuhiro; Dai, Hongmei; Chiba, Yoko; Uematsu, Mitsugu; Hino-Fukuyo, Naomi; Onuma, Akira; Iinuma, Kazuie; Tsuchiya, Shigeru

    2009-05-15

    To investigate the role of the muscular renin-angiotensin system (RAS) in human muscular dystrophy, we used immunohistochemistry and Western blotting to examine the cellular localization of angiotensin-converting enzyme (ACE), the angiotensin II type 1 receptor (AT1) and the angiotensin II type 2 receptor (AT2) in muscle biopsies from patients with Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), and congenital muscular dystrophy (CMD). In normal muscle, ACE was expressed in vascular endothelial cells and neuromuscular junctions (NMJs), whereas AT1 was immunolocalized to the smooth muscle cells of blood vessels and intramuscular nerve twigs. AT2 was immunolocalized in the smooth muscle cells of blood vessels. These findings suggest that the RAS has a functional role in peripheral nerves and NMJs. ACE and AT1, but AT2 immunoreactivity were increased markedly in dystrophic muscle as compared to controls. ACE and the AT1 were strongly expressed in the cytoplasm and nuclei of regenerating muscle fibers, fibroblasts, and in macrophages infiltrating necrotic fibers. Double immunolabeling revealed that activated fibroblasts in the endomysium and perimysium of DMD and CMD muscle were positive for ACE and AT1. Triple immunolabeling demonstrated that transforming growth factor-beta1 (TGF-beta1) and ACE were colocalized on the cytoplasm of activated fibroblasts in dystrophic muscle. Furthermore, Western blotting showed increases in the expression of AT1 and TGF-beta1 protein in dystrophic muscle, which coincided with our immunohistochemical results. The overexpression of ACE and AT1 in dystrophic muscle would likely result in the increased production of Ang II, which may act on these cells in an autocrine manner via AT1. The activation of AT1 may induce fibrous tissue formation through overexpression of TGF-beta1, which potently activates fibrogenesis and suppresses regeneration. In conclusion, our results imply that the intramuscular RAS-TGF-beta1 pathway

  1. Meeting the Assistive Technology Needs of Students with Duchenne Muscular Dystrophy

    ERIC Educational Resources Information Center

    Heller, Kathryn Wolff; Mezei, Peter J.; Avant, Mary Jane Thompson

    2009-01-01

    Students with Duchenne muscular dystrophy (DMD) have a degenerative disease that requires ongoing changes in assistive technology (AT). The AT team needs to be knowledgeable about the disease and its progression in order to meet these students' changing needs in a timely manner. The unique needs of students with Duchenne muscular dystrophy in…

  2. Investigation of Poor Academic Achievement in Children with Duchenne Muscular Dystrophy

    ERIC Educational Resources Information Center

    Hinton, V. J.; De Vivo, D. C.; Fee, R.; Goldstein, E.; Stern, Y.

    2004-01-01

    Duchenne Muscular Dystrophy (DMD) is a neurogenetic developmental disorder that presents with progressive muscular weakness. It is caused by a mutation in a gene that results in the absence of specific products that normally localize to muscle cells and the central nervous system (CNS). The majority of affected individuals have IQs within the…

  3. Unexpected death in elephantiasis due to an abnormal life-style.

    PubMed

    Sato, Hiroaki; Tanaka, Toshiko; Kasai, Kentaro; Kita, Toshiro; Tanaka, Noriyuki

    2009-11-01

    A 22-year-old man was found dead after he had continued to sit on a reclining chair for 2 years. He had consumed an unbalanced diet, kept wearing the same pair of socks and never washed himself for the term. His skin of bilateral crura developed into elephantiasis with severely festered ulcers on its surface. At autopsy, subcutaneous edema was significant in his lower limbs, and chronic circulatory disturbance of lymphoducts and veins was observed histologically. There were no crucial findings to account for chronic edema in the lower limbs. It has been reported that maintaining a seated posture obstructs both lymphoducts and veins because of bending the groin, decreases their return flow by inducing muscular atrophy, and causes subcutaneous edema in the lower limbs. Oligotrophia and dirt on his limbs might have exacerbated the chronic edema in elephantiasis. We concluded that a long-term abnormal life-style had caused fatal elephantiasis.

  4. Childhood cardiorespiratory fitness, muscular fitness and adult measures of glucose homeostasis.

    PubMed

    Fraser, Brooklyn J; Blizzard, Leigh; Schmidt, Michael D; Juonala, Markus; Dwyer, Terence; Venn, Alison J; Magnussen, Costan G

    2018-02-14

    To assess whether childhood cardiorespiratory fitness (CRF) and muscular fitness phenotypes (strength, power, endurance) predict adult glucose homeostasis measures. Prospective longitudinal study. Study examining participants who had physical fitness measured in childhood (aged 7-15 years) and who attended follow-up clinics approximately 20 years later and provided a fasting blood sample which was tested for glucose and insulin. Physical fitness measurements included muscular strength (right and left grip, shoulder flexion, shoulder and leg extension), power (standing long jump distance) and endurance (number of push-ups in 30s), and CRF (1.6km run duration). In adulthood, fasting glucose and insulin levels were used to derive glucose homeostasis measures of insulin resistance (HOMA2-IR) and beta cell function (HOMA2-β). A standard deviation increase in childhood CRF or muscular strength (males) was associated with fasting glucose (CRF: β=-0.06mmol/L), fasting insulin (CRF: β=-0.73mU/L; strength: β=-0.40mU/L), HOMA2-IR (CRF: β=-0.06; strength: β=-0.05) and HOMA2-β (CRF: β=-3.06%; strength: β=-2.62%) in adulthood, independent of the alternative fitness phenotype (all p<0.01). Adjustment for childhood waist circumference reduced the effect by 17-35% for CRF and 0-15% for muscular strength (males) and statistical significance remained for all associations expect between CRF, fasting glucose and HOMA2-β (p>0.06). CRF and muscular fitness in childhood were inversely associated with measures of fasting insulin, insulin resistance and beta cell function in adulthood. Childhood CRF and muscular fitness could both be potential independent targets for strategies to help reduce the development of adverse glucose homeostasis. Copyright © 2018 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  5. Dystrophin Immunity in Duchenne’s Muscular Dystrophy

    PubMed Central

    Mendell, Jerry R.; Campbell, Katherine; Rodino-Klapac, Louise; Sahenk, Zarife; Shilling, Chris; Lewis, Sarah; Bowles, Dawn; Gray, Steven; Li, Chengwen; Galloway, Gloria; Malik, Vinod; Coley, Brian; Clark, K. Reed; Li, Juan; Xiao, Xiao; Samulski, Jade; McPhee, Scott W.; Samulski, R. Jude; Walker, Christopher M.

    2010-01-01

    SUMMARY We report on delivery of a functional dystrophin transgene to skeletal muscle in six patients with Duchenne’s muscular dystrophy. Dystrophin-specific T cells were detected after treatment, providing evidence of transgene expression even when the functional protein was not visualized in skeletal muscle. Circulating dystrophin-specific T cells were unexpectedly detected in two patients before vector treatment. Revertant dystrophin fibers, which expressed functional, truncated dystrophin from the deleted endogenous gene after spontaneous in-frame splicing, contained epitopes targeted by the autoreactive T cells. The potential for T-cell immunity to self and nonself dystrophin epitopes should be considered in designing and monitoring experimental therapies for this disease. (Funded by the Muscular Dystrophy Association and others; ClinicalTrials.gov number, NCT00428935.) PMID:20925545

  6. Early-onset facioscapulohumeral muscular dystrophy type 1 with some atypical features.

    PubMed

    Dorobek, Małgorzata; van der Maarel, Silvère M; Lemmers, Richard J L F; Ryniewicz, Barbara; Kabzińska, Dagmara; Frants, Rune R; Gawel, Malgorzata; Walecki, Jerzy; Hausmanowa-Petrusewicz, Irena

    2015-04-01

    Facioscapulohumeral muscular dystrophy cases with facial weakness before the age of 5 and signs of shoulder weakness by the age of 10 are defined as early onset. Contraction of the D4Z4 repeat on chromosome 4q35 is causally related to facioscapulohumeral muscular dystrophy type 1, and the residual size of the D4Z4 repeat shows a roughly inverse correlation with the severity of the disease. Contraction of the D4Z4 repeat on chromosome 4q35 is believed to induce a local change in chromatin structure and consequent transcriptional deregulation of 4qter genes. We present early-onset cases in the Polish population that amounted to 21% of our total population with facioscapulohumeral muscular dystrophy. More than 27% of them presented with severe phenotypes (wheelchair dependency). The residual D4Z4 repeat sizes ranged from 1 to 4 units. In addition, even within early-onset facioscapulohumeral muscular dystrophy type 1 phenotypes, some cases had uncommon features (head drop, early disabling contractures, progressive ptosis, and respiratory insufficiency and cardiomyopathy). © The Author(s) 2014.

  7. Zebrafish models flex their muscles to shed light on muscular dystrophies.

    PubMed

    Berger, Joachim; Currie, Peter D

    2012-11-01

    Muscular dystrophies are a group of genetic disorders that specifically affect skeletal muscle and are characterized by progressive muscle degeneration and weakening. To develop therapies and treatments for these diseases, a better understanding of the molecular basis of muscular dystrophies is required. Thus, identification of causative genes mutated in specific disorders and the study of relevant animal models are imperative. Zebrafish genetic models of human muscle disorders often closely resemble disease pathogenesis, and the optical clarity of zebrafish embryos and larvae enables visualization of dynamic molecular processes in vivo. As an adjunct tool, morpholino studies provide insight into the molecular function of genes and allow rapid assessment of candidate genes for human muscular dystrophies. This unique set of attributes makes the zebrafish model system particularly valuable for the study of muscle diseases. This review discusses how recent research using zebrafish has shed light on the pathological basis of muscular dystrophies, with particular focus on the muscle cell membrane and the linkage between the myofibre cytoskeleton and the extracellular matrix.

  8. Rimmed vacuoles in Becker muscular dystrophy have similar features with inclusion myopathies.

    PubMed

    Momma, Kazunari; Noguchi, Satoru; Malicdan, May Christine V; Hayashi, Yukiko K; Minami, Narihiro; Kamakura, Keiko; Nonaka, Ikuya; Nishino, Ichizo

    2012-01-01

    Rimmed vacuoles in myofibers are thought to be due to the accumulation of autophagic vacuoles, and can be characteristic in certain myopathies with protein inclusions in myofibers. In this study, we performed a detailed clinical, molecular, and pathological characterization of Becker muscular dystrophy patients who have rimmed vacuoles in muscles. Among 65 Becker muscular dystrophy patients, we identified 12 patients who have rimmed vacuoles and 11 patients who have deletions in exons 45-48 in DMD gene. All patients having rimmed vacuoles showed milder clinical features compared to those without rimmed vacuoles. Interestingly, the rimmed vacuoles in Becker muscular dystrophy muscles seem to represent autophagic vacuoles and are also associated with polyubiquitinated protein aggregates. These findings support the notion that rimmed vacuoles can appear in Becker muscular dystrophy, and may be related to the chronic changes in muscle pathology induced by certain mutations in the DMD gene.

  9. Comparative study on the muscular load of the arms using hair driers.

    PubMed

    Harada, H; Katsuura, T; Kikuchi, Y

    1995-12-01

    The purpose of the present study was to evaluate the muscular load of the arm when combing the hair using different "kuru-kuru" type of hair driers. Ten female students (20-24 years old) volunteered as subjects. Five combing patterns were conducted as follows: 1) comb outer layer of right side of hair using right hand, 2) comb outer layer of left side of hair using right hand, 3) comb inner layer of left side of hair using right hand, 4) comb outer layer of back hair using right hand, and 5) comb inner layer of right side of hair using left hand. Surface EMGs were recorded from M. flexor carpi ulnaris, M. brachioradialis, M. biceps brachii, M. triceps brachii, M. deltoideus and M. trapezius of both sides of body. Integrated EMGs (iEMGs) were used to evaluate muscular load for each of the seven different types of hair driers used. The relationship between iEMGs and weight, center of gravity, diameter, length, and circumference of each hair drier were examined. The weight of hair driers tended to be the effective factor on the muscular load. Muscular load also had a tendency to be affected by the shape of the grips. With regard to the hand size, the longer the thumb length, the smaller is the muscular load. It was suggested that a relatively large diameter of the bulb-shaped grip of the drier gave a smaller muscular load among the hair driers examined in the present experiment.

  10. Serum creatinine level: a supplemental index to distinguish Duchenne muscular dystrophy from Becker muscular dystrophy.

    PubMed

    Zhang, Huili; Zhu, Yuling; Sun, Yiming; Liang, Yingyin; Li, Yaqin; Zhang, Yu; Deng, Langhui; Wen, Xingxuan; Zhang, Cheng

    2015-01-01

    To improve assessment of dystrophinopathy, the aim of this study was to identify whether serum creatinine (Crn) level reflects disease severity. Biochemical, Vignos score, and genetic data were collected on 212 boys with dystrophinopathy. Serum Crn level had a strong inverse correlation with Vignos score by simple correlation (r = -0.793) and partial correlation analysis after adjustment for age, height, and weight (r = -0.791; both P < 0.01). Serum Crn level was significantly higher in patients with in-frame than out-of-frame mutations (Z = -4.716,  P < 0.01) and in Becker muscular dystrophy (BMD) patients than Duchenne muscular dystrophy (DMD) patients at ages 4, 5, 7, and 9 yr (all P < 0.0125). After adjusting for age, height, and weight, BMD patients still had a significantly higher serum Crn level than DMD patients (β = 7.140,  t = 6.277,  P < 0.01). Serum Crn level reflected disease severity and may serve as a supplemental index to distinguish DMD from BMD in clinical practice.

  11. Effects of Partner's Improvisational Resistance Training on dancers' muscular strength.

    PubMed

    Vetter, Rheba E; Dorgo, Sandor

    2009-05-01

    The purpose of this study was to observe the effects of Partner's Improvisational Resistance Training (PIRT) on muscular strength, body circumference, and body fat percentage in 10 female college-age dancers in comparison with 8 female dancers in a control group. The PIRT program, based on the concepts of manual resistance training, is the application of contact improvisation in a systematic strength development program, which proposes a way of contextualizing muscular strength development within the dance class. The program lasted 8 weeks, meeting 3 times weekly for 60-minute sessions. The muscular strength pre- and posttests included 1-repetition maximum (1RM) for leg extension, leg flexion, leg press, bench press, lat pulldown, back extension, and modified sit-up. Hydrostatic weighing for body composition and circumference measures on the waist, hip, shoulder, upper arm, and thigh were made pre- and posttest analyses. There were no significant pretest differences between the groups for age, height, body weight, body fat percentage, any of the circumference measures, or 5 of the 7 muscular strength measures. At posttest, neither group showed significant changes in total body weight, body fat percentage, or lean body weight. The experimental group showed significant decrements in the waist and hip circumference measures, and all other body circumference changes were nonsignificant. The experimental group showed significant changes from pretest to posttest for all seven 1RM strength measures and greater absolute and relative strength improvements in 5 measures compared with the control group. Thus, the 8-week PIRT program for female dancers was found effective in improving overall muscular strength and decreasing circumference in the waist-hip region, but it did not elicit significant changes in body composition.

  12. [Motor function evaluation in merosin-deficient congenital muscular dystrophy children].

    PubMed

    Rocco, Fernanda M; Luz, Fernanda H Gianini; Rossato, Alexsander Junquera; Fernandes, Antônio Carlos; Oliveira, Acary S B; Betetas, Javier Toledano; Zanoteli, Edmar

    2005-06-01

    Congenital muscular dystrophy (CMD) is a heterogeneous group of disorders characterized by early onset of hypotonia and weakness. Almost 50% of the cases are caused by primary deficiency of a protein named merosin (MD), and present a homogenous phenotype with a severe motor and respiratory involvement. Eleven children with clinical and histological diagnosis of CMD-MD, aged of 3 to 15 years, were studied using the manual muscle testing (Medical Research Council), goniometric analysis, motor ability and day life activities (Barthel index) scales, with the objective to characterize the main motor function limitations. The muscular groups most affected were cervical flexors, paravertebral and proximal portions of limbs. The muscular groups of upper limbs were as affected as the lower limbs, and the extensors were more affected than the flexors groups. All children had severe muscular retractions on the hip, knee and elbow. Other frequent deformities were scoliosis and equinus-varum feet. No children presented the motor ability to walk, stand up and crawl; and all of them were classified as dependents or semi-dependents in the day life activities scale. Our findings confirm the severe and diffuse involvement of skeletal muscle in CMD-MD patients, producing serious motor limitations and deformities.

  13. Clinical and genetic diversity of SMN1-negative proximal spinal muscular atrophies

    PubMed Central

    Jordanova, Albena

    2014-01-01

    Hereditary spinal muscular atrophy is a motor neuron disorder characterized by muscle weakness and atrophy due to degeneration of the anterior horn cells of the spinal cord. Initially, the disease was considered purely as an autosomal recessive condition caused by loss-of-function SMN1 mutations on 5q13. Recent developments in next generation sequencing technologies, however, have unveiled a growing number of clinical conditions designated as non-5q forms of spinal muscular atrophy. At present, 16 different genes and one unresolved locus are associated with proximal non-5q forms, having high phenotypic variability and diverse inheritance patterns. This review provides an overview of the current knowledge regarding the phenotypes, causative genes, and disease mechanisms associated with proximal SMN1-negative spinal muscular atrophies. We describe the molecular and cellular functions enriched among causative genes, and discuss the challenges in the post-genomics era of spinal muscular atrophy research. PMID:24970098

  14. Muscle-Derived Proteins as Serum Biomarkers for Monitoring Disease Progression in Three Forms of Muscular Dystrophy

    PubMed Central

    Burch, Peter M.; Pogoryelova, Oksana; Goldstein, Richard; Bennett, Donald; Guglieri, Michela; Straub, Volker; Bushby, Kate; Lochmüller, Hanns; Morris, Carl

    2015-01-01

    Abstract Background: Identifying translatable, non-invasive biomarkers of muscular dystrophy that better reflect the disease pathology than those currently available would aid the development of new therapies, the monitoring of disease progression and the response to therapy. Objective: The goal of this study was to evaluate a panel of serum protein biomarkers with the potential to specifically detect skeletal muscle injury. Method: Serum concentrations of skeletal troponin I (sTnI), myosin light chain 3 (Myl3), fatty acid binding protein 3 (FABP3) and muscle-type creatine kinase (CKM) proteins were measured in 74 Duchenne muscular dystrophy (DMD), 38 Becker muscular dystrophy (BMD) and 49 Limb-girdle muscular dystrophy type 2B (LGMD2B) patients and 32 healthy controls. Results: All four proteins were significantly elevated in the serum of these three muscular dystrophy patient populations when compared to healthy controls, but, interestingly, displayed different profiles depending on the type of muscular dystrophy. Additionally, the effects of patient age, ambulatory status, cardiac function and treatment status on the serum concentrations of the proteins were investigated. Statistical analysis revealed correlations between the serum concentrations and certain clinical endpoints including forced vital capacity in DMD patients and the time to walk ten meters in LGMD2B patients. Serum concentrations of these proteins were also elevated in two preclinical models of muscular dystrophy, the mdx mouse and the golden-retriever muscular dystrophy dog. Conclusions: These proteins, therefore, are potential muscular dystrophy biomarkers for monitoring disease progression and therapeutic response in both preclinical and clinical studies. PMID:26870665

  15. Genetics Home Reference: Fukuyama congenital muscular dystrophy

    MedlinePlus

    ... Fujii T, Aiba H, Toda T. Seizure-genotype relationship in Fukuyama-type congenital muscular dystrophy. Brain Dev. ... for Links Data Files & API Site Map Subscribe Customer Support USA.gov Copyright Privacy Accessibility FOIA Viewers & ...

  16. [Current status and future prospects of research on Fukuyama muscular dystrophy].

    PubMed

    Toda, Tatsushi

    2015-08-01

    Fukuyama congenital muscular dystrophy(FCMD) is a second common childhood muscular dystrophy in Japan. All FCMD patients have ancestral insertion of the SVA retrotransposal element into fukutin. We show that aberrant mRNA splicing induced by SVA exon-trapping caused FCMD. Introduction of 3 cocktailed antisense oligonucleotides(AONs) targeting around these splice sites prevented pathogenic splicing in FCMD patient cells and model mice, and normalized protein production and functions of Fukutin as well as O-glycosylation of α-dystroglycan. We show the promise of splicing modulation therapy as the first radical clinical treatment for FCMD in the near future. We also show that fukutin is prerequisite to ameliorate muscular dystrophic phenotype by myofiber-selective LARGE expression. Recent advances in FCMD are discussed.

  17. Effects of Passive Physical Exercise on Peripheral Vision in Muscular Dystrophic Children.

    ERIC Educational Resources Information Center

    Eickelberg, Warren; And Others

    1983-01-01

    The effects of passive exercise of the extremities on peripheral vision of muscular dystrophic children aged 9 to 13 years was investigated. Compared to control subjects, those who experienced six minutes of passive exercise evidenced increased peripheral vision. Curriculum revisions for muscular dystrophic children indicate the importance of…

  18. Maximalist vs. minimalist shoes: dose-effect response of elastic compression on muscular oscillations.

    PubMed

    Gellaerts, Jules; Pirard, Maxime; Muzic, Jessie; Peseux, Maxime; Ménétrier, Arnaud

    2017-10-01

    The aim of this study was to establish whether maximalist shoes engender fewer muscular oscillations than minimalist shoes and determine to what extent these shoes, when combined with elastic compression (EC), help reduce muscle oscillations. For that purpose, we tested the effects of various levels of compression on the muscular oscillations in maximalist and minimalist footwear. Eleven volunteers executed 16 one-minute passages on a flat treadmill in a randomized order: maximalists or minimalists, walking (6 km/h) or running (10 km/h), without EC (control condition [CON]) or with EC applying different pressures (9.6 mmHg, 14.5 mmHg and 20.4 mmHg). The muscular oscillations were measured on both thighs, on the rectus femoris and on the vastus medialis with tri-axial accelerometers. Muscular oscillations are lower in maximalist shoes than in minimalist shoes, for both walking to 6 km/h and running to 10 km/h (P<0.05). Oscillations are also reduced with EC (P<0.05). This decrease is most marked when the pressure exercised by the EC is increased. Increased compression with minimalist shoes reduces muscular oscillations as much as maximalist shoes, when combined with lower compression.

  19. Impact of a supervised worksite exercise program on back and core muscular endurance in firefighters.

    PubMed

    Mayer, John M; Quillen, William S; Verna, Joe L; Chen, Ren; Lunseth, Paul; Dagenais, Simon

    2015-01-01

    Low back pain is a leading cause of disability in firefighters and is related to poor muscular endurance. This study examined the impact of supervised worksite exercise on back and core muscular endurance in firefighters. A cluster randomized controlled trial was used for this study. The study occurred in fire stations of a municipal fire department (Tampa, Florida). Subjects were 96 full-duty career firefighters who were randomly assigned by fire station to exercise (n = 54) or control (n = 42) groups. Exercise group participants completed a supervised exercise targeting the back and core muscles while on duty, two times per week for 24 weeks, in addition to their usual fitness regimen. Control group participants continued their usual fitness regimen. Back and core muscular endurance was assessed with the Biering-Sorensen test and plank test, respectively. Changes in back and core muscular endurance from baseline to 24 weeks were compared between groups using analysis of covariance and linear mixed effects models. After 24 weeks, the exercise group had 12% greater (p = .021) back muscular endurance and 21% greater (p = .0006) core muscular endurance than did the control group. The exercise intervention did not disrupt operations or job performance. A supervised worksite exercise program was safe and effective in improving back and core muscular endurance in firefighters, which could protect against future low back pain.

  20. The Relationship between Selected Body Composition Variables and Muscular Endurance in Women

    ERIC Educational Resources Information Center

    Esco, Michael R.; Olson, Michele S.; Williford, Henry N.

    2010-01-01

    The primary purpose of this study was to determine if muscular endurance is affected by referenced waist circumference groupings, independent of body mass and subcutaneous abdominal fat, in women. This study also explored whether selected body composition measures were associated with muscular endurance. Eighty-four women were measured for height,…

  1. Kinematics, muscular activity and propulsion in gopher snakes

    PubMed

    Moon; Gans

    1998-10-01

    Previous studies have addressed the physical principles and muscular activity patterns underlying terrestrial lateral undulation in snakes, but not the mechanism by which muscular activity produces curvature and propulsion. In this study, we used synchronized electromyography and videography to examine the muscular basis and propulsive mechanism of terrestrial lateral undulation in gopher snakes Pituophis melanoleucus affinis. Specifically, we used patch electrodes to record from the semispinalis, longissimus dorsi and iliocostalis muscles in snakes pushing against one or more pegs. Axial bends propagate posteriorly along the body and contact the pegs at or immediately posterior to an inflection of curvature, which then reverses anterior to the peg. The vertebral column bends broadly around a peg, whereas the body wall bends sharply and asymmetrically around the anterior surface of the peg. The epaxial muscles are always active contralateral to the point of contact with a peg; they are activated slightly before or at the point of maximal convexity and deactivated variably between the inflection point and the point of maximal concavity. This pattern is consistent with muscular shortening and the production of axial bends, although variability in the pattern indicates that other muscles may affect the mechanics of the epaxial muscles. The kinematic and motor patterns in snakes crawling against experimentally increased drag indicated that forces are produced largely by muscles that are active in the axial bend around each peg, rather than by distant muscles from which the forces might be transmitted by connective tissues. At each point of force exertion, the propulsive mechanism of terrestrial lateral undulation may be modeled as a type of cam-follower, in which continuous bending of the trunk around the peg produces translation of the snake.

  2. Repair of an inguinoscrotal hernia in a patient with Becker muscular dystrophy.

    PubMed

    Tatulli, F; Caraglia, A; Delcuratolo, A; Cassano, S; Chetta, G S

    2017-01-01

    Inguinal hernia repairs are routinely performed as outpatient procedures in most patients, whereas a few require admission due to clinical or social peculiarities. Muscular dystrophies are inherited disorders characterized by progressive muscle wasting and weakness. In case of surgery there is no definite recommendation for either general or regional anesthesia. This contribution regards a 48 y. o. male patient diagnosed with Becker Muscular Dystrophy by muscle biopsy 10 years earlier. He had a left-sided sizable inguinoscrotal hernia with repeat episodes of incarceration. An elective mesh repair with suction drainage was accomplished under selective spinal anesthesia. The post-operative course was uneventful. A few inguinal hernia repairs require admission due to peculiarities such as extensive scrotal hernias requiring suction drainage. Muscular dystrophies are inherited disorders with no cure and no two dystrophy patients are exactly alike, therefore the health issues will be different for each individual. In case of surgery there is no definite recommendation for either general or regional anesthesia. This contribution regards the successful elective mesh repair with suction drainage of a large left-sided inguino-scrotal hernia in a 48 y. o. male patient affected by Becker muscular dystrophy by selective spinal anesthesia obtained by 10 milligrams of hyperbaric bupivacaine. Effective mesh repair with suction drainage of large inguinal hernias under spinal anesthesia can be achieved in patients affected by muscular dystrophy.

  3. Nanolipodendrosome-loaded glatiramer acetate and myogenic differentiation 1 as augmentation therapeutic strategy approaches in muscular dystrophy.

    PubMed

    Afzal, Ehsan; Zakeri, Saba; Keyhanvar, Peyman; Bagheri, Meisam; Mahjoubi, Parvin; Asadian, Mahtab; Omoomi, Nogol; Dehqanian, Mohammad; Ghalandarlaki, Negar; Darvishmohammadi, Tahmineh; Farjadian, Fatemeh; Golvajoee, Mohammad Sadegh; Afzal, Shadi; Ghaffari, Maryam; Cohan, Reza Ahangari; Gravand, Amin; Ardestani, Mehdi Shafiee

    2013-01-01

    [Corrected] Muscular dystrophies consist of a number of juvenile and adult forms of complex disorders which generally cause weakness or efficiency defects affecting skeletal muscles or, in some kinds, other types of tissues in all parts of the body are vastly affected. In previous studies, it was observed that along with muscular dystrophy, immune inflammation was caused by inflammatory cells invasion - like T lymphocyte markers (CD8+/CD4+). Inflammatory processes play a major part in muscular fibrosis in muscular dystrophy patients. Additionally, a significant decrease in amounts of two myogenic recovery factors (myogenic differentation 1 [MyoD] and myogenin) in animal models was observed. The drug glatiramer acetate causes anti-inflammatory cytokines to increase and T helper (Th) cells to induce, in an as yet unknown mechanism. MyoD recovery activity in muscular cells justifies using it alongside this drug. In this study, a nanolipodendrosome carrier as a drug delivery system was designed. The purpose of the system was to maximize the delivery and efficiency of the two drug factors, MyoD and myogenin, and introduce them as novel therapeutic agents in muscular dystrophy phenotypic mice. The generation of new muscular cells was analyzed in SW1 mice. Then, immune system changes and probable side effects after injecting the nanodrug formulations were investigated. The loaded lipodendrimer nanocarrier with the candidate drug, in comparison with the nandrolone control drug, caused a significant increase in muscular mass, a reduction in CD4+/CD8+ inflammation markers, and no significant toxicity was observed. The results support the hypothesis that the nanolipodendrimer containing the two candidate drugs will probably be an efficient means to ameliorate muscular degeneration, and warrants further investigation.

  4. Advances in genetic therapeutic strategies for Duchenne muscular dystrophy.

    PubMed

    Guiraud, Simon; Chen, Huijia; Burns, David T; Davies, Kay E

    2015-12-01

    What is the topic of this review? This review highlights recent progress in genetically based therapies targeting the primary defect of Duchenne muscular dystrophy. What advances does it highlight? Over the last two decades, considerable progress has been made in understanding the mechanisms underlying Duchenne muscular dystrophy, leading to the development of genetic therapies. These include manipulation of the expression of the gene or related genes, the splicing of the gene and its translation, and replacement of the gene using viral approaches. Duchenne muscular dystrophy is a lethal X-linked disorder caused by mutations in the dystrophin gene. In the absence of the dystrophin protein, the link between the cytoskeleton and extracellular matrix is destroyed, and this severely compromises the strength, flexibility and stability of muscle fibres. The devastating consequence is progressive muscle wasting and premature death in Duchenne muscular dystrophy patients. There is currently no cure, and despite exhaustive palliative care, patients are restricted to a wheelchair by the age of 12 years and usually succumb to cardiac or respiratory complications in their late 20s. This review provides an update on the current genetically based therapies and clinical trials that target or compensate for the primary defect of this disease. These include dystrophin gene-replacement strategies, genetic modification techniques to restore dystrophin expression, and modulation of the dystrophin homologue, utrophin, as a surrogate to re-establish muscle function. © 2015 The Authors. Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.

  5. Early functional impairment of sensory-motor connectivity in a mouse model of spinal muscular atrophy

    PubMed Central

    Mentis, George Z.; Blivis, Dvir; Liu, Wenfang; Drobac, Estelle; Crowder, Melissa E.; Kong, Lingling; Alvarez, Francisco J.; Sumner, Charlotte J.; O'Donovan, Michael J.

    2011-01-01

    SUMMARY To define alterations of neuronal connectivity that occur during motor neuron degeneration, we characterized the function and structure of spinal circuitry in spinal muscular atrophy (SMA) model mice. SMA motor neurons show reduced proprioceptive reflexes that correlate with decreased number and function of synapses on motor neuron somata and proximal dendrites. These abnormalities occur at an early stage of disease in motor neurons innervating proximal hindlimb muscles and medial motor neurons innervating axial muscles, but only at end-stage disease in motor neurons innervating distal hindlimb muscles. Motor neuron loss follows afferent synapse loss with the same temporal and topographical pattern. Trichostatin A, which improves motor behavior and survival of SMA mice, partially restores spinal reflexes illustrating the reversibility of these synaptic defects. De-afferentation of motor neurons is an early event in SMA and may be a primary cause of motor dysfunction that is amenable to therapeutic intervention. PMID:21315257

  6. Comparative proteomic profiling of soleus, extensor digitorum longus, flexor digitorum brevis and interosseus muscles from the mdx mouse model of Duchenne muscular dystrophy.

    PubMed

    Carberry, Steven; Brinkmeier, Heinrich; Zhang, Yaxin; Winkler, Claudia K; Ohlendieck, Kay

    2013-09-01

    Duchenne muscular dystrophy is due to genetic abnormalities in the dystrophin gene and represents one of the most frequent genetic childhood diseases. In the X-linked muscular dystrophy (mdx) mouse model of dystrophinopathy, different subtypes of skeletal muscles are affected to a varying degree albeit the same single base substitution within exon 23 of the dystrophin gene. Thus, to determine potential muscle subtype-specific differences in secondary alterations due to a deficiency in dystrophin, in this study, we carried out a comparative histological and proteomic survey of mdx muscles. We intentionally included the skeletal muscles that are often used for studying the pathomechanism of muscular dystrophy. Histological examinations revealed a significantly higher degree of central nucleation in the soleus and extensor digitorum longus muscles compared with the flexor digitorum brevis and interosseus muscles. Muscular hypertrophy of 20-25% was likewise only observed in the soleus and extensor digitorum longus muscles from mdx mice, but not in the flexor digitorum brevis and interosseus muscles. For proteomic analysis, muscle protein extracts were separated by fluorescence two-dimensional (2D) gel electrophoresis. Proteins with a significant change in their expression were identified by mass spectrometry. Proteomic profiling established an altered abundance of 24, 17, 19 and 5 protein species in the dystrophin-deficient soleus, extensor digitorum longus, flexor digitorum brevis and interosseus muscle, respectively. The key proteomic findings were verified by immunoblot analysis. The identified proteins are involved in the contraction-relaxation cycle, metabolite transport, muscle metabolism and the cellular stress response. Thus, histological and proteomic profiling of muscle subtypes from mdx mice indicated that distinct skeletal muscles are differentially affected by the loss of the membrane cytoskeletal protein, dystrophin. Varying degrees of perturbed protein

  7. Comparative proteomic profiling of soleus, extensor digitorum longus, flexor digitorum brevis and interosseus muscles from the mdx mouse model of Duchenne muscular dystrophy

    PubMed Central

    CARBERRY, STEVEN; BRINKMEIER, HEINRICH; ZHANG, YAXIN; WINKLER, CLAUDIA K.; OHLENDIECK, KAY

    2013-01-01

    Duchenne muscular dystrophy is due to genetic abnormalities in the dystrophin gene and represents one of the most frequent genetic childhood diseases. In the X-linked muscular dystrophy (mdx) mouse model of dystrophinopathy, different subtypes of skeletal muscles are affected to a varying degree albeit the same single base substitution within exon 23 of the dystrophin gene. Thus, to determine potential muscle subtype-specific differences in secondary alterations due to a deficiency in dystrophin, in this study, we carried out a comparative histological and proteomic survey of mdx muscles. We intentionally included the skeletal muscles that are often used for studying the pathomechanism of muscular dystrophy. Histological examinations revealed a significantly higher degree of central nucleation in the soleus and extensor digitorum longus muscles compared with the flexor digitorum brevis and interosseus muscles. Muscular hypertrophy of 20–25% was likewise only observed in the soleus and extensor digitorum longus muscles from mdx mice, but not in the flexor digitorum brevis and interosseus muscles. For proteomic analysis, muscle protein extracts were separated by fluorescence two-dimensional (2D) gel electrophoresis. Proteins with a significant change in their expression were identified by mass spectrometry. Proteomic profiling established an altered abundance of 24, 17, 19 and 5 protein species in the dystrophin-deficient soleus, extensor digitorum longus, flexor digitorum brevis and interosseus muscle, respectively. The key proteomic findings were verified by immunoblot analysis. The identified proteins are involved in the contraction-relaxation cycle, metabolite transport, muscle metabolism and the cellular stress response. Thus, histological and proteomic profiling of muscle subtypes from mdx mice indicated that distinct skeletal muscles are differentially affected by the loss of the membrane cytoskeletal protein, dystrophin. Varying degrees of perturbed protein

  8. Influence of Manual Labor at Work on Muscular Fitness and Its Relationship With Work Performance.

    PubMed

    Ryan, Eric D; Thompson, Brennan J; Sobolewski, Eric J

    2016-10-01

    The present study examined the influence of workplace manual labor on measures of muscular fitness, with a secondary aim to investigate the relationship between muscular fitness and work performance in blue-collar (BC) workers. Leg extension isokinetic strength at slow and fast velocities, hamstring and hip-flexor flexibility, and low back muscular endurance were examined in young and older BC workers and white-collar (WC) controls, while work performance was examined in the BC cohort. There were no differences in muscular fitness variables between BC and WC groups; however, the older men had lower low back muscular endurance (-43.0%) and strength at slow (-9.4%) and fast (-12.7%) velocities. Work performance was associated with strength at fast velocities (r = 0.633) in the older BC workers. Leg strength may influence work performance, with higher velocities becoming more important in older workers.

  9. Emerging genetic therapies to treat Duchenne muscular dystrophy

    PubMed Central

    Nelson, Stanley F.; Crosbie, Rachelle H.; Miceli, M. Carrie; Spencer, Melissa J.

    2010-01-01

    Purpose of review Duchenne muscular dystrophy is a progressive muscle degenerative disease caused by dystrophin mutations. The purpose of this review is to highlight two emerging therapies designed to repair the primary genetic defect, called `exon skipping' and `nonsense codon suppression'. Recent findings A drug, PTC124, was identified that suppresses nonsense codon translation termination. PTC124 can lead to restoration of some dystrophin expression in human Duchenne muscular dystrophy muscles with mutations resulting in premature stops. Two drugs developed for exon skipping, PRO051 and AVI-4658, result in the exclusion of exon 51 from mature mRNA. They can restore the translational reading frame to dystrophin transcripts from patients with a particular subset of dystrophin gene deletions and lead to some restoration of dystrophin expression in affected boys' muscle in vivo. Both approaches have concluded phase I trials with no serious adverse events. Summary These novel therapies that act to correct the primary genetic defect of dystrophin deficiency are among the first generation of therapies tailored to correct specific mutations in humans. Thus, they represent paradigm forming approaches to personalized medicine with the potential to lead to life changing treatment for those affected by Duchenne muscular dystrophy. PMID:19745732

  10. Clinical and genetic characterisation of dystrophin-deficient muscular dystrophy in a family of Miniature Poodle dogs.

    PubMed

    Sánchez, Lluís; Beltrán, Elsa; de Stefani, Alberta; Guo, Ling T; Shea, Anita; Shelton, G Diane; De Risio, Luisa; Burmeister, Louise M

    2018-01-01

    Four full-sibling intact male Miniature Poodles were evaluated at 4-19 months of age. One was clinically normal and three were affected. All affected dogs were reluctant to exercise and had generalised muscle atrophy, a stiff gait and a markedly elevated serum creatine kinase activity. Two affected dogs also showed poor development, learning difficulties and episodes of abnormal behaviour. In these two dogs, investigations into forebrain structural and metabolic diseases were unremarkable; electromyography demonstrated fibrillation potentials and complex repetitive discharges in the infraspinatus, supraspinatus and epaxial muscles. Histopathological, immunohistochemical and immunoblotting analyses of muscle biopsies were consistent with dystrophin-deficient muscular dystrophy. DNA samples were obtained from all four full-sibling male Poodles, a healthy female littermate and the dam, which was clinically normal. Whole genome sequencing of one affected dog revealed a >5 Mb deletion on the X chromosome, encompassing the entire DMD gene. The exact deletion breakpoints could not be experimentally ascertained, but we confirmed that this region was deleted in all affected males, but not in the unaffected dogs. Quantitative polymerase chain reaction confirmed all three affected males were hemizygous for the mutant X chromosome, while the wildtype chromosome was observed in the unaffected male littermate. The female littermate and the dam were both heterozygous for the mutant chromosome. Forty-four Miniature Poodles from the general population were screened for the mutation and were homozygous for the wildtype chromosome. The finding represents a naturally-occurring mutation causing dystrophin-deficient muscular dystrophy in the dog.

  11. Clinical and genetic characterisation of dystrophin-deficient muscular dystrophy in a family of Miniature Poodle dogs

    PubMed Central

    Beltrán, Elsa; de Stefani, Alberta; Guo, Ling T.; Shea, Anita; Shelton, G. Diane

    2018-01-01

    Four full-sibling intact male Miniature Poodles were evaluated at 4–19 months of age. One was clinically normal and three were affected. All affected dogs were reluctant to exercise and had generalised muscle atrophy, a stiff gait and a markedly elevated serum creatine kinase activity. Two affected dogs also showed poor development, learning difficulties and episodes of abnormal behaviour. In these two dogs, investigations into forebrain structural and metabolic diseases were unremarkable; electromyography demonstrated fibrillation potentials and complex repetitive discharges in the infraspinatus, supraspinatus and epaxial muscles. Histopathological, immunohistochemical and immunoblotting analyses of muscle biopsies were consistent with dystrophin-deficient muscular dystrophy. DNA samples were obtained from all four full-sibling male Poodles, a healthy female littermate and the dam, which was clinically normal. Whole genome sequencing of one affected dog revealed a >5 Mb deletion on the X chromosome, encompassing the entire DMD gene. The exact deletion breakpoints could not be experimentally ascertained, but we confirmed that this region was deleted in all affected males, but not in the unaffected dogs. Quantitative polymerase chain reaction confirmed all three affected males were hemizygous for the mutant X chromosome, while the wildtype chromosome was observed in the unaffected male littermate. The female littermate and the dam were both heterozygous for the mutant chromosome. Forty-four Miniature Poodles from the general population were screened for the mutation and were homozygous for the wildtype chromosome. The finding represents a naturally-occurring mutation causing dystrophin-deficient muscular dystrophy in the dog. PMID:29474464

  12. Muscle MRI findings in facioscapulohumeral muscular dystrophy.

    PubMed

    Gerevini, Simonetta; Scarlato, Marina; Maggi, Lorenzo; Cava, Mariangela; Caliendo, Giandomenico; Pasanisi, Barbara; Falini, Andrea; Previtali, Stefano Carlo; Morandi, Lucia

    2016-03-01

    Facioscapulohumeral muscular dystrophy (FSHD) is characterized by extremely variable degrees of facial, scapular and lower limb muscle involvement. Clinical and genetic determination can be difficult, as molecular analysis is not always definitive, and other similar muscle disorders may have overlapping clinical manifestations. Whole-body muscle MRI examination for fat infiltration, atrophy and oedema was performed to identify specific patterns of muscle involvement in FSHD patients (30 subjects), and compared to a group of control patients (23) affected by other myopathies (NFSHD). In FSHD patients, we detected a specific pattern of muscle fatty replacement and atrophy, particularly in upper girdle muscles. The most frequently affected muscles, including paucisymptomatic and severely affected FSHD patients, were trapezius, teres major and serratus anterior. Moreover, asymmetric muscle involvement was significantly higher in FSHD as compared to NFSHD patients. In conclusion, muscle MRI is very sensitive for identifying a specific pattern of involvement in FSHD patients and in detecting selective muscle involvement of non-clinically testable muscles. Muscle MRI constitutes a reliable tool for differentiating FSHD from other muscular dystrophies to direct diagnostic molecular analysis, as well as to investigate FSHD natural history and follow-up of the disease. Muscle MRI identifies a specific pattern of muscle involvement in FSHD patients. Muscle MRI may predict FSHD in asymptomatic and severely affected patients. Muscle MRI of upper girdle better predicts FSHD. Muscle MRI may differentiate FSHD from other forms of muscular dystrophy. Muscle MRI may show the involvement of non-clinical testable muscles.

  13. Correlations of frontal lip-line canting with craniofacial morphology and muscular activity.

    PubMed

    Cho, Jin-Hyoung; Kim, Eun-Jung; Kim, Byeong-Chae; Cho, Ki-Hyun; Lee, Ki-Heon; Hwang, Hyeon-Shik

    2007-09-01

    The purpose of this study was to investigate factors affecting lip-line canting by using musculoskeletal analyses. Fifty-six adults with lip-line canting were selected as subjects. They were divided into 3 groups according to the changes of lip line during smiling: increasing (group I), decreasing (group D), and minimal (group M). Lip-line canting at rest was correlated to craniofacial morphology and muscular activity: Regarding craniofacial morphology, various craniofacial measurements in lateral and frontal cephalograms were used, including inclination of the tongue blade placed across both first molars. The zygomaticus major was the focus of the measurement of muscular activity affecting lip-line canting, and its activity during smiling was evaluated by using a needle electrode. In group I, lip-line canting at rest showed a significant correlation with the right-left (R/L) difference of muscular activity, but no significant correlation with the measurements of craniofacial morphology. In group D, lip-line canting showed a positive correlation with the measurements of craniofacial morphology, such as the inclination of the tongue blade, and a negative correlation with the R/L difference of muscular activity. In group M, lip-line canting showed no significant correlation with the R/L difference of muscular activity, but a significant correlation with inclination of the tongue blade. The results indicate that lip-line canting is caused by craniofacial morphology when the change of lip-line canting during smiling is minimal, whereas lip-line canting is affected by the R/L difference of muscular activity in addition to craniofacial morphology when the cant of lip line markedly changes during smiling. The findings suggest that the cause of lip-line canting can be identified easily by the change of canting during smiling, without complicated musculoskeletal analyses.

  14. Fat embolism after fractures in Duchenne muscular dystrophy: an underdiagnosed complication? A systematic review.

    PubMed

    Feder, David; Koch, Miriam Eva; Palmieri, Beniamino; Fonseca, Fernando Luiz Affonso; Carvalho, Alzira Alves de Siqueira

    2017-01-01

    Duchenne muscular dystrophy is the most frequent lethal genetic disease. Several clinical trials have established both the beneficial effect of steroids in Duchenne muscular dystrophy and the well-known risk of side effects associated with their daily use. For many years it has been known that steroids associated with ambulation loss lead to obesity and also damage the bone structure resulting in the bone density reduction and increased incidence of bone fractures and fat embolism syndrome, an underdiagnosed complication after fractures. Fat embolism syndrome is characterized by consciousness disturbance, respiratory failure and skin rashes. The use of steroids in Duchenne muscular dystrophy may result in vertebral fractures, even without previous trauma. Approximately 25% of patients with Duchenne muscular dystrophy have a long bone fracture, and 1% to 22% of fractures have a chance to develop fat embolism syndrome. As the patients with Duchenne muscular dystrophy have progressive cardiac and respiratory muscle dysfunction, the fat embolism may be unnoticed clinically and may result in increased risk of death and major complications. Different treatments and prevention measures of fat embolism have been proposed; however, so far, there is no efficient therapy. The prevention, early diagnosis and adequate symptomatic treatment are of paramount importance. The fat embolism syndrome should always be considered in patients with Duchenne muscular dystrophy presenting with fractures, or an unexplained and sudden worsening of respiratory and cardiac symptoms.

  15. Fat embolism after fractures in Duchenne muscular dystrophy: an underdiagnosed complication? A systematic review

    PubMed Central

    Feder, David; Koch, Miriam Eva; Palmieri, Beniamino; Fonseca, Fernando Luiz Affonso; Carvalho, Alzira Alves de Siqueira

    2017-01-01

    Duchenne muscular dystrophy is the most frequent lethal genetic disease. Several clinical trials have established both the beneficial effect of steroids in Duchenne muscular dystrophy and the well-known risk of side effects associated with their daily use. For many years it has been known that steroids associated with ambulation loss lead to obesity and also damage the bone structure resulting in the bone density reduction and increased incidence of bone fractures and fat embolism syndrome, an underdiagnosed complication after fractures. Fat embolism syndrome is characterized by consciousness disturbance, respiratory failure and skin rashes. The use of steroids in Duchenne muscular dystrophy may result in vertebral fractures, even without previous trauma. Approximately 25% of patients with Duchenne muscular dystrophy have a long bone fracture, and 1% to 22% of fractures have a chance to develop fat embolism syndrome. As the patients with Duchenne muscular dystrophy have progressive cardiac and respiratory muscle dysfunction, the fat embolism may be unnoticed clinically and may result in increased risk of death and major complications. Different treatments and prevention measures of fat embolism have been proposed; however, so far, there is no efficient therapy. The prevention, early diagnosis and adequate symptomatic treatment are of paramount importance. The fat embolism syndrome should always be considered in patients with Duchenne muscular dystrophy presenting with fractures, or an unexplained and sudden worsening of respiratory and cardiac symptoms. PMID:29066903

  16. Abnormal Structure–Function Relationship in Spasmodic Dysphonia

    PubMed Central

    Ludlow, Christy L.

    2012-01-01

    Spasmodic dysphonia (SD) is a primary focal dystonia characterized by involuntary spasms in the laryngeal muscles during speech production. Although recent studies have found abnormal brain function and white matter organization in SD, the extent of gray matter alterations, their structure–function relationships, and correlations with symptoms remain unknown. We compared gray matter volume (GMV) and cortical thickness (CT) in 40 SD patients and 40 controls using voxel-based morphometry and cortical distance estimates. These measures were examined for relationships with blood oxygen level–dependent signal change during symptomatic syllable production in 15 of the same patients. SD patients had increased GMV, CT, and brain activation in key structures of the speech control system, including the laryngeal sensorimotor cortex, inferior frontal gyrus (IFG), superior/middle temporal and supramarginal gyri, and in a structure commonly abnormal in other primary dystonias, the cerebellum. Among these regions, GMV, CT and activation of the IFG and cerebellum showed positive relationships with SD severity, while CT of the IFG correlated with SD duration. The left anterior insula was the only region with decreased CT, which also correlated with SD symptom severity. These findings provide evidence for coupling between structural and functional abnormalities at different levels within the speech production system in SD. PMID:21666131

  17. Muscularity as a function of species, sex and age in small mammals

    NASA Technical Reports Server (NTRS)

    Pace, N.; Rahlmann, D. F.; Smith, A. H.

    1984-01-01

    Changes in the body skeletal muscle mass SMM (measured as a function of the ratio between the body creatine mass and the fat-free muscle creatine), and in muscularity (expressed as the ratio of SMM to fat-free body mass) were studied as functions of age, sex, and species in mouse, rat, hamster, guinea pig, and rabbit. Six animals of each sex were examined in eight age cohorts ranging from 1 to 24 months. Both species and age factors affect SMM. Strong sexual dimorphism in the SMM changes with age was displayed by mouse, rat, and guinea pig, whereas the hamster and rabbit were statistically monomorphic. The mouse, rat, and hamster attain a maximal SMM at about 1 year of age, whereas in the guinea pig and rabbit the decrease in SMM starts after 2 years. The value of muscularity reached a peak at age of 2-3 months in all animals of both sexes, with a pronounced difference among the species. The mouse emerged as the most muscular, while the guinea pig the least muscular, of all species.

  18. Cognitive and Neurobehavioral Profile in Boys With Duchenne Muscular Dystrophy.

    PubMed

    Banihani, Rudaina; Smile, Sharon; Yoon, Grace; Dupuis, Annie; Mosleh, Maureen; Snider, Andrea; McAdam, Laura

    2015-10-01

    Duchenne muscular dystrophy is a progressive neuromuscular condition that has a high rate of cognitive and learning disabilities as well as neurobehavioral disorders, some of which have been associated with disruption of dystrophin isoforms. Retrospective cohort of 59 boys investigated the cognitive and neurobehavioral profile of boys with Duchenne muscular dystrophy. Full-scale IQ of < 70 was seen in 27%; learning disability in 44%, intellectual disability in 19%; attention-deficit/hyperactivity disorder in 32%; autism spectrum disorders in 15%; and anxiety in 27%. Mutations affecting Dp260 isoform and 5'untranslated region of Dp140 were observed in 60% with learning disability, 50% intellectual disability, 77% with autism spectrum disorders, and 94% with anxiety. No statistically significant correlation was noted between comorbidities and dystrophin isoforms; however, there is a trend of cumulative loss of dystrophin isoforms with declining full-scale IQ. Enhanced psychology testing to include both cognitive and neurobehavioral disorders is recommended for all individuals with Duchenne muscular dystrophy. © The Author(s) 2015.

  19. Secondary Conditions Among Males With Duchenne or Becker Muscular Dystrophy.

    PubMed

    Latimer, Rebecca; Street, Natalie; Conway, Kristin Caspers; James, Kathy; Cunniff, Christopher; Oleszek, Joyce; Fox, Deborah; Ciafaloni, Emma; Westfield, Christina; Paramsothy, Pangaja

    2017-06-01

    Duchenne and Becker muscular dystrophy are X-linked neuromuscular disorders characterized by progressive muscle degeneration. Despite the involvement of multiple systems, secondary conditions among affected males have not been comprehensively described. Two hundred nine caregivers of affected males (aged 3-31 years) identified by the Muscular Dystrophy Surveillance, Tracking, and Research Network completed a mailed survey that included questions about secondary conditions impacting multiple body functions. The 5 most commonly reported conditions in males with Duchenne were cognitive deficits (38.4%), constipation (31.7%), anxiety (29.3%), depression (27.4%), and obesity (19.5%). Higher frequencies of anxiety, depression, and kidney stones were found among nonambulatory males compared to ambulatory males. Attention-deficit hyperactivity disorder (ADHD) was more common in ambulatory than nonambulatory males. These data support clinical care recommendations for monitoring of patients with Duchenne or Becker muscular dystrophy by a multidisciplinary team to prevent and treat conditions that may be secondary to the diagnosis.

  20. Secondary conditions among males with Duchenne or Becker muscular dystrophy

    PubMed Central

    Latimer, Rebecca; Street, Natalie; Conway, Kristin Caspers; James, Kathy; Cunniff, Christopher; Oleszek, Joyce; Fox, Deborah; Ciafaloni, Emma; Westfield, Christina; Paramsothy, Pangaja

    2017-01-01

    Duchenne and Becker muscular dystrophy are X-linked neuromuscular disorders characterized by progressive muscle degeneration. Despite the involvement of multiple systems, secondary conditions among affected males have not been comprehensively described. Two hundred and nine caregivers of affected males (aged 3–31 years) identified by the Muscular Dystrophy Surveillance, Tracking, and Research Network completed a mailed survey that included questions about secondary conditions impacting multiple body functions. The five most commonly reported conditions in males with Duchenne were cognitive deficits (38.4%), constipation (31.7%), anxiety (29.3%), depression (27.4%), and obesity (19.5%). Higher frequencies of anxiety, depression, and kidney stones, were found among non-ambulatory males compared to ambulatory males. Attention deficit hyperactivity disorder was more common in ambulatory than non-ambulatory males. These data support clinical care recommendations for monitoring of patients with Duchenne or Becker muscular dystrophy by a multidisciplinary team to prevent and treat conditions that may be secondary to the diagnosis. PMID:28393671

  1. Drive for muscularity and social physique anxiety mediate the perceived ideal physique muscle dysmorphia relationship.

    PubMed

    Thomas, Adam; Tod, David A; Edwards, Christian J; McGuigan, Michael R

    2014-12-01

    This study examined the mediating role of drive for muscularity and social physique anxiety (SPA) in the perceived muscular male ideal physique and muscle dysmorphia relationship in weight training men. Men (N = 146, mean ± SD; age, 22.8 ± 5.0 years; weight, 82.0 ± 11.1 kg; height, 1.80 ± 0.07 m; body mass index, 25.1 ± 3.0) who participated in weight training completed validated questionnaires measuring drive for muscularity, SPA, perceived muscular male ideal physique, global muscle dysmorphia, and several characteristics of muscle dysmorphia (exercise dependence, diet manipulation, concerns about size/symmetry, physique protection behavior, and supplementation). Perceived ideal physique was an independent predictor of muscle dysmorphia measures except physique protection (coefficients = 0.113-0.149, p ≤ 0.05). Perceived ideal physique also predicted muscle dysmorphia characteristics (except physique protection and diet) through the indirect drive for muscularity pathway (coefficients = 0.055-0.116, p ≤ 0.05). Perceived ideal physique also predicted size/symmetry concerns and physique protection through the indirect drive for muscularity and SPA pathway (coefficients = 0.080-0.025, p ≤ 0.05). These results extend current research by providing insights into the way correlates of muscle dysmorphia interact to predict the condition. The results also highlight signs (e.g., anxiety about muscularity) that strength and conditioning coaches can use to identify at-risk people who may benefit from being referred for psychological assistance.

  2. Decreased Insulin Receptors but Normal Glucose Metabolism in Duchenne Muscular Dystrophy

    NASA Astrophysics Data System (ADS)

    de Pirro, Roberto; Lauro, Renato; Testa, Ivano; Ferretti, Ginofabrizio; de Martinis, Carlo; Dellantonio, Renzo

    1982-04-01

    Compared to matched controls, 17 patients with Duchenne muscular dystrophy showed decreased insulin binding to monocytes due to decreased receptor concentration. These patients showed no signs of altered glucose metabolism and retrospective analysis of the clinical records of a further 56 such patients revealed no modification in carbohydrate metabolism. These data suggest that reduced insulin receptor number does not produce overt modifications of glucose metabolism in Duchenne muscular dystrophy.

  3. Nanolipodendrosome-loaded glatiramer acetate and myogenic differentiation 1 as augmentation therapeutic strategy approaches in muscular dystrophy

    PubMed Central

    Afzal, Ehsan; Zakeri, Saba; Keyhanvar, Peyman; Bagheri, Meisam; Mahjoubi, Parvin; Asadian, Mahtab; Omoomi, Nogol; Dehqanian, Mohammad; Ghalandarlaki, Negar; Darvishmohammadi, Tahmineh; Farjadian, Fatemeh; Golvajoee, Mohammad Sadegh; Afzal, Shadi; Ghaffari, Maryam; Cohan, Reza Ahangari; Gravand, Amin; Ardestani, Mehdi Shafiee

    2013-01-01

    Backgrond Muscular dystrophies consist of a number of juvenile and adult forms of complex disorders which generally cause weakness or efficiency defects affecting skeletal muscles or, in some kinds, other types of tissues in all parts of the body are vastly affected. In previous studies, it was observed that along with muscular dystrophy, immune inflammation was caused by inflammatory cells invasion – like T lymphocyte markers (CD8+/CD4+). Inflammatory processes play a major part in muscular fibrosis in muscular dystrophy patients. Additionally, a significant decrease in amounts of two myogenic recovery factors (myogenic differentation 1 [MyoD] and myogenin) in animal models was observed. The drug glatiramer acetate causes anti-inflammatory cytokines to increase and T helper (Th) cells to induce, in an as yet unknown mechanism. MyoD recovery activity in muscular cells justifies using it alongside this drug. Methods In this study, a nanolipodendrosome carrier as a drug delivery system was designed. The purpose of the system was to maximize the delivery and efficiency of the two drug factors, MyoD and myogenin, and introduce them as novel therapeutic agents in muscular dystrophy phenotypic mice. The generation of new muscular cells was analyzed in SW1 mice. Then, immune system changes and probable side effects after injecting the nanodrug formulations were investigated. Results The loaded lipodendrimer nanocarrier with the candidate drug, in comparison with the nandrolone control drug, caused a significant increase in muscular mass, a reduction in CD4+/CD8+ inflammation markers, and no significant toxicity was observed. The results support the hypothesis that the nanolipodendrimer containing the two candidate drugs will probably be an efficient means to ameliorate muscular degeneration, and warrants further investigation. PMID:23966782

  4. Abnormality of G-protein-coupled receptor kinases at prodromal and early stages of Alzheimer's disease: an association with early beta-amyloid accumulation.

    PubMed

    Suo, Zhiming; Wu, Min; Citron, Bruce A; Wong, Gwendolyn T; Festoff, Barry W

    2004-03-31

    Overwhelming evidence indicates that the effects of beta-amyloid (Abeta) are dose dependent both in vitro and in vivo, which implies that Abeta is not directly detrimental to brain cells until it reaches a threshold concentration. In an effort to understand early Alzheimer's disease (AD) pathogenesis, this study focused on the effects of subthreshold soluble Abeta and the underlying molecular mechanisms in murine microglial cells and an AD transgenic mouse model. We found that there were two phases of dose-dependent Abeta effects on microglial cells: at the threshold of 5 microm and above, Abeta directly induced tumor necrosis factor-alpha (TNF-alpha) release, and at subthreshold doses, Abeta indirectly potentiated TNF-alpha release induced by certain G-protein-coupled receptor (GPCR) activators. Mechanistic studies revealed that subthreshold Abeta pretreatment in vitro reduced membrane GPCR kinase-2/5 (GRK2/5), which led to retarded GPCR desensitization, prolonged GPCR signaling, and cellular hyperactivity to GPCR agonists. Temporal analysis in an early-onset AD transgenic model, CRND8 mice, revealed that the membrane (functional) GRK2/5 in brain cortices were significantly reduced. More importantly, such a GRK abnormality took place before cognitive decline and changed in a manner corresponding with the mild to moderate soluble Abeta accumulation in these transgenic mice. Together, this study not only discovered a novel link between subthreshold Abeta and GRK dysfunction, it also demonstrated that the GRK abnormality in vivo occurs at prodromal and early stages of AD.

  5. Venous pump of the calf: a study of venous and muscular pressures.

    PubMed

    Alimi, Y S; Barthelemy, P; Juhan, C

    1994-11-01

    Little data are available concerning the relation between the muscular pumping mechanism and the variation of superficial and deep venous pressure during normal action of the calf pump; therefore we undertook this study to determine the pressure values in three compartments of the calf and in the deep and the superficial venous system and to establish correlation between muscular and venous pressure. Nine healthy young women with a mean age of 23 years (range 19 to 28 years) were examined. In the same calf, a muscular catheter was placed in the deep posterior compartment (DPC), in the superficial posterior compartment (SPC), and in the anterior tibial compartment (ATC), and a vascular catheter was placed in the popliteal vein and in the greater saphenous vein (GSV). The five lines of pressure were simultaneously recorded in the following situations: at rest, during Valsalva maneuver, foot flexion, and foot extension. The situation was studied with the patient in the following positions: decubitus, sitting, standing, and squatting. A final continuous recording was carried out after the patient had been walking for 5 minutes. Mean values with standard errors of muscular and venous pressure were established in each situation. At rest and during Valsalva maneuver, the muscular pressures did not vary, whereas venous pressures increased significantly when the patient was sitting and standing. On the other hand, squatting was associated with a rise in the muscular and vein pressures. Foot flexion entailed a significant increase in the ATC pressure and a rise in the GSV pressure, whereas foot extension caused the DPC pressure to rise without venous pressure modifications. Walking was associated with an alternating increase in the DPC, SPC, GSV and popliteal vein pressures when the foot was compressed to floor followed by a significant decrease when the foot pressure was released. The variations in the deep and superficial venous pressures when the patient is sitting and

  6. Cardiomyopathy in becker muscular dystrophy: Overview.

    PubMed

    Ho, Rady; Nguyen, My-Le; Mather, Paul

    2016-06-26

    Becker muscular dystrophy (BMD) is an X-linked recessive disorder involving mutations of the dystrophin gene. Cardiac involvement in BMD has been described and cardiomyopathy represents the number one cause of death in these patients. In this paper, the pathophysiology, clinical evaluations and management of cardiomyopathy in patients with BMD will be discussed.

  7. Complementary and alternative medicine for Duchenne and Becker muscular dystrophies: characteristics of users and caregivers.

    PubMed

    Zhu, Yong; Romitti, Paul A; Conway, Kristin M; Andrews, Jennifer; Liu, Ke; Meaney, F John; Street, Natalie; Puzhankara, Soman; Druschel, Charlotte M; Matthews, Dennis J

    2014-07-01

    Complementary and alternative medicine is frequently used in the management of chronic pediatric diseases, but little is known about its use by those with Duchenne or Becker muscular dystrophy. Complementary and alternative medicine use by male patients with Duchenne or Becker muscular dystrophy and associations with characteristics of male patients and their caregivers were examined through interviews with 362 primary caregivers identified from the Muscular Dystrophy Surveillance, Tracking, and Research Network. Overall, 272 of the 362 (75.1%) primary caregivers reported that they had used any complementary and alternative medicine for the oldest Muscular Dystrophy Surveillance, Tracking, and Research Network male in their family. The most commonly reported therapies were from the mind-body medicine domain (61.0%) followed by those from the biologically based practice (39.2%), manipulative and body-based practice (29.3%), and whole medical system (6.9%) domains. Aquatherapy, prayer and/or blessing, special diet, and massage were the most frequently used therapies. Compared with nonusers, male patients who used any therapy were more likely to have an early onset of symptoms and use a wheel chair; their caregivers were more likely to be non-Hispanic white. Among domains, associations were observed with caregiver education and family income (mind-body medicines [excluding prayer and/or blessing only] and whole medical systems) and Muscular Dystrophy Surveillance, Tracking, and Research Network site (biologically based practices and mind-body medicines [excluding prayer and/or blessing only]). Complementary and alternative medicine use was common in the management of Duchenne and Becker muscular dystrophies among Muscular Dystrophy Surveillance, Tracking, and Research Network males. This widespread use suggests further study to evaluate the efficacy of integrating complementary and alternative medicine into treatment regimens for Duchenne and Becker muscular

  8. Genetics Home Reference: limb-girdle muscular dystrophy

    MedlinePlus

    ... age of onset, and features of limb-girdle muscle dystrophy vary among the many subtypes of this condition ... occurs in some people with limb-girdle muscular dystrophy . Weakening of the heart muscle (cardiomyopathy) occurs in some forms of limb-girdle ...

  9. GPR56-Related Polymicrogyria: Clinicoradiologic Profile of 4 Patients.

    PubMed

    Desai, Neelu A; Udani, Vrajesh

    2015-11-01

    Bilateral frontoparietal polymicrogyria is an autosomal recessive cortical malformation associated with abnormalities of neuronal migration, white matter changes, and mild brainstem and cerebellar abnormalities. Affected patients present with delayed milestones, intellectual disability, epilepsy, ataxia, and eye movement abnormalities. The clinicoradiologic profile resembles congenital muscular dystrophy. However, no muscle disease or characteristic eye abnormalities of congenial muscular dystrophy are detected in these children. GPR56 is the only confirmed gene associated with bilateral frontoparietal polymicrogyria. Antenatal diagnosis is possible if the index case is genetically confirmed. Four patients from different Indian families with a distinct clinicoradiologic profile resembling congenital muscular dystrophy with mutations in the GPR56 gene are described. © The Author(s) 2015.

  10. Development of a Force Measurement Device for Lower-Body Muscular Strength Measuring of Skaters

    NASA Astrophysics Data System (ADS)

    Kim, Dong Ki; Lee, Jeong Tae

    This paper presents a force measurement system that can measure a lower-body muscular strength of skaters. The precise measurement and analysis of the left and right lower-body strength of skaters is necessary, because a left/right lower-body strength balance is helpful to improve the athletes' performance and to protect them from injury. The system is constructed with a skate sliding board, a couple of sensor-units with load cell, indicator and control box, guard, force pad, and support bracket. The developed force measurement system is calibrated by the calibration setup, and the uncertainty of the force sensing unit on the left is within 0.087% and the uncertainty of the force sensing unit on the right is within 0.109%. In order to check the feasibility of the developed measurement device, a kinematic analysis is conducted with skater. As a result, the subject shows the deviation of left and right of 12.1 N with respect to average strength and 39.1 N with respect to the maximum strength. This evaluation results are reliable enough to make it possible to measure a lower-body muscular strength of skaters. The use of this measurement system will be expected to correct the posture of skaters and record the sports dynamics data for each athlete. It is believed that through the development of this equipment, skaters in elementary, middle, high schools, colleges, and the professional level have the systematic training to compete with world-class skaters.

  11. Zidovudine ameliorates pathology in the mouse model of Duchenne muscular dystrophy via P2RX7 purinoceptor antagonism.

    PubMed

    Al-Khalidi, Rasha; Panicucci, Chiara; Cox, Paul; Chira, Natalia; Róg, Justyna; Young, Christopher N J; McGeehan, Rhiannon E; Ambati, Kameshwari; Ambati, Jayakrishna; Zabłocki, Krzysztof; Gazzerro, Elisabetta; Arkle, Stephen; Bruno, Claudio; Górecki, Dariusz C

    2018-04-11

    Duchenne muscular dystrophy (DMD) is the most common inherited muscle disorder that causes severe disability and death of young men. This disease is characterized by progressive muscle degeneration aggravated by sterile inflammation and is also associated with cognitive impairment and low bone density. Given that no current treatment can improve the long-term outcome, approaches with a strong translational potential are urgently needed. Duchenne muscular dystrophy (DMD) alters P2RX7 signaling in both muscle and inflammatory cells and inhibition of this receptor resulted in a significant attenuation of muscle and non-muscle symptoms in DMD mdx mouse model. As P2RX7 is an attractive target in a range of human diseases, specific antagonists have been developed. Yet, these will require lengthy safety testing in the pediatric population of Duchenne muscular dystrophy (DMD) patients. In contrast, Nucleoside Reverse Transcriptase Inhibitors (NRTIs) can act as P2RX7 antagonists and are drugs with an established safety record, including in children. We demonstrate here that AZT (Zidovudine) inhibits P2RX7 functions acting via the same allosteric site as other antagonists. Moreover, short-term AZT treatment at the peak of disease in DMD mdx mice attenuated the phenotype without any detectable side effects. Recovery was evident in the key parameters such as reduced sarcolemma permeability confirmed by lower serum creatine kinase levels and IgG influx into myofibres, decreased inflammatory cell numbers and inflammation markers in leg and heart muscles of treated mice. Moreover, this short-term therapy had some positive impact on muscle strength in vivo and no detrimental effect on mitochondria, which is the main side-effect of Nucleoside Reverse Transcriptase Inhibitors (NRTIs). Given these results, we postulate that AZT could be quickly re-purposed for the treatment of this highly debilitating and lethal disease. This approach is not constrained by causative DMD mutations and

  12. Drive for muscularity and drive for thinness: the impact of pro-anorexia websites.

    PubMed

    Juarez, Lilia; Soto, Ernesto; Pritchard, Mary E

    2012-01-01

    In recent years, websites that stress the message of thinness as the ideal and only choice have surfaced on the internet. The possibility that pro-anorexia websites may reinforce restrictive eating and exercise behaviors is an area of concern. In addition, friends may be influencing one another to view these websites, further contributing to drive for thinness in women and drive for muscularity in men. Three hundred male and female undergraduate psychology students responded to questionnaires assessing: internalization of pro-anorexia website content, internalization of general media content, influence of friends to view pro-anorexia websites, peer influence, drive for muscularity, and drive for thinness. Results showed internalization of pro-anorexia website content was positively correlated with drive for thinness in women, and negatively correlated with drive for muscularity in men. Internalization of pro-anorexia website content was found to be related to both drive for thinness in women and drive for muscularity in men.

  13. The effects of exposure to slender and muscular images on male body dissatisfaction.

    PubMed

    Galioto, Rachel; Crowther, Janis H

    2013-09-01

    This research examined the effects of appearance-based comparisons to muscular and slender idealized male bodies and the contribution of internalization and social comparison to change in body dissatisfaction. Participants were 111 male undergraduates who completed measures of body dissatisfaction, internalization, and social comparison and viewed images of either muscular or slender men in advertisements or product-only advertisements. Results indicated that exposure to both muscular and slender images was associated with an increase in body dissatisfaction, with no significant differences in the change in body dissatisfaction between the two image conditions. Internalization and trait social comparison were each associated with an increase in body dissatisfaction; however, upward social comparison was only a significant predictor of a change in body dissatisfaction for the males who viewed muscular images. These results highlight the impact of slender models on young men's body dissatisfaction and support the examination of media literacy interventions with this population. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Sparks, signals and shock absorbers: how dystrophin loss causes muscular dystrophy.

    PubMed

    Batchelor, Clare L; Winder, Steve J

    2006-04-01

    The dystrophin-glycoprotein complex (DGC) can be considered as a specialized adhesion complex, linking the extracellular matrix to the actin cytoskeleton, primarily in muscle cells. Mutations in several components of the DGC lead to its partial or total loss, resulting in various forms of muscular dystrophy. These typically manifest as progressive wasting diseases with loss of muscle integrity. Debate is ongoing about the precise function of the DGC: initially a strictly mechanical role was proposed but it has been suggested that there is aberrant calcium handling in muscular dystrophy and, more recently, changes in MAP kinase and GTPase signalling have been implicated in the aetiology of the disease. Here, we discuss new and interesting developments in these aspects of DGC function and attempt to rationalize the mechanical, calcium and signalling hypotheses to provide a unifying hypothesis of the underlying process of muscular dystrophy.

  15. Late-onset Becker-type muscular dystrophy in a Border terrier dog.

    PubMed

    Jeandel, A; Garosi, L S; Davies, L; Guo, L T; Salgüero, R; Shelton, G D

    2018-01-29

    A 9-year-old Border terrier was presented to a referral hospital after a 1-year history of progressive stiffness and exercise intolerance. Neurological examination was consistent with a neuromuscular disorder. Serum creatine kinase activity was mildly elevated. A myopathy was suspected based on MRI findings and electrophysiological examination. Muscle histopathology was consistent with a severe non-inflammatory myopathy of a dystrophic type. Immunofluorescence and western blotting confirmed a dystrophinopathy with an 80-kDa truncated dystrophin fragment similar to Becker muscular dystrophy in people. To our knowledge, this is the first description of a late-onset Becker-type muscular dystrophy in a dog, and the first description of a dystrophinopathy in a Border terrier. Muscular dystrophy in dogs should not be ruled out based on late onset clinical signs and only mildly elevated creatine kinase. © 2018 British Small Animal Veterinary Association.

  16. Effects of the Abnormal Acceleratory Environment of Flight

    DTIC Science & Technology

    1974-12-01

    vision Return of arteriolar pulsa- tion and temporary venous distension Visual failure is a continuum from loss of peripheral vision (grey- out) to...distance); intrathoracic pressure is increased by strong muscular expiratorv efforts against a partially closed glottis; and the contraction of...vigorous skeletal muscular tensing (Valsalva maneuver) can reduce +GZ tolerance and lead to an episode of unconsciousness at extremely low G levels

  17. Nose muscular dynamics: the tip trigonum.

    PubMed

    Figallo, E E; Acosta, J A

    2001-10-01

    In 1995, the senior author (E.E.F.) published an article in which he described the musculus digastricus septi nasi labialis. In the article presented here, work carried out by anatomists and other researchers who, over the last two centuries, studied nose muscular dynamics is described. The present study is based on Gray's Anatomy, which, in 1858, first described the nasal tip muscles, along with the other nasal muscles. Later works not only used different terminology for these muscles but also ignored some, creating tremendous confusion. The study presented here provides an update of the exact terms, location, insertions, and muscle functions of the muscles of the nose. Each nose muscle is described with regard to the two portions able to produce separate contractions. In this study, the term "dual function" is used and characterizes the nasal mimetic muscles that do not have well-defined fascia. Therefore, there is doubt about the existence of a real nasal superficial muscle aponeurotic system. The musculus myrtiformis seems to have a dual function, inserting in the canine fosse and in the periosteum of the central incisors, forming two portions-one to the septum and the other to the nostril-each of which has specific functions. This study has been based on research in physiognomy, the science of expression. With regard to the basis for nose expressions, common anatomical research is excluded because it provides a different view of the dynamics studied to date. The term trigonum musculare apicis nasi defines the interaction of the musculi compressor narium minor and dilator naris anterior, connecting with the columellar bundle of the musculus digastricus and levering the nasal spine. This muscular trigone creates circular concentric and eccentric movements of the nasal tip.

  18. Physical Activity in Boys With Duchenne Muscular Dystrophy Is Lower and Less Demanding Compared to Healthy Boys.

    PubMed

    Heutinck, Lotte; Kampen, Nadine van; Jansen, Merel; Groot, Imelda J M de

    2017-04-01

    This study describes the amount of physical activity and perception of physical activity in boys with Duchenne muscular dystrophy (DMD) compared to healthy boys. A questionnaire described 6 domains of physical activity. Four Duchenne muscular dystrophy subgroups were made: early and late ambulatory, nonambulatory with relative good, or limited arm function. Eighty-four boys with Duchenne muscular dystrophy (15.0 ± 6.4 years) and 198 healthy boys (14.0 ± 4.3 years) participated. Daily activities were more passive for boys with Duchenne muscular dystrophy. Physical activity was less and low demanding compared to healthy boys. It decreased with disease severity ( P < .05), whereas screen time increased ( P < .05). Benefits of physical activity in boys with Duchenne muscular dystrophy were having fun and making friends. Barriers were lack of sport facilities and insufficient health. This study helps to quantify poor engagement in physical activity by boys with Duchenne muscular dystrophy, and demonstrates factors that contribute to it. Suggestions to stimulate physical activity are made.

  19. Muscular pattern in three species of Macrostomum (platyhelminthes, macrostomorpha).

    PubMed

    Adami, Mariana L; Brusa, Francisco; Ronderos, Jorge R; Damborenea, Cristina

    2017-02-01

    Previous studies demonstrated complex architecture of the muscular system of Macrostomum species, especially in the rostrum area and the pharynx. However, little is known about the differences in muscular pattern between species of the genus. This study examines and compares the muscular systems of specimens belonging to three freshwater Macrostomum species (M. quiritium, M. tuba and M. velastylum), labeled with phalloidin-rhodamine and studied by confocal microscopy. Our results agree with the previous descriptions, confirming that the muscular patterns for the body wall, rostrum area, pharynx and caudal region differ among species. The muscles of the body wall follow the typical architecture, but the number of fibers in the species analyzed varies between dorsal and ventral surfaces, ranging from 80 to 100 fibers, this record being higher than previous observations. The arrangement of the fibers in the rostrum is complex, especially in the brain area. Macrostomum tuba and M. quiritium have a set of two muscles crossing at brain level and forming an "X," which is not evident in M. velastylum. We identified five different sets of fibers associated to the pharynx and mouth at ventral, medium and deep levels. These different sets are present in all three species studied. The caudal plate in M. tuba has an additional layer of diagonal fibers in the body wall, which is not evident in the other two species. The muscles of the reproductive system are independent of the body wall musculature in the species analyzed, but connected to the intestinal wall by specific fibers that may serve as an anchor. J. Morphol. 278:264-282, 2017. © 2016 Wiley Periodicals,Inc. © 2016 Wiley Periodicals, Inc.

  20. Cardiomyopathy in becker muscular dystrophy: Overview

    PubMed Central

    Ho, Rady; Nguyen, My-Le; Mather, Paul

    2016-01-01

    Becker muscular dystrophy (BMD) is an X-linked recessive disorder involving mutations of the dystrophin gene. Cardiac involvement in BMD has been described and cardiomyopathy represents the number one cause of death in these patients. In this paper, the pathophysiology, clinical evaluations and management of cardiomyopathy in patients with BMD will be discussed. PMID:27354892

  1. Translational Studies of GALGT2 Gene Therapy for Duchenne Muscular Dystrophy

    DTIC Science & Technology

    2013-10-01

    muscles once the experimental problems related to expression are solved. Figure 2. Percentage change in specific force after GALGT2 treatment of wild...cytotoxic T cell GalNAc transferase in skeletal muscle inhibits muscular dystrophy in mdx mice. Proc Natl Acad Sci U S A 99, 5616-5621 (2002). 3. Xu, R...Camboni, M. & Martin, P.T. Postnatal overexpression of the CT GalNAc transferase inhibits muscular dystrophy in mdx mice without altering muscle growth

  2. COUP-TFII regulates satellite cell function and muscular dystrophy.

    PubMed

    Xie, Xin; Tsai, Sophia Y; Tsai, Ming-Jer

    2016-10-03

    Duchenne muscular dystrophy (DMD) is a severe and progressive muscle-wasting disease caused by mutations in the dystrophin gene. Although dystrophin deficiency in myofiber triggers the disease's pathological changes, the degree of satellite cell (SC) dysfunction defines disease progression. Here, we have identified chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) hyperactivity as a contributing factor underlying muscular dystrophy in a dystrophin-deficient murine model of DMD. Ectopic expression of COUP-TFII in murine SCs led to Duchenne-like dystrophy in the muscles of control animals and exacerbated degenerative myopathies in dystrophin-deficient mice. COUP-TFII-overexpressing mice exhibited regenerative failure that was attributed to deficient SC proliferation and myoblast fusion. Mechanistically, we determined that COUP-TFII coordinated a regenerative program through combined regulation of multiple promyogenic factors. Furthermore, inhibition of COUP-TFII preserved SC function and counteracted the muscle weakness associated with Duchenne-like dystrophy in the murine model, suggesting that targeting COUP-TFII is a potential treatment for DMD. Together, our findings reveal a regulatory role of COUP-TFII in the development of muscular dystrophy and open up a potential therapeutic opportunity for managing disease progression in patients with DMD.

  3. Association of physical activity with muscular strength and fat-free mass in adolescents: the HELENA study.

    PubMed

    Moliner-Urdiales, Diego; Ortega, Francisco B; Vicente-Rodriguez, Germán; Rey-Lopez, Juan P; Gracia-Marco, Luis; Widhalm, Kurt; Sjöström, Michael; Moreno, Luis A; Castillo, Manuel J; Ruiz, Jonatan R

    2010-08-01

    The objective of this study is to analyse the association of objectively assessed physical activity (PA) with muscular strength and fat-free mass in adolescents, and to determine whether meeting the current PA recommendations is associated with higher levels of muscular strength and fat-free mass. The present cross-sectional study comprised 363 Spanish adolescents (180 females) aged 12.5-17.5 years. PA was assessed by accelerometry and expressed as average PA (counts/min), and min/day of inactive, light, moderate, vigorous and moderate to vigorous PA (MVPA). MVPA was dichotomized into < 60 min/day and > or = 60. Upper body muscular strength was measured with the handgrip strength test, and lower body muscular strength was measured with the standing broad jump, squat jump, counter movement jump and Abalakov tests. Fat-free mass was measured by DXA. We observed positive associations between vigorous PA and all the lower body muscular strength tests except for the counter movement jump in males. PA was not associated with fat-free mass in both males and females. Male adolescents engaged in at least 60 min/day MVPA performed better in the standing broad jump test. In conclusion, the findings of the present study suggest that only vigorous PA is associated with muscular strength, particularly lower-body muscular strength in male adolescents.

  4. Oxidative stress and pathology in muscular dystrophies: focus on protein thiol oxidation and dysferlinopathies.

    PubMed

    Terrill, Jessica R; Radley-Crabb, Hannah G; Iwasaki, Tomohito; Lemckert, Frances A; Arthur, Peter G; Grounds, Miranda D

    2013-09-01

    The muscular dystrophies comprise more than 30 clinical disorders that are characterized by progressive skeletal muscle wasting and degeneration. Although the genetic basis for many of these disorders has been identified, the exact mechanism for pathogenesis generally remains unknown. It is considered that disturbed levels of reactive oxygen species (ROS) contribute to the pathology of many muscular dystrophies. Reactive oxygen species and oxidative stress may cause cellular damage by directly and irreversibly damaging macromolecules such as proteins, membrane lipids and DNA; another major cellular consequence of reactive oxygen species is the reversible modification of protein thiol side chains that may affect many aspects of molecular function. Irreversible oxidative damage of protein and lipids has been widely studied in Duchenne muscular dystrophy, and we have recently identified increased protein thiol oxidation in dystrophic muscles of the mdx mouse model for Duchenne muscular dystrophy. This review evaluates the role of elevated oxidative stress in Duchenne muscular dystrophy and other forms of muscular dystrophies, and presents new data that show significantly increased protein thiol oxidation and high levels of lipofuscin (a measure of cumulative oxidative damage) in dysferlin-deficient muscles of A/J mice at various ages. The significance of this elevated oxidative stress and high levels of reversible thiol oxidation, but minimal myofibre necrosis, is discussed in the context of the disease mechanism for dysferlinopathies, and compared with the situation for dystrophin-deficient mdx mice. © 2013 The Authors Journal compilation © 2013 FEBS.

  5. Living with illness and self-transcendence: the lived experience of patients with spinal muscular atrophy.

    PubMed

    Ho, Hsin-Mei; Tseng, Ying-Hua; Hsin, Yu-Mei; Chou, Fan-Hao; Lin, Wei-Ting

    2016-11-01

    The aim of this study was to explore the lived experiences of patients afflicted with spinal muscular atrophy. Existing research studies on spinal muscular atrophy address the physical and psychological effects and complications of the disease; they also provide suggestions for how to improve the current management of this disease. However, information is limited on the disease process and the lived experience of spinal muscular atrophy patients. A phenomenological approach was conducted. Through 18 in-depth interviews recorded by a pen voice recorder, this study collected data obtained from a purposive sample of nine patients from the, 'Taiwan spinal muscular atrophy Families,' between November 2010-August 2011. The audio recordings were transcribed verbatim and data were analysed using Colaizzi's steps. Four themes and eight subthemes were identified: a loss of control (loss of muscular strength and independence), breaking limitations (assistive device use and mobility design), transcending limitations (independence/autonomy and social development) and living with hope (cherishing life and self-control). The results showed that the lived experiences of the spinal muscular atrophy patients involved living with illness, transcending the self and pursuing the meaning of life. Facing a life-threatening illness, these patients made self-adjustments in their lifestyles and exerted themselves to positively cope with hardships and maintain dignity and self-control. These findings could serve as evidence-based practice resources for healthcare professionals in helping individuals and their family members gain an in-depth understanding of spinal muscular atrophy's progression and life course and assist individuals in improving self-integrity to with hope. © 2016 John Wiley & Sons Ltd.

  6. Congenital Bone Fractures in Spinal Muscular Atrophy: Functional Role for SMN Protein in Bone Remodeling

    PubMed Central

    Shanmugarajan, Srinivasan; Swoboda, Kathryn J.; Iannaccone, Susan T.; Ries, William L.; Maria, Bernard L.; Reddy, Sakamuri V.

    2009-01-01

    Spinal muscular atrophy is the second most common fatal childhood disorder. Core clinical features include muscle weakness caused by degenerating lower motor neurons and a high incidence of bone fractures and hypercalcemia. Fractures further compromise quality of life by progression of joint contractures or additional loss of motor function. Recent observations suggest that bone disease in spinal muscular atrophy may not be attributed entirely to lower motor neuron degeneration. The presence of the spinal muscular atrophy disease-determining survival motor neuron gene (SMN), SMN expression, and differential splicing in bone-resorbing osteoclasts was recently discovered. Its ubiquitous expression and the differential expression of splice variants suggest that SMN has specific roles in bone cell function. SMN protein also interacts with osteoclast stimulatory factor. Mouse models of human spinal muscular atrophy disease suggest a potential role of SMN protein in skeletal development. Dual energy x-ray absorptiometry analysis demonstrated a substantial decrease in total bone area and poorly developed caudal vertebra in the mouse model. These mice also had pelvic bone fractures. Studies delineating SMN signaling mechanisms and gene transcription in a cell-specific manner will provide important molecular insights into the pathogenesis of bone disease in children with spinal muscular atrophy. Moreover, understanding bone remodeling in spinal muscular atrophy may lead to novel therapeutic approaches to enhance skeletal health and quality of life. This article reviews the skeletal complications associated with spinal muscular atrophy and describes a functional role for SMN protein in osteoclast development and bone resorption activity. PMID:17761651

  7. Cardiac manifestations of congenital LMNA-related muscular dystrophy in children: three case reports and recommendations for care.

    PubMed

    Heller, Felice; Dabaj, Ivana; Mah, Jean K; Bergounioux, Jean; Essid, Aben; Bönnemann, Carsten G; Rutkowski, Anne; Bonne, Gisèle; Quijano-Roy, Susana; Wahbi, Karim

    2017-08-01

    Skeletal and cardiac muscle laminopathies, caused by mutations in the lamin A/C gene, have a clinical spectrum from congenital LMNA-related muscular dystrophy to later-onset Emery-Dreifuss muscular dystrophy, limb girdle muscular dystrophy, and dilated cardiomyopathy. Although cardiac involvement is observed at all ages, it has only been well described in adults. We present the evolution of cardiac disease in three children with congenital muscular dystrophy presentation of LMNA-related muscular dystrophy. In this series, atrial arrhythmia was the presenting cardiac finding in all three patients. Heart failure developed up to 5 years later. Symptoms of right heart failure, including diarrhoea and peripheral oedema, preceded a rapid decline in left ventricular ejection fraction. Recommendations for cardiac surveillance and management in these patients are made.

  8. Perceptions of health and attractiveness: the effects of body fat, muscularity, gender, and ethnicity.

    PubMed

    Yanover, Tovah; Thompson, J Kevin

    2010-10-01

    Three hundred and thirty-three participants rated the health and attractiveness of schematic figures varying in muscularity, adiposity, gender, and race. In general, overweight and underweight figures were rated as less healthy and attractive. However, overweight figures with high levels of muscularity were rated more highly on these dimensions than figures with less muscularity. Females assigned higher attractiveness ratings than males; African Americans provided higher ratings than Caucasians and Hispanics for female figures and lower ratings than Caucasian and Hispanic raters for male figures. Theoretical explanations and applied implications are offered.

  9. Masculinities and ethnicities: Ethnic differences in drive for muscularity in British men and the negotiation of masculinity hierarchies.

    PubMed

    Swami, Viren

    2016-08-01

    Although relatively little is known about ethnic differences in men's drive for muscularity, recent theoretical developments suggest that ethnic minority men may desire greater muscularity to contest their positions of relative subordinate masculinity. This study tested this hypothesis in a sample of 185 White, 180 Black British, and 182 South Asian British men. Participants completed self-report measures of drive for muscularity, need for power, adherence to traditional cultural values, and ethnic group affiliation. Taking into account between-group differences in body mass index, results indicated that White men had significantly lower drive for muscularity than Black and South Asian men, who were not significantly different from each other. In addition, greater need for power was significantly associated with higher drive for muscularity in ethnic minority, but not White, men. Greater adherence to traditional cultural values, but not ethnic group affiliation, was associated with lower drive for muscularity in all ethnic groups. These results suggest that ethnic minority men may desire greater muscularity as a means of negotiating masculinity and attendant ideals of appearance. © 2015 The British Psychological Society.

  10. Wnt signaling pathway improves central inhibitory synaptic transmission in a mouse model of Duchenne muscular dystrophy.

    PubMed

    Fuenzalida, Marco; Espinoza, Claudia; Pérez, Miguel Ángel; Tapia-Rojas, Cheril; Cuitino, Loreto; Brandan, Enrique; Inestrosa, Nibaldo C

    2016-02-01

    The dystrophin-associated glycoprotein complex (DGC) that connects the cytoskeleton, plasma membrane and the extracellular matrix has been related to the maintenance and stabilization of channels and synaptic receptors, which are both essential for synaptogenesis and synaptic transmission. The dystrophin-deficient (mdx) mouse model of Duchenne muscular dystrophy (DMD) exhibits a significant reduction in hippocampal GABA efficacy, which may underlie the altered synaptic function and abnormal hippocampal long-term plasticity exhibited by mdx mice. Emerging studies have implicated Wnt signaling in the modulation of synaptic efficacy, neuronal plasticity and cognitive function. We report here that the activation of the non-canonical Wnt-5a pathway and Andrographolide, improves hippocampal mdx GABAergic efficacy by increasing the number of inhibitory synapses and GABA(A) receptors or GABA release. These results indicate that Wnt signaling modulates GABA synaptic efficacy and could be a promising novel target for DMD cognitive therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Gait characterization in golden retriever muscular dystrophy dogs using linear discriminant analysis.

    PubMed

    Fraysse, Bodvaël; Barthélémy, Inès; Qannari, El Mostafa; Rouger, Karl; Thorin, Chantal; Blot, Stéphane; Le Guiner, Caroline; Chérel, Yan; Hogrel, Jean-Yves

    2017-04-12

    Accelerometric analysis of gait abnormalities in golden retriever muscular dystrophy (GRMD) dogs is of limited sensitivity, and produces highly complex data. The use of discriminant analysis may enable simpler and more sensitive evaluation of treatment benefits in this important preclinical model. Accelerometry was performed twice monthly between the ages of 2 and 12 months on 8 healthy and 20 GRMD dogs. Seven accelerometric parameters were analysed using linear discriminant analysis (LDA). Manipulation of the dependent and independent variables produced three distinct models. The ability of each model to detect gait alterations and their pattern change with age was tested using a leave-one-out cross-validation approach. Selecting genotype (healthy or GRMD) as the dependent variable resulted in a model (Model 1) allowing a good discrimination between the gait phenotype of GRMD and healthy dogs. However, this model was not sufficiently representative of the disease progression. In Model 2, age in months was added as a supplementary dependent variable (GRMD_2 to GRMD_12 and Healthy_2 to Healthy_9.5), resulting in a high overall misclassification rate (83.2%). To improve accuracy, a third model (Model 3) was created in which age was also included as an explanatory variable. This resulted in an overall misclassification rate lower than 12%. Model 3 was evaluated using blinded data pertaining to 81 healthy and GRMD dogs. In all but one case, the model correctly matched gait phenotype to the actual genotype. Finally, we used Model 3 to reanalyse data from a previous study regarding the effects of immunosuppressive treatments on muscular dystrophy in GRMD dogs. Our model identified significant effect of immunosuppressive treatments on gait quality, corroborating the original findings, with the added advantages of direct statistical analysis with greater sensitivity and more comprehensible data representation. Gait analysis using LDA allows for improved analysis of

  12. Weekly Time Course of Neuro-Muscular Adaptation to Intensive Strength Training.

    PubMed

    Brown, Niklas; Bubeck, Dieter; Haeufle, Daniel F B; Weickenmeier, Johannes; Kuhl, Ellen; Alt, Wilfried; Schmitt, Syn

    2017-01-01

    Detailed description of the time course of muscular adaptation is rarely found in literature. Thus, models of muscular adaptation are difficult to validate since no detailed data of adaptation are available. In this article, as an initial step toward a detailed description and analysis of muscular adaptation, we provide a case report of 8 weeks of intense strength training with two active, male participants. Muscular adaptations were analyzed on a morphological level with MRI scans of the right quadriceps muscle and the calculation of muscle volume, on a voluntary strength level by isometric voluntary contractions with doublet stimulation (interpolated twitch technique) and on a non-voluntary level by resting twitch torques. Further, training volume and isokinetic power were closely monitored during the training phase. Data were analyzed weekly for 1 week prior to training, pre-training, 8 weeks of training and 2 weeks of detraining (no strength training). Results show a very individual adaptation to the intense strength training protocol. While training volume and isokinetic power increased linearly during the training phase, resting twitch parameters decreased for both participants after the first week of training and stayed below baseline until de-training. Voluntary activation level showed an increase in the first 4 weeks of training, while maximum voluntary contraction showed only little increase compared to baseline. Muscle volume increased for both subjects. Especially training status seemed to influence the acute reaction to intense strength training. Fatigue had a major influence on performance and could only be overcome by one participant. The results give a first detailed insight into muscular adaptation to intense strength training on various levels, providing a basis of data for a validation of muscle fatigue and adaptation models.

  13. A method to accurately estimate the muscular torques of human wearing exoskeletons by torque sensors.

    PubMed

    Hwang, Beomsoo; Jeon, Doyoung

    2015-04-09

    In exoskeletal robots, the quantification of the user's muscular effort is important to recognize the user's motion intentions and evaluate motor abilities. In this paper, we attempt to estimate users' muscular efforts accurately using joint torque sensor which contains the measurements of dynamic effect of human body such as the inertial, Coriolis, and gravitational torques as well as torque by active muscular effort. It is important to extract the dynamic effects of the user's limb accurately from the measured torque. The user's limb dynamics are formulated and a convenient method of identifying user-specific parameters is suggested for estimating the user's muscular torque in robotic exoskeletons. Experiments were carried out on a wheelchair-integrated lower limb exoskeleton, EXOwheel, which was equipped with torque sensors in the hip and knee joints. The proposed methods were evaluated by 10 healthy participants during body weight-supported gait training. The experimental results show that the torque sensors are to estimate the muscular torque accurately in cases of relaxed and activated muscle conditions.

  14. A Method to Accurately Estimate the Muscular Torques of Human Wearing Exoskeletons by Torque Sensors

    PubMed Central

    Hwang, Beomsoo; Jeon, Doyoung

    2015-01-01

    In exoskeletal robots, the quantification of the user’s muscular effort is important to recognize the user’s motion intentions and evaluate motor abilities. In this paper, we attempt to estimate users’ muscular efforts accurately using joint torque sensor which contains the measurements of dynamic effect of human body such as the inertial, Coriolis, and gravitational torques as well as torque by active muscular effort. It is important to extract the dynamic effects of the user’s limb accurately from the measured torque. The user’s limb dynamics are formulated and a convenient method of identifying user-specific parameters is suggested for estimating the user’s muscular torque in robotic exoskeletons. Experiments were carried out on a wheelchair-integrated lower limb exoskeleton, EXOwheel, which was equipped with torque sensors in the hip and knee joints. The proposed methods were evaluated by 10 healthy participants during body weight-supported gait training. The experimental results show that the torque sensors are to estimate the muscular torque accurately in cases of relaxed and activated muscle conditions. PMID:25860074

  15. Skeletal Muscle Metabolism in Duchenne and Becker Muscular Dystrophy-Implications for Therapies.

    PubMed

    Heydemann, Ahlke

    2018-06-20

    The interactions between nutrition and metabolism and skeletal muscle have long been known. Muscle is the major metabolic organ—it consumes more calories than other organs—and therefore, there is a clear need to discuss these interactions and provide some direction for future research areas regarding muscle pathologies. In addition, new experiments and manuscripts continually reveal additional highly intricate, reciprocal interactions between metabolism and muscle. These reciprocal interactions include exercise, age, sex, diet, and pathologies including atrophy, hypoxia, obesity, diabetes, and muscle myopathies. Central to this review are the metabolic changes that occur in the skeletal muscle cells of muscular dystrophy patients and mouse models. Many of these metabolic changes are pathogenic (inappropriate body mass changes, mitochondrial dysfunction, reduced adenosine triphosphate (ATP) levels, and increased Ca 2+ ) and others are compensatory (increased phosphorylated AMP activated protein kinase (pAMPK), increased slow fiber numbers, and increased utrophin). Therefore, reversing or enhancing these changes with therapies will aid the patients. The multiple therapeutic targets to reverse or enhance the metabolic pathways will be discussed. Among the therapeutic targets are increasing pAMPK, utrophin, mitochondrial number and slow fiber characteristics, and inhibiting reactive oxygen species. Because new data reveals many additional intricate levels of interactions, new questions are rapidly arising. How does muscular dystrophy alter metabolism, and are the changes compensatory or pathogenic? How does metabolism affect muscular dystrophy? Of course, the most profound question is whether clinicians can therapeutically target nutrition and metabolism for muscular dystrophy patient benefit? Obtaining the answers to these questions will greatly aid patients with muscular dystrophy.

  16. Effects of systemic hypoxia on human muscular adaptations to resistance exercise training

    PubMed Central

    Kon, Michihiro; Ohiwa, Nao; Honda, Akiko; Matsubayashi, Takeo; Ikeda, Tatsuaki; Akimoto, Takayuki; Suzuki, Yasuhiro; Hirano, Yuichi; Russell, Aaron P.

    2014-01-01

    Abstract Hypoxia is an important modulator of endurance exercise‐induced oxidative adaptations in skeletal muscle. However, whether hypoxia affects resistance exercise‐induced muscle adaptations remains unknown. Here, we determined the effect of resistance exercise training under systemic hypoxia on muscular adaptations known to occur following both resistance and endurance exercise training, including muscle cross‐sectional area (CSA), one‐repetition maximum (1RM), muscular endurance, and makers of mitochondrial biogenesis and angiogenesis, such as peroxisome proliferator‐activated receptor‐γ coactivator‐1α (PGC‐1α), citrate synthase (CS) activity, nitric oxide synthase (NOS), vascular endothelial growth factor (VEGF), hypoxia‐inducible factor‐1 (HIF‐1), and capillary‐to‐fiber ratio. Sixteen healthy male subjects were randomly assigned to either a normoxic resistance training group (NRT, n =7) or a hypoxic (14.4% oxygen) resistance training group (HRT, n =9) and performed 8 weeks of resistance training. Blood and muscle biopsy samples were obtained before and after training. After training muscle CSA of the femoral region, 1RM for bench‐press and leg‐press, muscular endurance, and skeletal muscle VEGF protein levels significantly increased in both groups. The increase in muscular endurance was significantly higher in the HRT group. Plasma VEGF concentration and skeletal muscle capillary‐to‐fiber ratio were significantly higher in the HRT group than the NRT group following training. Our results suggest that, in addition to increases in muscle size and strength, HRT may also lead to increased muscular endurance and the promotion of angiogenesis in skeletal muscle. PMID:24907297

  17. Genetics Home Reference: spinal and bulbar muscular atrophy

    MedlinePlus

    ... from a particular type of mutation in the AR gene. This gene provides instructions for making a ... as regulating hair growth and sex drive. The AR gene mutation that causes spinal and bulbar muscular ...

  18. Gay male attraction toward muscular men: does mating context matter?

    PubMed

    Varangis, Eleanna; Lanzieri, Nicholas; Hildebrandt, Tom; Feldman, Matthew

    2012-03-01

    The purpose of this study was to examine gay men's perceived attractiveness of male figures based on short-term and long-term partner contexts. A sample of 190 gay adult men rated the attractiveness of line-drawings depicting male figures varying systematically in muscularity and body fat percentage in both short-term and long-term dating contexts. Mixed effects modeling was used to estimate the effects of figure (muscularity and body fat), dating context (short-term vs. long-term), and individual rater characteristics on attractiveness ratings. Results indicated that figure muscularity and body-fat had significant non-linear (i.e., quadratic) relationships with attractiveness ratings, and short-term dating context was associated with more discriminating ratings of attractiveness. Interactions between individual characteristics and figure characteristics indicated that the more available the individual and lower body fat, the more discriminating they were in ratings of attractiveness. The implications for future investigations considering both object and observer characteristics of attractiveness preferences are discussed. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. Adaptability and Prediction of Anticipatory Muscular Activity Parameters to Different Movements in the Sitting Position.

    PubMed

    Chikh, Soufien; Watelain, Eric; Faupin, Arnaud; Pinti, Antonio; Jarraya, Mohamed; Garnier, Cyril

    2016-08-01

    Voluntary movement often causes postural perturbation that requires an anticipatory postural adjustment to minimize perturbation and increase the efficiency and coordination during execution. This systematic review focuses specifically on the relationship between the parameters of anticipatory muscular activities and movement finality in sitting position among adults, to study the adaptability and predictability of anticipatory muscular activities parameters to different movements and conditions in sitting position in adults. A systematic literature search was performed using PubMed, Science Direct, Web of Science, Springer-Link, Engineering Village, and EbscoHost. Inclusion and exclusion criteria were applied to retain the most rigorous and specific studies, yielding 76 articles, Seventeen articles were excluded at first reading, and after the application of inclusion and exclusion criteria, 23 were retained. In a sitting position, central nervous system activity precedes movement by diverse anticipatory muscular activities and shows the ability to adapt anticipatory muscular activity parameters to the movement direction, postural stability, or charge weight. In addition, these parameters could be adapted to the speed of execution, as found for the standing position. Parameters of anticipatory muscular activities (duration, order, and amplitude of muscle contractions constituting the anticipatory muscular activity) could be used as a predictive indicator of forthcoming movement. In addition, this systematic review may improve methodology in empirical studies and assistive technology for people with disabilities. © The Author(s) 2016.

  20. Proximal muscular atrophy and weakness: An unusual adverse effect of deferasirox iron chelation therapy.

    PubMed

    Vill, K; Müller-Felber, W; Teusch, V; Blaschek, A; Gerstl, L; Huetker, S; Albert, M H

    2016-01-01

    Deferasirox is a standard treatment for chronic transfusional iron overload. Adverse effects of deferasirox have been reported in large prospective studies. We report two cases of monozygotic twins manifesting with proximal muscular atrophy and weakness under deferasirox. Discontinuation of deferasirox resulted in symptom improvement and ultimately in complete remission five months after successful haematopoietic stem cell transplantation. Broad diagnostic work-up could not bring evidence of another aetiology of muscular weakness. Iron overload or beta thalassemia itself as a cause is considered unlikely in our patients because the chronological coincidence of muscular symptoms was contra-directional to serum ferritin levels and significant clinical improvement was observed promptly after cessation of deferasirox even before transplantation. These observations suggest that the development of muscular weakness in patients on deferasirox should be recognised as a possible adverse effect of the drug. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Muscular dystrophy in the Japanese Spitz: an inversion disrupts the DMD and RPGR genes.

    PubMed

    Atencia-Fernandez, Sabela; Shiel, Robert E; Mooney, Carmel T; Nolan, Catherine M

    2015-04-01

    An X-linked muscular dystrophy, with deficiency of full-length dystrophin and expression of a low molecular weight dystrophin-related protein, has been described in Japanese Spitz dogs. The aim of this study was to identify the causative mutation and develop a specific test to identify affected cases and carrier animals. Gene expression studies in skeletal muscle of an affected animal indicated aberrant expression of the Duchenne muscular dystrophy (dystrophin) gene and an anomaly in intron 19 of the gene. Genome-walking experiments revealed an inversion that interrupts two genes on the X chromosome, the Duchenne muscular dystrophy gene and the retinitis pigmentosa GTPase regulator gene. All clinically affected dogs and obligate carriers that were tested had the mutant chromosome, and it is concluded that the inversion is the causative mutation for X-linked muscular dystrophy in the Japanese Spitz breed. A PCR assay that amplifies mutant and wild-type alleles was developed and proved capable of identifying affected and carrier individuals. Unexpectedly, a 7-year-old male animal, which had not previously come to clinical attention, was shown to possess the mutant allele and to have a relatively mild form of the disease. This observation indicates phenotypic heterogeneity in Japanese Spitz muscular dystrophy, a feature described previously in humans and Golden Retrievers. With the availability of a simple, fast and accurate test for Japanese Spitz muscular dystrophy, detection of carrier animals and selected breeding should help eliminate the mutation from the breed. © 2015 Stichting International Foundation for Animal Genetics.

  2. Aerobic fitness, muscular strength and obesity in relation to risk of heart failure.

    PubMed

    Crump, Casey; Sundquist, Jan; Winkleby, Marilyn A; Sundquist, Kristina

    2017-11-01

    Low physical fitness and obesity have been associated with higher risk of developing heart failure (HF), but their interactive effects are unknown. Elucidation of interactions among these common modifiable factors may help facilitate more effective primary prevention. We conducted a national cohort study to examine the interactive effects of aerobic fitness, muscular strength and body mass index (BMI) among 1 330 610 military conscripts in Sweden during 1969-1997 (97%-98% of all 18-year-old men) on risk of HF identified from inpatient and outpatient diagnoses through 2012 (maximum age 62 years). There were 11 711 men diagnosed with HF in 37.8 million person-years of follow-up. Low aerobic fitness, low muscular strength and obesity were independently associated with higher risk of HF, after adjusting for each other, socioeconomic factors, other chronic diseases and family history of HF. The combination of low aerobic fitness and low muscular strength (lowest vs highest tertiles) was associated with a 1.7-fold risk of HF (95% CI 1.6 to 1.9; p<0.001; incidence rates per 100 000 person-years, 43.2 vs 10.8). These factors had positive additive and multiplicative interactions (p<0.001) and were associated with increased risk of HF even among men with normal BMI. Low aerobic fitness, low muscular strength and obesity at the age of 18 years were independently associated with higher risk of HF in adulthood, with interactive effects between aerobic fitness and muscular strength. These findings suggest that early-life interventions may help reduce the long-term risk of HF and should include both aerobic fitness and muscular strength, even among persons with normal BMI. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  3. Muscular strength and incident hypertension in normotensive and prehypertensive men.

    PubMed

    Maslow, Andréa L; Sui, Xuemei; Colabianchi, Natalie; Hussey, Jim; Blair, Steven N

    2010-02-01

    The protective effects of cardiorespiratory fitness (CRF) on hypertension (HTN) are well known; however, the association between muscular strength and incidence of HTN has yet to be examined. This study evaluated the strength-HTN association with and without accounting for CRF. Participants were 4147 men (age = 20-82 yr) in the Aerobics Center Longitudinal Study for whom an age-specific composite muscular strength score was computed from measures of a one-repetition maximal leg and a one-repetition maximal bench press. CRF was quantified by maximal treadmill exercise test time in minutes. Cox proportional hazards regression analysis was used to estimate hazard ratios (HR) and 95% confidence intervals of incident HTN events according to exposure categories. During a mean follow-up of 19 yr, there were 503 incident HTN cases. Multivariable-adjusted (excluding CRF) HR of HTN in normotensive men comparing middle- and high-strength thirds to the lowest third were not significant at 1.17 and 0.84, respectively. Multivariable-adjusted (excluding CRF) HR of HTN in baseline prehypertensive men comparing middle- and high-strength thirds to the lowest third were significant at 0.73 and 0.72 (P = 0.01 each), respectively. The association between muscular strength and incidence of HTN in baseline prehypertensive men was no longer significant after control for CRF (P = 0.26). The study indicated that middle and high levels of muscular strength were associated with a reduced risk of HTN in prehypertensive men only. However, this relationship was no longer significant after controlling for CRF.

  4. Muscular Strength and Incident Hypertension in Normotensive and Prehypertensive Men

    PubMed Central

    Maslow, Andréa L.; Sui, Xuemei; Colabianchi, Natalie; Hussey, Jim; Blair, Steven N.

    2009-01-01

    The protective effects of cardiorespiratory fitness (CRF) on hypertension (HTN) are well known; however, the association between muscular strength and incidence of HTN has yet to be examined. Purpose This study evaluated the strength-HTN association with and without accounting for CRF. Methods Participants were 4147 men (20–82 years) in the Aerobics Center Longitudinal Study for whom an age-specific composite muscular strength score was computed from measures of a 1-repetition maximal leg and a 1-repetition maximal bench press. CRF was quantified by maximal treadmill exercise test time in minutes. Cox proportional hazards regression analysis was used to estimate hazard ratios (HRs) and 95% confidence intervals of incident HTN events according to exposure categories. Results During a mean follow-up of 19 years, there were 503 incident HTN cases. Multivariable-adjusted (excluding CRF) HRs of hypertension in normotensive men comparing middle and high strength thirds to the lowest third were not significant at 1.17 and 0.84, respectively. Multivariable-adjusted (excluding CRF) HRs of hypertension in baseline prehypertensive men comparing middle and high strength thirds to the lowest third were significant at 0.73 and 0.72 (p=.01 each), respectively. The association between muscular strength and incidence of HTN in baseline prehypertensive men was no longer significant after control for CRF (p=.26). Conclusions The study indicated that middle and high levels of muscular strength were associated with a reduced risk of HTN in prehypertensive men only. However, this relationship was no longer significant after controlling for CRF. PMID:19927030

  5. [Muscular disorders associated with ankylosing spondylitis and their correction with the help of whole body cryotherapy].

    PubMed

    Kulikov, A G; Tabiev, V I; Rassulova, M A

    2015-01-01

    The objective of the present study was to evaluate the possibilities for the correction of muscular disorders associated with ankylosing spondylitis and their correction with the help of whole body cryotherapy. The study included 55 patients randomly allocated to two groups. Group 1 was comprised of the patients treated with the use of the common mineral baths, physiotherapy, therapeutic physical exercises, spinal massage, and whole body air-cryotherapy. Group 2 contained the patients who were treated in a similar way with the exception of whole body cryotherapy; they served as controls. Muscular disorders were diagnosed by means of functional muscular testing. The study has demonstrated the high prevalence of muscular disorders in the patients suffering from ankylosing spondylitis. Moreover, it revealed the profile of such disorders associated with ankylosing spondylitis and showed significant correlation between the results of functional muscular testing, BASMI and BASFI indices as well as characteristics of chest excursions (p<0.01). The analysis of the results of the treatment gave evidence of the higher effectiveness of the combined treatment including whole body cryotherapy in comparison with the alternative therapeutic modalities employed in the present study. This therapeutic modality ensured the statistically more pronounced improvement of functional muscular testing parameters (p<0.05), muscle strength and extensibility, as well as certain other clinical and functional characteristics. The groups of muscles most susceptible to cryogenic therapy have been identified. The data obtained in the present study shed light on some specific features of the action of whole body cryotherapy accounting for its corrective influence on the muscular disorders in the patients presenting with ankylosing spondylitis. It is concluded that the proposed approach can be recommended for the introduction in the combined therapeutic and rehabilitative treatment of muscular

  6. The importance of genetic diagnosis for Duchenne muscular dystrophy

    PubMed Central

    Aartsma-Rus, Annemieke; Ginjaar, Ieke B; Bushby, Kate

    2016-01-01

    Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy are caused by mutations in the dystrophin-encoding DMD gene. Large deletions and duplications are most common, but small mutations have been found as well. Having a correct diagnosis is important for family planning and providing proper care to patients according to published guidelines. With mutation-specific therapies under development for DMD, a correct diagnosis is now also important for assessing whether patients are eligible for treatments. This review discusses different mutations causing DMD, diagnostic techniques available for making a genetic diagnosis for children suspected of DMD and the importance of having a specific genetic diagnosis in the context of emerging genetic therapies for DMD. PMID:26754139

  7. Feeling Abnormal: Simulation of Deviancy in Abnormal and Exceptionality Courses.

    ERIC Educational Resources Information Center

    Fernald, Charles D.

    1980-01-01

    Describes activity in which student in abnormal psychology and psychology of exceptional children classes personally experience being judged abnormal. The experience allows the students to remember relevant research, become sensitized to the feelings of individuals classified as deviant, and use caution in classifying individuals as abnormal.…

  8. Abnormal Uterine Bleeding

    MedlinePlus

    ... abnormal uterine bleeding? Abnormal uterine bleeding is any heavy or unusual bleeding from the uterus (through your ... one symptom of abnormal uterine bleeding. Having extremely heavy bleeding during your period can also be considered ...

  9. Reversible neuronal and muscular toxicity of caffeine in developing vertebrates.

    PubMed

    Rodriguez, Rufino S; Haugen, Rebecca; Rueber, Alexandra; Huang, Cheng-Chen

    2014-06-01

    This study utilizes zebrafish embryos to understand the cellular and molecular mechanisms of caffeine toxicity in developing vertebrate embryos. By using a high concentration of caffeine, we observed almost all the phenotypes that have been described in humans and/or in other animal models, including neural tube closure defect, jittery, touch insensitivity, and growth retardation as well as a drastic coiled body phenotype. Zebrafish embryos exposed to 5mM caffeine exhibited high frequent movement, 10 moves/min comparing with around 3 moves/min in control embryos, within half an hour post exposure (HPE). They later showed twitching, uncoordinated movement, and eventually severe body curvature by 6HPE. Exposure at later stages resulted in the same phenotypes but more posteriorly. Surprisingly, when caffeine was removed before 6HPE, the embryos were capable of recovering but still exhibited mild curvature and shorter bodies. Longer exposure caused irreversible body curvature and lethality. These results suggest that caffeine likely targets the neuro-muscular physiology in developing embryos. Immunohistochemistry revealed that the motorneurons in treated embryos developed shorter axons, abnormal branching, and excessive synaptic vesicles. Developing skeletal muscles also appeared smaller and lacked the well-defined boundaries seen in control embryos. Finally, caffeine increases the expression of genes involved in synaptic vesicle migration. In summary, our results provide molecular understanding of caffeine toxicity on developing vertebrate embryos. Published by Elsevier Inc.

  10. Temporalis muscle hypertrophy and reduced skull eccentricity in Duchenne muscular dystrophy.

    PubMed

    Straathof, C S M; Doorenweerd, N; Wokke, B H A; Dumas, E M; van den Bergen, J C; van Buchem, M A; Hendriksen, J G M; Verschuuren, J J G M; Kan, H E

    2014-10-01

    Muscle hypertrophy and muscle weakness are well known in Duchenne muscular dystrophy. Decreased muscle force can have secondary effects on skeletal growth and development such as facial and dental morphology changes. In this study, we quantified temporal muscle thickness, circumference, and eccentricity of the skull and the head on T1-weighted magnetic resonance imaging (MRI) scans of the head of 15 Duchenne muscular dystrophy patients and 15 controls. Average temporal muscle thickness was significantly increased in patients (12.9 ± 5.2 mm) compared to controls (6.8 ± 1.4 mm) (P < .0001), whereas the shape of the skull was significantly rounder compared to controls. Temporal muscle thickness and skull eccentricity were significantly negatively correlated in patients, and positively in controls. Hypertrophy of the temporal muscles and changes in skull eccentricity appear to occur early in the course of Duchenne muscular dystrophy. Further studies in younger patients are needed to confirm a causal relationship. © The Author(s) 2014.

  11. The muscular force transmission system: role of the intramuscular connective tissue.

    PubMed

    Turrina, Andrea; Martínez-González, Miguel Antonio; Stecco, Carla

    2013-01-01

    The objective of this review is to analyze in detail the microscopic structure and relations among muscular fibers, endomysium, perimysium, epimysium and deep fasciae. In particular, the multilayer organization and the collagen fiber orientation of these elements are reported. The endomysium, perimysium, epimysium and deep fasciae have not just a role of containment, limiting the expansion of the muscle with the disposition in concentric layers of the collagen tissue, but are fundamental elements for the transmission of muscular force, each one with a specific role. From this review it appears that the muscular fibers should not be studied as isolated elements, but as a complex inseparable from their fibrous components. The force expressed by a muscle depends not only on its anatomical structure, but also the angle at which its fibers are attached to the intramuscular connective tissue and the relation with the epimysium and deep fasciae. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. Management of cardiac involvement in muscular dystrophies: paediatric versus adult forms.

    PubMed

    Palladino, Alberto; D'Ambrosio, Paola; Papa, Andrea Antonio; Petillo, Roberta; Orsini, Chiara; Scutifero, Marianna; Nigro, Gerardo; Politano, Luisa

    2016-12-01

    Muscular dystrophies are a group of genetic disorders characterized by muscle degeneration and consequent substitution by fat and fibrous tissue. Cardiac involvement is an almost constant feature in a great part of these diseases, as both primary myocardial involvement and secondary involvement due to respiratory insufficiency, pulmonary hypertension or reduced mobility. Primary myocardial involvement usually begins more precociously compared to the secondary involvement. In fact the first signs of cardiomyopathy can be observed in the first decade of life in muscular dystrophies with childhood onset and later in adult form of muscular dystrophies as myotonic dystrophy type 1. At least an annual cardiac follow-up is recommended in these patients including clinical and instrumental examination (ECG, 24h Holter monitoring, ECHO), to detect cardiac involvement. A more frequent monitoring may be required according to the type of cardiomyopathy and the patient's needs. In this short review practical guide-lines are shown for physicians routinely involved in the management of these patients.

  13. Prenatal molecular diagnosis of inherited neuromuscular diseases: Duchenne/Becker muscular dystrophy, myotonic dystrophy type 1 and spinal muscular atrophy.

    PubMed

    Esposito, Gabriella; Ruggiero, Raffaella; Savarese, Maria; Savarese, Giovanni; Tremolaterra, Maria Roberta; Salvatore, Francesco; Carsana, Antonella

    2013-12-01

    Neuromuscular disease is a broad term that encompasses many diseases that either directly, via an intrinsic muscle disorder, or indirectly, via a nerve disorder, impairs muscle function. Here we report the experience of our group in the counselling and molecular prenatal diagnosis of three inherited neuromuscular diseases, i.e., Duchenne/Becker muscular dystrophy (DMD/BMD), myotonic dystrophy type 1 (DM1), spinal muscular atrophy (SMA). We performed a total of 83 DMD/BMD, 15 DM1 and 54 SMA prenatal diagnoses using a combination of technologies for either direct or linkage diagnosis. We identified 16, 5 and 10 affected foetuses, respectively. The improvement of analytical procedures in recent years has increased the mutation detection rate and reduced the analytical time. Due to the complexity of the experimental procedures and the high, specific professional expertise required for both laboratory activities and the related counselling, these types of analyses should be preferentially performed in reference molecular diagnostic centres.

  14. Molecular Signatures of Membrane Protein Complexes Underlying Muscular Dystrophy*

    PubMed Central

    Turk, Rolf; Hsiao, Jordy J.; Smits, Melinda M.; Ng, Brandon H.; Pospisil, Tyler C.; Jones, Kayla S.; Campbell, Kevin P.; Wright, Michael E.

    2016-01-01

    Mutations in genes encoding components of the sarcolemmal dystrophin-glycoprotein complex (DGC) are responsible for a large number of muscular dystrophies. As such, molecular dissection of the DGC is expected to both reveal pathological mechanisms, and provides a biological framework for validating new DGC components. Establishment of the molecular composition of plasma-membrane protein complexes has been hampered by a lack of suitable biochemical approaches. Here we present an analytical workflow based upon the principles of protein correlation profiling that has enabled us to model the molecular composition of the DGC in mouse skeletal muscle. We also report our analysis of protein complexes in mice harboring mutations in DGC components. Bioinformatic analyses suggested that cell-adhesion pathways were under the transcriptional control of NFκB in DGC mutant mice, which is a finding that is supported by previous studies that showed NFκB-regulated pathways underlie the pathophysiology of DGC-related muscular dystrophies. Moreover, the bioinformatic analyses suggested that inflammatory and compensatory mechanisms were activated in skeletal muscle of DGC mutant mice. Additionally, this proteomic study provides a molecular framework to refine our understanding of the DGC, identification of protein biomarkers of neuromuscular disease, and pharmacological interrogation of the DGC in adult skeletal muscle https://www.mda.org/disease/congenital-muscular-dystrophy/research. PMID:27099343

  15. Discontinuation of statin therapy due to muscular side effects: a survey in real life.

    PubMed

    Rosenbaum, D; Dallongeville, J; Sabouret, P; Bruckert, E

    2013-09-01

    To assess the burden of statin related muscular symptom in real life. We conducted a wide survey on 10,409 French subjects. Among these, 2850 (27%) had hypercholesterolemia and 1074 were treated with statins. Muscular symptoms were reported by 104 (10%) statin treated patients and led to discontinuation in 30% of the symptomatic patients. The main prescribed statins were low doses rosuvastatin, atorvastatin and simvastatin. Pains were the most commonly described symptoms (87%) but many patients also reported stiffness (62%), cramps (67%), weakness or a loss of strength during exertion (55%). Pain was localized in 70% but mostly described as affecting several muscular groups. Approximately 38% of patients reported that their symptoms prevented even moderate exertion during everyday activities, while 42% of patients suffered major disruption to their everyday life. Muscular symptoms associated with average dosage statin therapy are more frequent than in clinical trials and have a greater impact on patients' life than usually thought. Copyright © 2012 Elsevier B.V. All rights reserved.

  16. Muscular imbalance and shoulder pain in volleyball attackers.

    PubMed Central

    Kugler, A; Krüger-Franke, M; Reininger, S; Trouillier, H H; Rosemeyer, B

    1996-01-01

    OBJECTIVE: In overhead sports such as volleyball, baseball, or tennis shoulder problems are very common. The aim of this study was to identify features which may correlate with shoulder problems in volleyball attackers. METHODS: 30 competitive volleyball attackers (mean age 25 years) were included in the study; 15 were suffering from shoulder pain and 15 had no history of shoulder pain. The results were compared with those of a control group of 15 recreational athletes without any overhead sports activities. RESULTS: Volleyball attackers have a different muscular and capsular pattern at the playing shoulder compared to the opposite shoulder. Their playing shoulder is depressed, the scapula lateralised, and the dorsal muscles and the posterior and inferior part of the shoulder capsule shortened. These differences were of more significance in volleyball attackers with shoulder pain than in volleyball players without shoulder pain. In contrast to recreational athletes without any overhead sports activity, there were no significant difference in the comparison of the two shoulders. The histories, clinical and sonographic findings did not reveal further typical features for volleyball attackers with shoulder pain. CONCLUSIONS: Muscular balance of the shoulder girdle is very important in this sport. It is therefore imperative to include adequate stretching and muscular training programme for the prevention, as well as for therapy, of shoulder pain in volleyball attackers. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:8889124

  17. Reduction of low back muscular discomfort through an applied ergonomics intervention program.

    PubMed

    Poosanthanasarn, Nitaya; Sriboorapa, Sooth; Fungladda, Wijitr; Lohachit, Chantima

    2005-01-01

    An applied ergonomics intervention program (AEIP) was conducted with male employees who work in the pressing and storage sections of a metal auto parts factory in eastern Thailand. The objective of this study was to reduce worker muscular discomfort at the low back. The study design was a participatory research approach, with quasi-experimental pretest-posttest, and with a non-equivalent control group. Thirty-five persons participated in the AEIP (AEIP group) and 17 persons did not (non-AEIP group). The AEIP was composed of three major categories: (1) top management support; (2) equipment designed for workstations and manual material handling; and (3) administrative intervention, training, and health education. Muscle activity was measured by surface electromyography of the left and right erector spinae, and multifidus muscles; and evaluated by multivariate test for dependent samples (paired observation) and for independent samples. After the AEIP, the low back muscular loads of the AEIP group was significantly reduced, while those of the non-AEIP group were not. Comparison of the means of percentage maximum voluntary contractions (% MVC) of low back muscular activity between the AEIP group and non-AEIP group indicated that the AEIP group had significantly reduced low back muscular load, with a 95% confidence level (p-value < 0.05).

  18. Sexuality and the drive for muscularity: evidence of associations among British men.

    PubMed

    Swami, Viren; Diwell, Rachel; McCreary, Donald R

    2014-09-01

    Previous studies have documented associations between sexuality and body image, but the directionality of this association is unclear among men. This study examined whether men's drive for muscularity can be considered a correlate of their sexuality. A community-based sample of 292 heterosexual men from London, UK, completed a survey consisting of measures of drive for muscularity, sociosexuality, sexual assertiveness, sexual esteem, and sexual sensation seeking. A multiple regression analysis showed that greater drive for muscularity was predicted by more unrestricted sociosexuality (i.e., a greater proclivity for short-term, transient relationships), greater sexual sensation seeking, and greater sexual assertiveness, once the effects of participant age and body mass index had been accounted for. Possible avenues for intervention based on a sex-positive approach are discussed in conclusion. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Developmental Defects in a Zebrafish Model for Muscular Dystrophies Associated with the Loss of Fukutin-Related Protein (FKRP)

    ERIC Educational Resources Information Center

    Thornhill, Paul; Bassett, David; Lochmuller, Hanns; Bushby, Kate; Straub, Volker

    2008-01-01

    A number of muscular dystrophies are associated with the defective glycosylation of [alpha]-dystroglycan and many are now known to result from mutations in a number of genes encoding putative or known glycosyltransferases. These diseases include severe forms of congenital muscular dystrophy (CMD) such as Fukuyama type congenital muscular dystrophy…

  20. Ectopic Expression of Retrotransposon-Derived PEG11/RTL1 Contributes to the Callipyge Muscular Hypertrophy

    PubMed Central

    Xu, Xuewen; Ectors, Fabien; Davis, Erica E.; Pirottin, Dimitri; Cheng, Huijun; Farnir, Frédéric; Hadfield, Tracy; Cockett, Noelle; Charlier, Carole; Georges, Michel; Takeda, Haruko

    2015-01-01

    The callipyge phenotype is an ovine muscular hypertrophy characterized by polar overdominance: only heterozygous + Mat /CLPG Pat animals receiving the CLPG mutation from their father express the phenotype. + Mat /CLPG Pat animals are characterized by postnatal, ectopic expression of Delta-like 1 homologue (DLK1) and Paternally expressed gene 11/Retrotransposon-like 1 (PEG11/RTL1) proteins in skeletal muscle. We showed previously in transgenic mice that ectopic expression of DLK1 alone induces a muscular hypertrophy, hence demonstrating a role for DLK1 in determining the callipyge hypertrophy. We herein describe newly generated transgenic mice that ectopically express PEG11 in skeletal muscle, and show that they also exhibit a muscular hypertrophy phenotype. Our data suggest that both DLK1 and PEG11 act together in causing the muscular hypertrophy of callipyge sheep. PMID:26474044

  1. A Rare Case Report of Neurodegenerative Disease: Duchenne Muscular Dystrophy in Two Male Siblings

    PubMed Central

    Suneja, B; Suneja, ES; Chandna, P

    2015-01-01

    ABSTRACT Duchenne muscular dystrophy (DMD) is an recessive X-linked mediated, musculoskeletal disorder that affects only males. It is the most common and severe form of muscular dystrophy where there is failure to manufacture dystrophin. Clinically, it is characterized by progressive muscle wasting eventually leading to premature death. This case report describes the genetic, oral and systemic findings in two cases of DMD in male siblings. How to cite this article: Suneja B, Suneja ES, Adlakha VK, Chandna P. A Rare Case Report of Neurodegenerative Disease: Duchenne Muscular Dystrophy in Two Male Siblings. Int J Clin Pediatr Dent 2015;8(2):163-165. PMID:26379389

  2. Muscular hypertrophy of the left diaphragmatic crus: an unusual cause of a paraspinal "mass".

    PubMed

    Woodring, J H; Bognar, B

    1998-04-01

    We present a case of marked muscular hypertrophy of the muscular portion of the diaphragm and of the diaphragmatic crura in a professional opera singer. In this case the right and left crus each measured 20 mm in maximum thickness. The left crus, by nature of its vertical orientation in the sagittal plane, produced marked deviation of the inferior left paraspinal line near the diaphragm mimicking a retrocrural or paraspinal mass on the posteroanterior chest radiograph. The correct diagnosis was made by computed tomography. Muscular hypertrophy of the diaphragmatic crura should be included in the differential diagnosis of retrocrural or paraspinal masses at the level of the diaphragm.

  3. Central nervous system abnormalities in vaginismus.

    PubMed

    Frasson, Emma; Graziottin, Alessandra; Priori, Alberto; Dall'ora, Elisa; Didonè, Giuseppe; Garbin, Emilio Luigi; Vicentini, Silvana; Bertolasi, Laura

    2009-01-01

    To investigate possible altered CNS excitability in vaginismus. In 10 patients with primary idiopathic lifelong vaginismus, 10 with vulvar vestibulitis syndrome accompanied by vaginismus and healthy controls we recorded EMG activity from the levator ani (LA) and external anal sphincter (EAS) muscles and tested bulbocavernosus reflex (BCR). Pudendal-nerve somatosensory evoked potentials (SEPs) were tested after a single stimulus. Pudendal-nerve SEP recovery functions were assessed using a paired conditioning-test paradigm at interstimulus intervals (ISIs) of 5, 20 and 40ms. EMG in patients showed muscular hyperactivity at rest and reduced inhibition during straining. The BCR polysynaptic R2 had larger amplitude (p<0.01) and longer duration (p<0.01) in patients from both groups than in controls. In controls, paired-pulse SEPs were suppressed at the 5ms ISI for N35-P40 (p<0.05) and P40-N50 ms (p<0.001) and facilitated at the 20ms ISI for N35-P40 (p<0.05) and P40-N50 (p<0.05). No significant differences were found in the paired-pulse N35-P40 in patients and controls but the cortical P40-N50 at 20 ISI was facilitated in patients (p<0.05). EMG activity is enhanced and the cortical SEP recovery cycle and BCR are hyperexcitable in vaginismus. The neurophysiological abnormalities in patients with vaginismus indicate concomitant CNS changes in this disorder.

  4. Visuospatial Attention Disturbance in Duchenne Muscular Dystrophy

    ERIC Educational Resources Information Center

    De Moura, Maria Clara Drummond Soares; do Valle, Luiz Eduardo Ribeiro; Resende, Maria Bernadete Dutra; Pinto, Katia Osternack

    2010-01-01

    Aim: The cognitive deficits present in the Duchenne muscular dystrophy (DMD) are not yet well characterized. Attention, considered to be the brain mechanism responsible for the selection of sensory stimuli, could be disturbed in DMD, contributing, at least partially, to the observed global cognitive deficit. The aim of this study was to…

  5. Effect of a core conditioning intervention on tests of trunk muscular endurance in school-aged children.

    PubMed

    Allen, Brett A; Hannon, James C; Burns, Ryan D; Williams, Skip M

    2014-07-01

    Trunk and core muscular development has been advocated to increase athletic performance and for maintenance of musculoskeletal health, especially related to the prevention of low back pain (LBP). The purpose of this study was to examine the effects of a simple core conditioning routine on tests of trunk and core muscular endurance in school-aged children. Participants included 164 students (86 girls, 78 boys; mean age, 11.5 ± 2.5 years) recruited from a grade school in a metropolitan area located in the southwestern United States. Students performed an equipment-free, moderate-to-high intensity, dynamic core conditioning warm-up routine once a week for a period of 6 weeks during the start of their physical education classes. The intervention consisted of 10 different dynamic core conditioning exercises performed at a 30-second duration per exercise totaling 5 minutes per session. Pre- and post-assessments of muscular endurance consisted of 5 different trunk and core muscular endurance tests: Parallel Roman Chair Dynamic Back Extension, Prone Plank, Lateral Plank, Dynamic Curl-Up, and Static Curl-up. A generalized estimation equation was used to analyze differences in pre- and post-intervention muscular fitness assessments controlling for gender and grade level. Analysis of the data revealed significant increases in muscular fitness test performance for each of the 5 measured outcomes (p < 0.001). Because risk factors of LBP are thought to commence during childhood, results of this study suggest that it may be desirable for children and adolescents to perform moderate-to-high intensity dynamic core exercises during physical education warm-up to improve trunk and core muscular endurance.

  6. The pattern of abnormalities on sperm analysis: A study of 1186 infertile male in Yasmin IVF clinic Jakarta

    NASA Astrophysics Data System (ADS)

    Aulia, S. N.; Lestari, S. W.; Pratama, G.; Harzief, A. K.; Sumapraja, K.; Hestiantoro, A.; Wiweko, B.

    2017-08-01

    A declined in semen quality resulted an increase of male infertility has been reported. The pattern of abnormalities differs from one country to another. Conflicting results from different studies may be influenced by many factor. The aims are to evaluate the pattern of semen analysis of male partners of infertile couples and identify the current status of the contribution of male factor towards the infertility in our environment. The study is a descriptive analysis of the semen analysis of male partners in infertile couples, who were present at Yasmin IVF Clinic, infertility clinic of a Tertiary Care University Teaching Hospital between 1st January 2012 and 31st December 2015. A total of 1186 consenting male partners of infertile couple were recruited into the study. According to 2010 WHO normal reference values for semen parameters, 795 (67%) of patients were normozoospermia which had normal semen parameters and 391 (33%) patients had abnormal semen parameters. Oligozospermia was evident in 155 (39.5%) patients, being the most common disorder observed. It is followed by azoospermia (24.4%), oligoasthenozospermia (17.8%), asthenozospermia (5.9%), oligoasthenotera-tozospermia (5,7%), teratozospermia (2.6%), asthenoteratozospermia (2.8%), cryptozoospermia (0.8%), necrozospermia (0.3%), and oligoteratozospermia (0.3%). Abnormal semen quality remains a significant contribution to the overall infertility with oligozospermia being the most common semen quality abnormality. This condition is an indication for the need to focus on the prevention and management of male infertility. In addition, further studies are needed to address possible etiologies and treatment in order to improve fertility rates.

  7. A Human Pluripotent Stem Cell Model of Facioscapulohumeral Muscular Dystrophy-Affected Skeletal Muscles.

    PubMed

    Caron, Leslie; Kher, Devaki; Lee, Kian Leong; McKernan, Robert; Dumevska, Biljana; Hidalgo, Alejandro; Li, Jia; Yang, Henry; Main, Heather; Ferri, Giulia; Petek, Lisa M; Poellinger, Lorenz; Miller, Daniel G; Gabellini, Davide; Schmidt, Uli

    2016-09-01

    : Facioscapulohumeral muscular dystrophy (FSHD) represents a major unmet clinical need arising from the progressive weakness and atrophy of skeletal muscles. The dearth of adequate experimental models has severely hampered our understanding of the disease. To date, no treatment is available for FSHD. Human embryonic stem cells (hESCs) potentially represent a renewable source of skeletal muscle cells (SkMCs) and provide an alternative to invasive patient biopsies. We developed a scalable monolayer system to differentiate hESCs into mature SkMCs within 26 days, without cell sorting or genetic manipulation. Here we show that SkMCs derived from FSHD1-affected hESC lines exclusively express the FSHD pathogenic marker double homeobox 4 and exhibit some of the defects reported in FSHD. FSHD1 myotubes are thinner when compared with unaffected and Becker muscular dystrophy myotubes, and differentially regulate genes involved in cell cycle control, oxidative stress response, and cell adhesion. This cellular model will be a powerful tool for studying FSHD and will ultimately assist in the development of effective treatments for muscular dystrophies. This work describes an efficient and highly scalable monolayer system to differentiate human pluripotent stem cells (hPSCs) into skeletal muscle cells (SkMCs) and demonstrates disease-specific phenotypes in SkMCs derived from both embryonic and induced hPSCs affected with facioscapulohumeral muscular dystrophy. This study represents the first human stem cell-based cellular model for a muscular dystrophy that is suitable for high-throughput screening and drug development. ©AlphaMed Press.

  8. Effect of Movement Velocity During Resistance Training on Dynamic Muscular Strength: A Systematic Review and Meta-Analysis.

    PubMed

    Davies, Timothy B; Kuang, Kenny; Orr, Rhonda; Halaki, Mark; Hackett, Daniel

    2017-08-01

    Movement velocity is an acute resistance-training variable that can be manipulated to potentially optimize dynamic muscular strength development. However, it is unclear whether performing faster or slower repetitions actually influences dynamic muscular strength gains. We conducted a systematic review and meta-analysis to examine the effect of movement velocity during resistance training on dynamic muscular strength. Five electronic databases were searched using terms related to movement velocity and resistance training. Studies were deemed eligible for inclusion if they met the following criteria: randomized and non-randomized comparative studies; published in English; included healthy adults; used isotonic resistance-exercise interventions directly comparing fast or explosive training to slower movement velocity training; matched in prescribed intensity and volume; duration ≥4 weeks; and measured dynamic muscular strength changes. A total of 15 studies were identified that investigated movement velocity in accordance with the criteria outlined. Fast and moderate-slow resistance training were found to produce similar increases in dynamic muscular strength when all studies were included. However, when intensity was accounted for, there was a trend for a small effect favoring fast compared with moderate-slow training when moderate intensities, defined as 60-79% one repetition maximum, were used (effect size 0.31; p = 0.06). Strength gains between conditions were not influenced by training status and age. Overall, the results suggest that fast and moderate-slow resistance training improve dynamic muscular strength similarly in individuals within a wide range of training statuses and ages. Resistance training performed at fast movement velocities using moderate intensities showed a trend for superior muscular strength gains as compared to moderate-slow resistance training. Both training practices should be considered for novice to advanced, young and older

  9. Changes in muscular fitness and its association with blood pressure in adolescents.

    PubMed

    Agostinis-Sobrinho, César; Ruiz, Jonatan R; Moreira, Carla; Lopes, Luís; Ramírez-Vélez, Robinson; García-Hermoso, Antonio; Mota, Jorge; Santos, Rute

    2018-05-08

    The aims of this study were to examine the longitudinal association between muscular fitness (MF) and blood pressure (BP) 2 years later, and to determine whether changes in MF over a 2-year period were associated with BP at follow-up, in adolescents. The sample comprised 734 youths (349 girls) aged from 12 to 18 years. MF was assessed with the standing long jump and handgrip tests. Socioeconomic status, pubertal stage, waist circumference, resting BP, and cardiorespiratory fitness were measured according to standard procedures. Regression analyses showed a significant inverse association between MF at baseline and systolic BP (β = - 0.072; p = 0.032) and rate pressure product (β = - 0.124; p < 0.001) at follow-up, after adjustments for age, sex, height, pubertal stage, and socioeconomic status. However, when analyses were further adjusted for waist circumference and cardiorespiratory fitness, these associations did not remain significant. Adolescents with persistently high and increasing MF exhibited the lowest levels of diastolic BP (F (3, 721)  = 3.814, p = 0.018) and systolic BP (F (3, 721)  = 3.908, p = 0.014) when compared to those with persistent low MF after adjustment for age, sex, height, socioeconomic status, cardiorespiratory fitness, and waist circumference. This study suggests that persistent greater and increasing MF in youth are associated with lower levels of BP across the adolescence. What is Known: • Currently, there is a growing interest on the health benefits of muscular fitness. • Cross-sectional studies have identified an association between muscular fitness and blood pressure in adolescents. What is New: • Changes in muscular fitness during adolescence were associated with systolic and diastolic BP over a 2-year period. • Adolescents with persistently low muscular fitness exhibited the highest levels of diastolic and systolic BP.

  10. The Child with Muscular Dystrophy in School. Revised.

    ERIC Educational Resources Information Center

    Schock, Nancy C.

    Practical information on children with muscular dystrophy is intended to help parents and teachers facilitate their inclusion in mainstreamed classrooms. Major topics addressed include the following: transportation arrangements; providing full information to the teacher regarding the child's specific abilities and physical limitations;…

  11. Satellite Cells in Muscular Dystrophy - Lost in Polarity

    PubMed Central

    Chang, Natasha C.; Chevalier, Fabien P.; Rudnicki, Michael A.

    2016-01-01

    Recent findings employing the mdx mouse model for Duchenne muscular dystrophy (DMD) have revealed that muscle satellite stem cells play a direct role in contributing to disease etiology and progression of DMD, the most common and severe form of muscular dystrophy. Lack of dystrophin expression in DMD has critical consequences in satellite cells including an inability to establish cell polarity, abrogation of asymmetric satellite stem cell divisions and failure to enter the myogenic program. Thus, muscle wasting in dystrophic mice is not only caused by myofiber fragility, but is exacerbated by intrinsic satellite cell dysfunction leading to impaired regeneration. Despite intense research and clinical efforts, there is still no effective cure for DMD. In this review, we highlight recent research advances in DMD and discuss the current state of treatment and importantly, how we can incorporate satellite cell-targeted therapeutic strategies to correct satellite cell dysfunction in DMD. PMID:27161598

  12. Media exposure, mediated social comparison to idealized images of muscularity, and anabolic steroid use.

    PubMed

    Melki, Jad P; Hitti, Eveline A; Oghia, Michael J; Mufarrij, Afif A

    2015-01-01

    This study examined the association between anabolic-androgenic steroid (AAS) use and dominant sociocultural factors, specifically media exposure to idealized images of male muscularity, and mediated social comparison trends among a sample of young Arab adults. The study found evidence that participants more exposed to content that promotes muscularity and those who idealize images of muscularity and perceive them as motivators for achieving muscularity are more likely to be AAS users. It also found that a significant percentage of participants used at least one kind of dietary supplement and that the level of AAS use among health club participants indicates it is a significant public health problem in Lebanon. The study suggests that dealing with this problem requires a unique approach, beyond the typical awareness of risks strategy, since some users were well aware of the risks yet continue to use AAS, and their motivations pertain more to body image and sexuality. A stronger approach that utilizes critical media literacy teaching that ingrains these issues into school and university curricula will have a more lasting impact.

  13. Abnormal pressure study in the Malay and Penyu Basins: A regional understanding

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kader, M.S.; Leslie, W.

    1994-07-01

    A majority of wells drilled in the Malay and Penyu basins were terminated due to abnormal pressure. Blowouts and the subsequent loss of technical data have always been a concern during drilling operations. This study employs data from 94 exploratory wells spread throughout the Malay and Penyu basins. The postdrill abnormal pressure predictive method used is pressure vs. depth plots of data obtained from Repeat Formation tester (RFT) readings. The study results indicate that abnormal pressure occurs in a progressively older stratigraphic unit toward the basin margins. The margins of the Malay and the entire Penyu basins tend to bemore » normally pressured. The onset of abnormal pressure appears to be abrupt in the northern portion and more gradual in the southern part of the Malay Basin. Abnormal pressure in the Malay Basin is found to be neither depth dependent nor age related. Many factors can cause the abnormal formation pressures. In some areas, a combination of factors prevails. Rapid deposition of the middle to late Miocene siliciclastic sediments appears to be a dominant cause particularly in the center of the Malay Basin. A low sand:shale ratio coupled with a high geothermal gradient is also found to be a local cause near the axis of the basin. This phenomenon is crucial to the understanding of hydrocarbon migration and will enable the planning of safe and efficient drilling campaigns.« less

  14. Muscular system in the pacific bluefin tuna Thunnus orientalis (Teleostei: Scombridae).

    PubMed

    Nakae, Masanori; Sasaki, Kunio; Shinohara, Gento; Okada, Tokihiko; Matsuura, Keiichi

    2014-02-01

    The muscular system in the Pacific bluefin tuna Thunnus orientalis is studied in detail. For the first time, a complete description of the muscular anatomy of a thunnid is provided here. Eighty-two elements including subdivisions of components of the muscular system are identified. This is less than found in a basal perciform and two other investigated scombrid species, owing mainly to the absence or fusion of pectoral, pelvic and caudal fin muscles. The absence of elements of the basal perciform pattern was most prominent in the caudal fin, which includes only the flexor dorsalis, flexor ventralis, hypochordal longitudinalis, and interradialis. In the caudal fin, the medial fan-shaped ray was identified as the first dorsal ray, judging from myological and neuroanatomical characters. The highly developed gill filament muscles in Thunnus orientalis and sheet-like rectus communis control gill ventilation. Long body muscle tendons reduce the metabolic energy needed during rapid and continuous swimming. These characters are interpreted as adaptations in the context of the oceanic life style of the species. Copyright © 2013 Wiley Periodicals, Inc.

  15. Regulatory T cells suppress muscle inflammation and injury in muscular dystrophy

    PubMed Central

    Villalta, S. Armando; Rosenthal, Wendy; Martinez, Leonel; Kaur, Amanjot; Sparwasser, Tim; Tidball, James G.; Margeta, Marta; Spencer, Melissa J.; Bluestone, Jeffrey A.

    2016-01-01

    We examined the hypothesis that regulatory T cells (Tregs) modulate muscle injury and inflammation in the mdx mouse model of Duchenne muscular dystrophy (DMD). Although Tregs were largely absent in the muscle of wildtype mice and normal human muscle, they were present in necrotic lesions, displayed an activated phenotype and showed increased expression of interleukin (IL)-10 in dystrophic muscle from mdx mice. Depletion of Tregs exacerbated muscle injury and the severity of muscle inflammation, which was characterized by an enhanced interferon-gamma (IFNγ) response and activation of M1 macrophages. To test the therapeutic value of targeting Tregs in muscular dystrophy, we treated mdx mice with IL-2/anti-IL-2 complexes (IL-2c), and found that Tregs and IL-10 concentrations were increased in muscle, resulting in reduced expression of cyclooygenase-2 and decreased myofiber injury. These findings suggest that Tregs modulate the progression of muscular dystrophy by suppressing type 1 inflammation in muscle associated with muscle fiber injury, and highlight the potential of Treg-modulating agents as therapeutics for DMD. PMID:25320234

  16. [The muscular lesion in myasthenia gravis: study of 17 cases with muscular histochemistry].

    PubMed

    Werneck, L C

    1982-03-01

    A study of 17 muscle biopsies from patients with myasthenia gravis was done, using freshfrozen section and histochemistry tecnics. It was found 15 abnormal muscle biopsies. The most common abnormality were small dark angular fibers, excess of lipids droplets outside the muscle membrane, changes in fiber size and type II fiber atrophy. These findings suggested denervation in 11 biopsies, type II fiber atrophy in 7, linfocyte infiltration in 4, fiber necrosis with fagocitosis in 1 and 2 were normal. Was noted a direct correlation between the disease duration and the severity of the histological abnormality. Two patients had tymoma. Congenital myasthenia gravis, rheumatoid arthritis, intersticial hypertrophic neuritis, Hashimoto tireoiditis and concomitance of myasthenic syndrome was found once in different patients.

  17. Meiotic abnormalities

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    NONE

    1993-12-31

    Chapter 19, describes meiotic abnormalities. These include nondisjunction of autosomes and sex chromosomes, genetic and environmental causes of nondisjunction, misdivision of the centromere, chromosomally abnormal human sperm, male infertility, parental age, and origin of diploid gametes. 57 refs., 2 figs., 1 tab.

  18. Co-incidence of Turner syndrome and Duchenne muscular dystrophy - an important problem for the clinician.

    PubMed

    Kaczorowska, Ewa; Zimowski, Janusz; Cichoń-Kotek, Monika; Mrozińska, Agnieszka; Purzycka, Joanna; Wierzba, Jolanta; Limon, Janusz; Lipska-Ziętkiewicz, Beata S

    Turner syndrome is a relatively common chromosomal disorder which affects about one in 2000 live born females. Duchenne muscular dystrophy is an X-linked recessive disorder affecting 1:3600 live born males. Considering the above, the coexistence of these two diseases may occur only anecdotally. Here, we report a 4 ½ year-old female with classical 45,X Turner syndrome who also had Duchenne muscular dystrophy caused by a point mutation in the dystrophin gene (c.9055delG). The patient showed the typical phenotype of Turner syndrome including distinctive dysmorphic features (short neck, low posterior hairline, wide position of nipples), aortic coarctation and feet lymphedema. Besides, she presented with an unusually early beginning of muscular dystrophy symptoms with infantile-onset motor developmental delay, intellectual disability and early calf muscular hypertrophy. The coexistence of an X-linked recessive disorder should be considered in women affected by Turner syndrome presenting with additional atypical clinical features.

  19. Effects of oral ATP supplementation on anaerobic power and muscular strength.

    PubMed

    Jordan, Alexander N; Jurca, Radim; Abraham, Edward H; Salikhova, Anna; Mann, Julia K; Morss, Gina M; Church, Timothy S; Lucia, Alejandro; Earnest, Conrad P

    2004-06-01

    We examined 14 d of oral adenosine 5'-triphosphate (ATP) supplementation on indices of anaerobic capacity and muscular strength. Twenty-seven healthy males successfully completed the trial, after randomly receiving in a double-blind manner an oral dose of low dose (150 mg) or high dose (225 mg) ATP, or matched placebo. To improve absorption characteristics, the ATP was enterically coated. Total blood ATP (whole blood and plasma ATP) concentrations, two Wingate anaerobic power tests (30 s), and muscular strength (1RM and three sets of repetitions to fatigue at 70% of 1RM) were measured under three conditions: (i) baseline; (ii) acutely (7d later, no prior supplementation and 75 min after ATP ingestion); and (iii) after 14 d of daily ingestion (post). Statistical analyses showed no significant between or within group treatment effects for whole blood ATP or plasma ATP concentrations for any treatment condition. We also did not observe any treatment effects for any Wingate testing parameter including peak PO, total work, average PO for 30 s, or post-Wingate lactate accumulation. Overall, we observed no significant between group treatment effects for any muscular strength parameter. We did observe several within group differences for the group ingesting the high ATP dosage including 1RM (6.6%; P < 0.04) and repetitions to fatigue during set 1 of posttesting (18.5%; P < 0.007) and total lifting volume at post (22%; P < 0.003). We conclude that enterically coated oral ATP supplementation may provide small ergogenic effects on muscular strength under some treatment conditions.

  20. Cathepsin S Contributes to the Pathogenesis of Muscular Dystrophy in Mice.

    PubMed

    Tjondrokoesoemo, Andoria; Schips, Tobias G; Sargent, Michelle A; Vanhoutte, Davy; Kanisicak, Onur; Prasad, Vikram; Lin, Suh-Chin J; Maillet, Marjorie; Molkentin, Jeffery D

    2016-05-06

    Duchenne muscular dystrophy (DMD) is an X-linked recessive disease caused by mutations in the gene encoding dystrophin. Loss of dystrophin protein compromises the stability of the sarcolemma membrane surrounding each muscle cell fiber, leading to membrane ruptures and leakiness that induces myofiber necrosis, a subsequent inflammatory response, and progressive tissue fibrosis with loss of functional capacity. Cathepsin S (Ctss) is a cysteine protease that is actively secreted in areas of tissue injury and ongoing inflammation, where it participates in extracellular matrix remodeling and healing. Here we show significant induction of Ctss expression and proteolytic activity following acute muscle injury or in muscle from mdx mice, a model of DMD. To examine the functional ramifications associated with greater Ctss expression, the Ctss gene was deleted in the mdx genetic background, resulting in protection from muscular dystrophy pathogenesis that included reduced myofiber turnover and histopathology, reduced fibrosis, and improved running capacity. Mechanistically, deletion of the Ctss gene in the mdx background significantly increased myofiber sarcolemmal membrane stability with greater expression and membrane localization of utrophin, integrins, and β-dystroglycan, which anchor the membrane to the basal lamina and underlying cytoskeletal proteins. Consistent with these results, skeletal muscle-specific transgenic mice overexpressing Ctss showed increased myofiber necrosis, muscle histopathology, and a functional deficit reminiscent of muscular dystrophy. Hence, Ctss induction during muscular dystrophy is a pathologic event that partially underlies disease pathogenesis, and its inhibition might serve as a new therapeutic strategy in DMD. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  1. Stem cell transplantation for treating Duchenne muscular dystrophy: A Web of Science-based literature analysis.

    PubMed

    Yang, Xiaofeng

    2012-08-05

    To identify global research trends in stem cell transplantation for treating Duchenne muscular dystrophy using a bibliometric analysis of Web of Science. We performed a bibliometric analysis of studies on stem cell transplantation for treating Duchenne muscular dystrophy from 2002 to 2011 retrieved from Web of Science. (a) peer-reviewed published articles on stem cell transplantation for treating Duchenne muscular dystrophy indexed in Web of Science; (b) original research articles, reviews, meeting abstracts, proceedings papers, book chapters, editorial material, and news items; and (c) publication between 2002 and 2011. (a) articles that required manual searching or telephone access; (b) documents that were not published in the public domain; and (c) corrected papers. (1) Annual publication output; (2) distribution according to subject areas; (3) distribution according to journals; (4) distribution according to country; (5) distribution according to institution; (6) distribution according to institution in China; (7) distribution according to institution that cooperated with Chinese institutions; (8) top-cited articles from 2002 to 2006; (9) top-cited articles from 2007 to 2011. A total of 318 publications on stem cell transplantation for treating Duchenne muscular dystrophy were retrieved from Web of Science from 2002 to 2011, of which almost half derived from American authors and institutes. The number of publications has gradually increased over the past 10 years. Most papers appeared in journals with a focus on gene and molecular research, such as Molecular Therapy, Neuromuscular Disorders, and PLoS One. The 10 most-cited papers from 2002 to 2006 were mostly about different kinds of stem cell transplantation for muscle regeneration, while the 10 most-cited papers from 2007 to 2011 were mostly about new techniques of stem cell transplantation for treating Duchenne muscular dystrophy. The publications on stem cell transplantation for treating Duchenne muscular

  2. BMI as a mediator of the relationship between muscular fitness and cardiometabolic risk in children: a mediation analysis.

    PubMed

    Díez-Fernández, Ana; Sánchez-López, Mairena; Gulías-González, Roberto; Notario-Pacheco, Blanca; Cañete García-Prieto, Jorge; Arias-Palencia, Natalia; Martínez-Vizcaíno, Vicente

    2015-01-01

    Muscular fitness levels have been associated with cardiometabolic risk in children, although whether body weight acts as a confounder or as an intermediate variable in this relationship remains controversial. The aim of this study was to examine whether the association between muscular fitness and cardiometabolic risk factors is mediated by body mass index (BMI). Cross-sectional study using a sample of 1158 schoolchildren aged 8-11 years from the province of Cuenca, Spain. We measured anthropometrics and biochemical variables and we calculated a muscular fitness index as the sum of z-scores of handgrip dynamometry/weight and standing long jump, and we estimated a previously validated cardiometabolic risk index (CMRI). Linear regression models were fitted for mediation analysis to assess whether the association between muscular fitness and cardiometabolic risk was mediated by BMI. Children with normal weight (NW) had a better cardiometabolic risk profile than their overweight (OW) or obese (OB) peers after controlling for muscular fitness. Marginal estimated mean ± SE values for NW, OW and OB categories of CMRI were -0.75 ± 0.06 < 0.84 ± 0.10 < 2.18 ± 0.16 in boys and -0.73 ± 0.06 < 0.96 ± 0.10 < 2.71 ± 0.17 in girls, both p < 0.001. Children with higher levels of muscular fitness had a better cardiometabolic risk profile (CMRI marginal estimated mean ± SE 1.04 ± 0.13 > 0.05 ± 0.09 >-1.16 ± 0.13 for lower, middle and upper quartiles of muscular fitness in boys and 1.01 ± 0.16 > 0.10 ± 0.09 > -1.02 ± 0.15 in girls, both p < 0.001), but differences disappeared when controlling for BMI. BMI acted as a full mediator between muscular fitness and most cardiometabolic risk factors (Sobel test z = -11.44 for boys; z = -11.83 for girls; p < 0.001 in CMRI mediation model) and as a partial mediator in the case of waist circumference (Sobel test z=-14.86 for boys; z=-14.51 for girls; p<0.001). BMI mediates the association between muscular fitness and

  3. [Percutaneous closure of ductus arteriosus and muscular ventricular defect with amplatzer occluder in a patient with severe pulmonary hypertension].

    PubMed

    García-Montes, José Antonio; Zabal Cerdeira, Carlos; Calderón-Colmenero, Juan; Espínola, Nilda; Fernández de la Reguera, Guillermo; Buendía Hernández, Alfonso

    2005-01-01

    Surgical treatment of multiple muscular ventricular septal defects with associated lesions and severe pulmonary hypertension has a high morbility and mortality. Closure of these defects by the Amplatzer muscular VSD occluder is an alternative to surgery, avoiding the need of cardiopulmonary bypass. We present the case of a 38 year-old woman with signs of heart failure in NYHA functional class IV, with two muscular ventricular septal defects, patent ductus arteriosus and severe pulmonary hypertension, that were treated with three Amplatzer muscular VSD occluders, with significant reduction of pulmonary pressure and functional class improvement.

  4. Prevalence and Characteristics of Chinese Patients With Duchenne and Becker Muscular Dystrophy

    PubMed Central

    Lo, Ivan F. M.; Cherk, Sharon W. W.; Cheng, Wai Wai; Fung, Eva L. W.; Yeung, Wai Lan; Ngan, Mary; Lee, Wing Cheong; Kwong, Ling; Wong, Suet Na; Ma, Che Kwan; Tai, Shuk Mui; Ng, Grace S. F.; Wu, Shun Ping; Wong, Virginia C. N.

    2015-01-01

    The aim of this collaborative study on Duchenne muscular dystrophy and Becker muscular dystrophy is to determine the prevalence and to develop data on such patients as a prelude to the development of registry in Hong Kong. Information on clinical and molecular findings, and patient care, was systematically collected in 2011 and 2012 from all Pediatric Neurology Units in Hong Kong. Ninety patients with dystrophinopathy were identified, and 83% has Duchenne muscular dystrophy. The overall prevalence of dystrophinopathy in Hong Kong in 2010 is 1.03 per 10 000 males aged 0 to 24 years. Among the Duchenne group, we observed a higher percentage (40.6%) of point mutations with a lower percentage (45.3%) of exon deletions in our patients when compared with overseas studies. Although we observed similar percentage of Duchenne group received scoliosis surgery, ventilation support, and cardiac treatment when compared with other countries, the percentage (25%) of steroid use is lower. PMID:28503591

  5. Genetic and Early Clinical Manifestations of Females Heterozygous for Duchenne/Becker Muscular Dystrophy.

    PubMed

    Papa, Riccardo; Madia, Francesca; Bartolomeo, Domenico; Trucco, Federica; Pedemonte, Marina; Traverso, Monica; Broda, Paolo; Bruno, Claudio; Zara, Federico; Minetti, Carlo; Fiorillo, Chiara

    2016-02-01

    Female carriers of Duchenne muscular dystrophy (DMD), although usually asymptomatic, develop muscle weakness up to 17% of the time, and a third present cardiac abnormalities or cognitive impairment. Clinical features of DMD carriers during childhood are poorly known. We describe a cohort of pediatric DMD carriers, providing clinical, genetic, and histopathologic features, with a mean follow-up of 7 years. Fifteen females with a DMD mutation (age range 5 to 18 years) were included. Seven patients (46%) presented with clinically evident symptoms and signs such as limb girdle weakness, abnormal gait, and exercise intolerance. The other eight patients (53%) were evaluated because of an incidental finding of elevated level of creatine kinase. Creatine kinase level was elevated in all, ranging from 392 to 13,000 U/L. Calf hypertrophy was observed in eight patients (53%). No patient developed respiratory or cardiac involvement. The most frequent complication was scoliosis (46%). Four patients (29%) also presented minor learning disabilities or behavioral problems. We performed electromyography in half of patients, showing myopathic pattern in four (53%). Muscle biopsy revealed a mosaic reduction of dystrophin in nine available cases. DMD gene mutations were mostly deletions (71%), resulting in loss of reading frame in five patients (36%). The three patients who experienced the most severe disease course were affected either by a nonsense or frameshift mutation. Our analysis suggests that DMD gene mutations may be suspected in a female child with persistently elevated levels of creatine kinase. Evidence of scoliosis, calf hypertrophy, or myopathic pattern at electromyography may also be helpful, and muscle biopsy is always indicative. DMD carriers should be followed for subtle orthopedic and psychiatric complications during childhood. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Whole-body vibration training in children with Duchenne muscular dystrophy and spinal muscular atrophy.

    PubMed

    Vry, Julia; Schubert, Isabel J; Semler, Oliver; Haug, Verena; Schönau, Eckhard; Kirschner, Janbernd

    2014-03-01

    Whole-body-vibration training is used to improve muscle strength and function and might therefore constitute a potential supportive therapy for neuromuscular diseases. To evaluate safety of whole-body vibration training in ambulatory children with Duchenne muscular dystrophy (DMD) and spinal muscular atrophy (SMA). 14 children with DMD and 8 with SMA underwent an 8-week vibration training programme on a Galileo MedM at home (3 × 3 min twice a day, 5 days a week). Primary outcome was safety of the training, assessed clinically and by measuring serum creatine kinase levels. Secondary outcome was efficacy as measured by changes in time function tests, muscle strength and angular degree of dorsiflexion of the ankles. All children showed good clinical tolerance. In boys with DMD, creatine kinase increased by 56% after the first day of training and returned to baseline after 8 weeks of continuous whole-body vibration training. No changes in laboratory parameters were observed in children with SMA. Secondary outcomes showed mild, but not significant, improvements with the exception of the distance walked in the 6-min walking test in children with SMA, which rose from 371.3 m to 402.8 m (p < 0.01). Whole-body vibration training is clinically well tolerated in children with DMD and SMA. The relevance of the temporary increase in creatine kinase in DMD during the first days of training is unclear, but it is not related to clinical symptoms or deterioration. Copyright © 2013 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  7. Abnormal branching and regression of the notochord and its relationship to foregut abnormalities.

    PubMed

    Vleesch Dubois, V N; Quan Qi, B; Beasley, S W; Williams, A

    2002-04-01

    An abnormally positioned notochord has been reported in embryos that develop foregut abnormalities, vertebral defects and other abnormalities of the VATER association. This study examines the patterns of regression of the abnormal notochord in the rat model of the VATER association and investigates the relationship between developmental abnormalities of the notochord and those of the vertebra and foregut. Timed-pregnant Sprague-Dawley rats were given daily intraperitoneal injections of 1.75 mg/kg adriamycin on gestational days 6 - 9 inclusive. Rats were sacrificed between days 14 and 20 and their embryos harvested, histologically sectioned and stained and examined serially. The location and appearance of the degenerating notochord and its relationship to regional structural defects were analysed. All 26 embryos exposed to adriamycin developed foregut abnormalities and had an abnormal notochord. The notochord disappeared by a process of apoptotic degeneration that lagged behind that of the normal embryo: the notochord persisted in the abnormal embryo beyond day 17, whereas in the normal rat it had already disappeared. Similarly, formation of the nucleus pulposus was delayed. Vertebral abnormalities occurred when the notochord was ventrally-positioned. The notochord disappears during day 16 in the normal embryo whereas abnormal branches of the notochord persist until day 19 in the adriamycin-treated embryo. Degeneration of the notochord is dominated by apoptosis. An excessively ventrally-placed notochord is closely associated with abnormalities of the vertebral column, especially hemivertebrae.

  8. Swallow Characteristics in Patients with Oculopharyngeal Muscular Dystrophy

    ERIC Educational Resources Information Center

    Palmer, Phyllis M.; Neel, Amy T.; Sprouls, Gwyneth; Morrison, Leslie

    2010-01-01

    Purpose: This prospective investigation evaluates oral weakness and its impact on swallow function, weight, and quality of life in patients with oculopharyngeal muscular dystrophy (OPMD). Method: Intraoral pressure, swallow pressure, and endurance were measured using an Iowa Oral Performance Instrument in participants with OPMD and matched…

  9. Genetic modifiers of muscular dystrophy act on sarcolemmal resealing and recovery from injury

    PubMed Central

    Quattrocelli, Mattia; Capote, Joanna; Ohiri, Joyce C.; Warner, James L.; Vo, Andy H.; Hadhazy, Michele; Demonbreun, Alexis R.; Spencer, Melissa J.; McNally, Elizabeth M.

    2017-01-01

    Genetic disruption of the dystrophin complex produces muscular dystrophy characterized by a fragile muscle plasma membrane leading to excessive muscle degeneration. Two genetic modifiers of Duchenne Muscular Dystrophy implicate the transforming growth factor β (TGFβ) pathway, osteopontin encoded by the SPP1 gene and latent TGFβ binding protein 4 (LTBP4). We now evaluated the functional effect of these modifiers in the context of muscle injury and repair to elucidate their mechanisms of action. We found that excess osteopontin exacerbated sarcolemmal injury, and correspondingly, that loss of osteopontin reduced injury extent both in isolated myofibers and in muscle in vivo. We found that ablation of osteopontin was associated with reduced expression of TGFβ and TGFβ-associated pathways. We identified that increased TGFβ resulted in reduced expression of Anxa1 and Anxa6, genes encoding key components of the muscle sarcolemma resealing process. Genetic manipulation of Ltbp4 in dystrophic muscle also directly modulated sarcolemmal resealing, and Ltbp4 alleles acted in concert with Anxa6, a distinct modifier of muscular dystrophy. These data provide a model in which a feed forward loop of TGFβ and osteopontin directly impacts the capacity of muscle to recover from injury, and identifies an intersection of genetic modifiers on muscular dystrophy. PMID:29065150

  10. Genetic modifiers of muscular dystrophy act on sarcolemmal resealing and recovery from injury.

    PubMed

    Quattrocelli, Mattia; Capote, Joanna; Ohiri, Joyce C; Warner, James L; Vo, Andy H; Earley, Judy U; Hadhazy, Michele; Demonbreun, Alexis R; Spencer, Melissa J; McNally, Elizabeth M

    2017-10-01

    Genetic disruption of the dystrophin complex produces muscular dystrophy characterized by a fragile muscle plasma membrane leading to excessive muscle degeneration. Two genetic modifiers of Duchenne Muscular Dystrophy implicate the transforming growth factor β (TGFβ) pathway, osteopontin encoded by the SPP1 gene and latent TGFβ binding protein 4 (LTBP4). We now evaluated the functional effect of these modifiers in the context of muscle injury and repair to elucidate their mechanisms of action. We found that excess osteopontin exacerbated sarcolemmal injury, and correspondingly, that loss of osteopontin reduced injury extent both in isolated myofibers and in muscle in vivo. We found that ablation of osteopontin was associated with reduced expression of TGFβ and TGFβ-associated pathways. We identified that increased TGFβ resulted in reduced expression of Anxa1 and Anxa6, genes encoding key components of the muscle sarcolemma resealing process. Genetic manipulation of Ltbp4 in dystrophic muscle also directly modulated sarcolemmal resealing, and Ltbp4 alleles acted in concert with Anxa6, a distinct modifier of muscular dystrophy. These data provide a model in which a feed forward loop of TGFβ and osteopontin directly impacts the capacity of muscle to recover from injury, and identifies an intersection of genetic modifiers on muscular dystrophy.

  11. Muscular and Cardiorespiratory Fitness in Homeschool versus Public School Children.

    PubMed

    Kabiri, Laura S; Mitchell, Katy; Brewer, Wayne; Ortiz, Alexis

    2017-08-01

    The growth and unregulated structure of homeschooling creates an unknown population in regard to muscular and cardiorespiratory fitness. The purpose of this research was to compare muscular and cardiorespiratory fitness between elementary school aged homeschool and public school children. Homeschool children ages 8-11 years old (n = 75) completed the curl-up, 90° push-up, and Progressive Aerobic Capacity Endurance Run (PACER) portions of the FitnessGram to assess abdominal and upper body strength and endurance as well as cardiorespiratory fitness. Comparisons to public school children (n = 75) were made using t tests and chi-square tests. Homeschool children showed significantly lower abdominal (t(148) = -11.441, p < .001; χ 2 (1) = 35.503, p < .001) and upper body (t(148) = -3.610, p < .001; χ 2 (1) = 4.881, p = .027) strength and endurance. There were no significant differences in cardiorespiratory fitness by total PACER laps (t(108) = 0.879, p = .381) or estimated VO 2max (t(70) = 1.187, p = .239; χ 2 (1) = 1.444, p = .486). Homeschool children showed significantly lower levels of both abdominal and upper body muscular fitness compared with their age and gender matched public school peers but no difference in cardiorespiratory fitness.

  12. Rapidly progressive heart failure requiring transplantation in muscular dystrophy: a need for frequent screening.

    PubMed

    Pick, Justin M; Ellis, Zachary D; Alejos, Juan C; Chang, Anthony C

    2017-11-01

    Fukuyama congenital muscular dystrophy weakens both skeletal and cardiac muscles, but the rate of cardiomyopathic progression can accelerate faster than that of skeletal muscles. A 14-year-old boy with Fukuyama congenital muscular dystrophy presented with mild skeletal myopathy but severe cardiomyopathy requiring heart transplantation within 1 year of declining heart function. These patients need frequent screening regardless of musculoskeletal symptoms.

  13. A Cross-Sectional Study of School Experiences of Boys with Duchenne and Becker Muscular Dystrophy

    ERIC Educational Resources Information Center

    Soim, Aida; Lamb, Molly; Campbell, Kimberly; Pandya, Shree; Peay, Holly; Howard, James F., Jr.; Fox, Deborah

    2016-01-01

    The objectives of this study were to investigate types of supportive school services received and factors related to provision of these services. We conducted a cross-sectional study to describe the school experience of males with Duchenne and Becker muscular dystrophies. Study subjects were identified through the Muscular Dystrophy Surveillance,…

  14. Limb-girdle muscular dystrophy and Miyoshi myopathy in an aboriginal Canadian kindred map to LGMD2B and segregate with the same haplotype

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Weiler, T.; Nylen, E.; Wrogemann, K.

    1996-10-01

    We report the results of our investigations of a large, inbred, aboriginal Canadian kindred with nine muscular dystrophy patients. The ancestry of all but two of the carrier parents could be traced to a founder couple, seven generations back. Seven patients presented with proximal myopathy consistent with limb girdle-type muscular dystrophy (LGMD), whereas two patients manifested predominantly distal wasting and weakness consistent with Miyoshi myopathy (distal autosomal recessive muscular dystrophy) (MM). Age at onset of symptoms, degree of creatine kinase elevation, and muscle histology were similar in both phenotypes. Segregation of LGMD/MM is consistent with autosomal recessive inheritance, and themore » putative locus is significantly linked (LOD scores >3.0) to six marker loci that span the region of the LGMD2B locus on chromosome 2p. Our initial hypothesis that the affected patients would all be homozygous by descent for microsatellite markers surrounding the disease locus was rejected. Rather, two different core haplotypes, encompassing a 4-cM region spanned by D2S291-D2S145-D2S286, segregated with the disease, indicating that there are two mutant alleles of independent origin in this kindred. There was no association, however, between the two different haplotypes and clinical variability; they do not distinguish between the LGMD and MM phenotypes. Thus, we conclude that LGMD and MM in our population are caused by the same mutation in LGMD2B and that additional factors, both genetic and nongenetic, must contribute to the clinical phenotype. 37 refs., 2 figs., 2 tabs.« less

  15. Abnormalities in Osteoclastogenesis and Decreased Tumorigenesis in Mice Deficient for Ovarian Cancer G Protein-Coupled Receptor 1

    PubMed Central

    Li, Hui; Wang, Dongmei; Singh, Lisam Shanjukumar; Berk, Michael; Tan, Haiyan; Zhao, Zhenwen; Steinmetz, Rosemary; Kirmani, Kashif; Wei, Gang; Xu, Yan

    2009-01-01

    Ovarian cancer G protein-coupled receptor 1 (OGR1) has been shown to be a proton sensing receptor in vitro. We have shown that OGR1 functions as a tumor metastasis suppressor gene when it is over-expressed in human prostate cancer cells in vivo. To examine the physiological functions of OGR1, we generated conditional OGR1 deficient mice by homologous recombination. OGR1 deficient mice were viable and upon gross-inspection appeared normal. Consistent with in vitro studies showing that OGR1 is involved in osteoclastogenesis, reduced osteoclasts were detected in OGR1 deficient mice. A pH-dependent osteoclasts survival effect was also observed. However, overall abnormality in the bones of these animals was not observed. In addition, melanoma cell tumorigenesis was significantly inhibited in OGR1 deficient mice. OGR1 deficient mice in the mixed background produced significantly less peritoneal macrophages when stimulated with thioglycolate. These macrophages also showed altered extracellular signal-regulated kinases (ERK) activation and nitric oxide (NO) production in response to lipopolysaccharide. OGR1-dependent pH responses assessed by cAMP production and cell survival in macrophages or brown fat cells were not observed, presumably due to the presence of other proton sensing receptors in these cells. Our results indicate that OGR1's role in osteoclastogenesis is not strong enough to affect overall bone development and its role in tumorigenesis warrants further investigation. The mice generated can be potentially used for several disease models, including cancers or osteoclast-related diseases. PMID:19479052

  16. Muscle Weakness and Speech in Oculopharyngeal Muscular Dystrophy

    ERIC Educational Resources Information Center

    Neel, Amy T.; Palmer, Phyllis M.; Sprouls, Gwyneth; Morrison, Leslie

    2015-01-01

    Purpose: We documented speech and voice characteristics associated with oculopharyngeal muscular dystrophy (OPMD). Although it is a rare disease, OPMD offers the opportunity to study the impact of myopathic weakness on speech production in the absence of neurologic deficits in a relatively homogeneous group of speakers. Methods: Twelve individuals…

  17. Vascular anatomy of the medial sural artery perforator flap: a new classification system of intra-muscular branching patterns.

    PubMed

    Dusseldorp, Joseph R; Pham, Quy J; Ngo, Quan; Gianoutsos, Mark; Moradi, Pouria

    2014-09-01

    The medial sural artery perforator (MSAP) flap is a versatile fasciocutaneous flap. The main difficulty encountered when raising the MSAP flap is in obtaining adequate pedicle length during intra-muscular dissection. The objective of this study was to determine the pattern of intra-muscular course of the MSAP flap pedicle. 14 cadaveric specimens were dissected and CT angiograms of 84 legs were examined. The intra-muscular branching pattern and depths of the medial sural artery branches were analyzed. The number of perforators, position of the dominant perforator and both intra-muscular and total pedicle length were also recorded and compared to existing anatomical data. Three types of arterial branching pattern were identified within the medial gastrocnemius, demonstrating one (31%), two (59%) or three or more (10%) main branches. A dominant perforator from the medial sural artery was present in 92% of anatomical specimens (13/14). Vertically, the location of the perforator from the popliteal crease was on average 13 cm (±2 cm). Transversely, the perforator originated 2.5 cm (±1 cm) from the posterior midline. Using CT angiography it was possible in 10 consecutive patients to identify a more superficial intra-muscular branch and determine the leg with the optimal branching pattern type for flap harvest. This study is the first to describe the variability of the intra-muscular arterial anatomy of the medial head of gastrocnemius muscle. Surgeons utilizing the MSAP flap option should be aware of the possible branching pattern types and consequently the differing perforator distribution and depths of intra-muscular branches. Routine use of pre-operative CT angiogram may help determine which leg has the most favorable branching pattern type and intra-muscular course for flap harvest. Copyright © 2014 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

  18. Sarcospan Regulates Cardiac Isoproterenol Response and Prevents Duchenne Muscular Dystrophy-Associated Cardiomyopathy.

    PubMed

    Parvatiyar, Michelle S; Marshall, Jamie L; Nguyen, Reginald T; Jordan, Maria C; Richardson, Vanitra A; Roos, Kenneth P; Crosbie-Watson, Rachelle H

    2015-12-23

    Duchenne muscular dystrophy is a fatal cardiac and skeletal muscle disease resulting from mutations in the dystrophin gene. We have previously demonstrated that a dystrophin-associated protein, sarcospan (SSPN), ameliorated Duchenne muscular dystrophy skeletal muscle degeneration by activating compensatory pathways that regulate muscle cell adhesion (laminin-binding) to the extracellular matrix. Conversely, loss of SSPN destabilized skeletal muscle adhesion, hampered muscle regeneration, and reduced force properties. Given the importance of SSPN to skeletal muscle, we investigated the consequences of SSPN ablation in cardiac muscle and determined whether overexpression of SSPN into mdx mice ameliorates cardiac disease symptoms associated with Duchenne muscular dystrophy cardiomyopathy. SSPN-null mice exhibited cardiac enlargement, exacerbated cardiomyocyte hypertrophy, and increased fibrosis in response to β-adrenergic challenge (isoproterenol; 0.8 mg/day per 2 weeks). Biochemical analysis of SSPN-null cardiac muscle revealed reduced sarcolemma localization of many proteins with a known role in cardiomyopathy pathogenesis: dystrophin, the sarcoglycans (α-, δ-, and γ-subunits), and β1D integrin. Transgenic overexpression of SSPN in Duchenne muscular dystrophy mice (mdx(TG)) improved cardiomyofiber cell adhesion, sarcolemma integrity, cardiac functional parameters, as well as increased expression of compensatory transmembrane proteins that mediate attachment to the extracellular matrix. SSPN regulates sarcolemmal expression of laminin-binding complexes that are critical to cardiac muscle function and protects against transient and chronic injury, including inherited cardiomyopathy. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  19. Mild and severe muscular dystrophy caused by a single {gamma}-sarcoglycan mutation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    McNally, E.M.; Boennemann, C.G.; Lidov, H.G.W.

    1996-11-01

    Autosomal recessive muscular dystrophy is genetically heterogeneous. One form of this disorder, limb-girdle muscular dystrophy type 2C (LGMD 2C), is prevalent in northern Africa and has been shown to be associated with a single mutation in the gene encoding the dystrophin-associated protein {gamma}-sarcoglycan. The previous mutation analysis of {gamma}-sarcoglycan required the availability of muscle biopsies. To establish a mutation assay for genomic DNA, the intron-exon structure of the {gamma}-sarcoglycan gene was determined, and primers were designed to amplify each of the exons encoding {gamma}-sarcoglycan. We studied a group of Brazilian muscular dystrophy patients for mutations in the {gamma}-sarcoglycan gene. Thesemore » patients were selected on the basis of autosomal inheritance and/or the presence of normal dystrophin and/or deficiency of {alpha}-sarcoglycan immunostaining. Four of 19 patients surveyed had a single, homozygous mutation in the {gamma}-sarcoglycan gene. The mutation identified in these patients, all of African-Brazilian descent, is identical to that seen in the North African population, suggesting that even patients of remote African descent may carry this mutation. The phenotype in these patients varied considerably. Of four families with an identical mutation, three have a severe Duchenne-like muscular dystrophy. However, one family has much milder symptoms, suggesting that other loci may be present that modify the severity of the clinical course resulting from {gamma}-sarcoglycan gene mutations. 19 refs., 5 figs., 3 tabs.« less

  20. Computational modeling of muscular thin films for cardiac repair

    NASA Astrophysics Data System (ADS)

    Böl, Markus; Reese, Stefanie; Parker, Kevin Kit; Kuhl, Ellen

    2009-03-01

    Motivated by recent success in growing biohybrid material from engineered tissues on synthetic polymer films, we derive a computational simulation tool for muscular thin films in cardiac repair. In this model, the polydimethylsiloxane base layer is simulated in terms of microscopically motivated tetrahedral elements. Their behavior is characterized through a volumetric contribution and a chain contribution that explicitly accounts for the polymeric microstructure of networks of long chain molecules. Neonatal rat ventricular cardiomyocytes cultured on these polymeric films are modeled with actively contracting truss elements located on top of the sheet. The force stretch response of these trusses is motivated by the cardiomyocyte force generated during active contraction as suggested by the filament sliding theory. In contrast to existing phenomenological models, all material parameters of this novel model have a clear biophyisical interpretation. The predictive features of the model will be demonstrated through the simulation of muscular thin films. First, the set of parameters will be fitted for one particular experiment documented in the literature. This parameter set is then used to validate the model for various different experiments. Last, we give an outlook of how the proposed simulation tool could be used to virtually predict the response of multi-layered muscular thin films. These three-dimensional constructs show a tremendous regenerative potential in repair of damaged cardiac tissue. The ability to understand, tune and optimize their structural response is thus of great interest in cardiovascular tissue engineering.

  1. Overexpression of Latent TGFβ Binding Protein 4 in Muscle Ameliorates Muscular Dystrophy through Myostatin and TGFβ

    PubMed Central

    Gardner, Brandon B.; Gao, Quan Q.; Hadhazy, Michele; Vo, Andy H.; Wren, Lisa; Molkentin, Jeffery D.; McNally, Elizabeth M.

    2016-01-01

    Latent TGFβ binding proteins (LTBPs) regulate the extracellular availability of latent TGFβ. LTBP4 was identified as a genetic modifier of muscular dystrophy in mice and humans. An in-frame insertion polymorphism in the murine Ltbp4 gene associates with partial protection against muscular dystrophy. In humans, nonsynonymous single nucleotide polymorphisms in LTBP4 associate with prolonged ambulation in Duchenne muscular dystrophy. To better understand LTBP4 and its role in modifying muscular dystrophy, we created transgenic mice overexpressing the protective murine allele of LTBP4 specifically in mature myofibers using the human skeletal actin promoter. Overexpression of LTBP4 protein was associated with increased muscle mass and proportionally increased strength compared to age-matched controls. In order to assess the effects of LTBP4 in muscular dystrophy, LTBP4 overexpressing mice were bred to mdx mice, a model of Duchenne muscular dystrophy. In this model, increased LTBP4 led to greater muscle mass with proportionally increased strength, and decreased fibrosis. The increase in muscle mass and reduction in fibrosis were similar to what occurs when myostatin, a related TGFβ family member and negative regulator of muscle mass, was deleted in mdx mice. Supporting this, we found that myostatin forms a complex with LTBP4 and that overexpression of LTBP4 led to a decrease in myostatin levels. LTBP4 also interacted with TGFβ and GDF11, a protein highly related to myostatin. These data identify LTBP4 as a multi-TGFβ family ligand binding protein with the capacity to modify muscle disease through overexpression. PMID:27148972

  2. Overexpression of Latent TGFβ Binding Protein 4 in Muscle Ameliorates Muscular Dystrophy through Myostatin and TGFβ.

    PubMed

    Lamar, Kay-Marie; Bogdanovich, Sasha; Gardner, Brandon B; Gao, Quan Q; Miller, Tamari; Earley, Judy U; Hadhazy, Michele; Vo, Andy H; Wren, Lisa; Molkentin, Jeffery D; McNally, Elizabeth M

    2016-05-01

    Latent TGFβ binding proteins (LTBPs) regulate the extracellular availability of latent TGFβ. LTBP4 was identified as a genetic modifier of muscular dystrophy in mice and humans. An in-frame insertion polymorphism in the murine Ltbp4 gene associates with partial protection against muscular dystrophy. In humans, nonsynonymous single nucleotide polymorphisms in LTBP4 associate with prolonged ambulation in Duchenne muscular dystrophy. To better understand LTBP4 and its role in modifying muscular dystrophy, we created transgenic mice overexpressing the protective murine allele of LTBP4 specifically in mature myofibers using the human skeletal actin promoter. Overexpression of LTBP4 protein was associated with increased muscle mass and proportionally increased strength compared to age-matched controls. In order to assess the effects of LTBP4 in muscular dystrophy, LTBP4 overexpressing mice were bred to mdx mice, a model of Duchenne muscular dystrophy. In this model, increased LTBP4 led to greater muscle mass with proportionally increased strength, and decreased fibrosis. The increase in muscle mass and reduction in fibrosis were similar to what occurs when myostatin, a related TGFβ family member and negative regulator of muscle mass, was deleted in mdx mice. Supporting this, we found that myostatin forms a complex with LTBP4 and that overexpression of LTBP4 led to a decrease in myostatin levels. LTBP4 also interacted with TGFβ and GDF11, a protein highly related to myostatin. These data identify LTBP4 as a multi-TGFβ family ligand binding protein with the capacity to modify muscle disease through overexpression.

  3. Evidence for linkage disequilibrium in chromosome 13-linked Duchenne-like muscular dystrophy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Othmane, K.B.; Speer, M.C.; Stauffer, J.

    1995-09-01

    Duchenne-like muscular dystrophy (DLMD) is an autosomal recessive Limb Girdle muscular dystrophy (LGMD2C) characterized by late age of onset, proximal muscle weakness leading to disability, high creatine kinase values, normal intelligence and normal dystrophin in muscle biopsy. We have shown previously that three DLMD families from Tunisia are linked to chromosome 13q12. To further localize the LGMD2C gene, we have investigated seven additional families (119 individuals). Both genotyping and two-point linkage analysis were performed as described elsewhere. 7 refs., 1 fig., 1 tab.

  4. Regulatory T cells suppress muscle inflammation and injury in muscular dystrophy.

    PubMed

    Villalta, S Armando; Rosenthal, Wendy; Martinez, Leonel; Kaur, Amanjot; Sparwasser, Tim; Tidball, James G; Margeta, Marta; Spencer, Melissa J; Bluestone, Jeffrey A

    2014-10-15

    We examined the hypothesis that regulatory T cells (Tregs) modulate muscle injury and inflammation in the mdx mouse model of Duchenne muscular dystrophy (DMD). Although Tregs were largely absent in the muscle of wild-type mice and normal human muscle, they were present in necrotic lesions, displayed an activated phenotype, and showed increased expression of interleukin-10 (IL-10) in dystrophic muscle from mdx mice. Depletion of Tregs exacerbated muscle injury and the severity of muscle inflammation, which was characterized by an enhanced interferon-γ (IFN-γ) response and activation of M1 macrophages. To test the therapeutic value of targeting Tregs in muscular dystrophy, we treated mdx mice with IL-2/anti-IL-2 complexes and found that Tregs and IL-10 concentrations were increased in muscle, resulting in reduced expression of cyclooxygenase-2 and decreased myofiber injury. These findings suggest that Tregs modulate the progression of muscular dystrophy by suppressing type 1 inflammation in muscle associated with muscle fiber injury, and highlight the potential of Treg-modulating agents as therapeutics for DMD. Copyright © 2014, American Association for the Advancement of Science.

  5. Genetics Home Reference: Duchenne and Becker muscular dystrophy

    MedlinePlus

    ... Citation on PubMed Mah JK, Korngut L, Dykeman J, Day L, Pringsheim T, Jette N. A systematic review and meta-analysis on the epidemiology of Duchenne and Becker muscular dystrophy. Neuromuscul Disord. 2014 Jun;24(6):482-91. doi: 10.1016/j.nmd.2014.03.008. Epub 2014 Mar 22. ...

  6. Influence of bench angle on upper extremity muscular activation during bench press exercise.

    PubMed

    Lauver, Jakob D; Cayot, Trent E; Scheuermann, Barry W

    2016-01-01

    This study compared the muscular activation of the pectoralis major, anterior deltoid and triceps brachii during a free-weight barbell bench press performed at 0°, 30°, 45° and -15° bench angles. Fourteen healthy resistance trained males (age 21.4 ± 0.4 years) participated in this study. One set of six repetitions for each bench press conditions at 65% one repetition maximum were performed. Surface electromyography (sEMG) was utilised to examine the muscular activation of the selected muscles during the eccentric and concentric phases. In addition, each phase was subdivided into 25% contraction durations, resulting in four separate time points for comparison between bench conditions. The sEMG of upper pectoralis displayed no difference during any of the bench conditions when examining the complete concentric contraction, however differences during 26-50% contraction duration were found for both the 30° [122.5 ± 10.1% maximal voluntary isometric contraction (MVIC)] and 45° (124 ± 9.1% MVIC) bench condition, resulting in greater sEMG compared to horizontal (98.2 ± 5.4% MVIC) and -15 (96.1 ± 5.5% MVIC). The sEMG of lower pectoralis was greater during -15° (100.4 ± 5.7% MVIC), 30° (86.6 ± 4.8% MVIC) and horizontal (100.1 ± 5.2% MVIC) bench conditions compared to the 45° (71.9 ± 4.5% MVIC) for the whole concentric contraction. The results of this study support the use of a horizontal bench to achieve muscular activation of both the upper and lower heads of the pectoralis. However, a bench incline angle of 30° or 45° resulted in greater muscular activation during certain time points, suggesting that it is important to consider how muscular activation is affected at various time points when selecting bench press exercises.

  7. Proximal spinal muscular atrophy: current orthopedic perspective

    PubMed Central

    Haaker, Gerrit; Fujak, Albert

    2013-01-01

    Spinal muscular atrophy (SMA) is a hereditary neuromuscular disease of lower motor neurons that is caused by a defective “survival motor neuron” (SMN) protein that is mainly associated with proximal progressive muscle weakness and atrophy. Although SMA involves a wide range of disease severity and a high mortality and morbidity rate, recent advances in multidisciplinary supportive care have enhanced quality of life and life expectancy. Active research for possible treatment options has become possible since the disease-causing gene defect was identified in 1995. Nevertheless, a causal therapy is not available at present, and therapeutic management of SMA remains challenging; the prolonged survival is increasing, especially orthopedic, respiratory and nutritive problems. This review focuses on orthopedic management of the disease, with discussion of key aspects that include scoliosis, muscular contractures, hip joint disorders, fractures, technical devices, and a comparative approach of conservative and surgical treatment. Also emphasized are associated complications including respiratory involvement, perioperative care and anesthesia, nutrition problems, and rehabilitation. The SMA disease course can be greatly improved with adequate therapy with established orthopedic procedures in a multidisciplinary therapeutic approach. PMID:24399883

  8. The relationship between the drive for muscularity and muscle dysmorphia in male and female weight trainers.

    PubMed

    Robert, Courtney A; Munroe-Chandler, Krista J; Gammage, Kimberley L

    2009-09-01

    Muscle dysmorphia is a form of body dysmorphic disorder in which individuals have a pathological preoccupation with their muscularity and, more specifically, an extreme fear that their bodies are too small. Relatively few empirical studies have been completed on muscle dysmorphia, and even fewer studies on the relationship between the drive for muscularity and muscle dysmorphia in men and women. The purpose of this research was to examine the relationship between the drive for muscularity and muscle dysmorphia in male (n = 55) and female (n = 59) recreational weight trainers. Results revealed that the behavior and diet subscales of the drive for muscularity significantly predicted muscle dysmorphia in males and females accounting for 69% and 46% of the total variance, respectively. Although the overall scores of muscle dysmorphia do not indicate clinical levels, these findings suggest that behaviors such as arranging one's schedule around his/her training regimen and dieting in order to gain muscle predict characteristics of muscle dysmorphia in men and women.

  9. Spinal Muscular Atrophy Type I: Is It Ethical to Standardize Supportive Care Intervention in Clinical Trials?

    PubMed

    Finkel, Richard S; Bishop, Kathie M; Nelson, Robert M

    2017-02-01

    The natural history of spinal muscular atrophy type I (SMA-I) has changed as improved medical support has become available. With investigational drugs for spinal muscular atrophy now in clinical trials, efficient trial design focuses on enrolling recently diagnosed infants, providing best available supportive care, and minimizing subject variation. The quandary has arisen whether it is ethically appropriate to specify a predefined level of nutritional and/or ventilation support for spinal muscular atrophy type I subjects while participating in these studies. We conducted a survey at 2 spinal muscular atrophy investigator meetings involving physician investigators, clinical evaluators, and study coordinators from North America, Europe, and Asia-Pacific. Each group endorsed the concept that having a predefined degree of nutritional and ventilation support was warranted in this context. We discuss how autonomy, beneficence/non-maleficence, noncoercion, social benefit, and equipoise can be maintained when a predefined level of supportive care is proposed, for participation in a clinical trial.

  10. Validation of the Spanish version of the Drive for Muscularity Scale (DMS) among males: Confirmatory factor analysis.

    PubMed

    Sepulveda, Ana R; Parks, Melissa; de Pellegrin, Yolanda; Anastasiadou, Dimitra; Blanco, Miriam

    2016-04-01

    Drive for Muscularity (DM) has been shown to be a relevant construct for measuring and understanding male body image. For this reason, it is important to have reliable and valid instruments with which to measure DM, and to date no such instruments exist in Spain. This study analyzes the psychometric and structural properties of the Drive for Muscularity Scale (DMS) in a sample of Spanish adolescent males (N=212), with the aim of studying the structural validity of the scale by using a confirmatory factor analysis (CFA), as well as analyzing the internal consistency and construct (convergent and discriminant) and concurrent validity of the instrument. After testing three models, results indicated that the best structure was a two-dimensional model, with the factors of muscularity-oriented body image (MBI) and muscularity behavior (MB). The scale showed good internal consistency (α=.90) and adequate construct validity. Furthermore, significant associations were found between DM and increased difficulties in emotional regulation (rho=.37) and low self-esteem (rho=-.19). Findings suggest that the two-factor structure may be used when assessing drive for muscularity among adolescent males in Spain. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Abnormal Uterine Bleeding FAQ

    MedlinePlus

    ... Abnormal Uterine Bleeding • What is a normal menstrual cycle? • When is bleeding abnormal? • At what ages is ... abnormal bleeding? •Glossary What is a normal menstrual cycle? The normal length of the menstrual cycle is ...

  12. Neural Issues in the Control of Muscular Strength

    ERIC Educational Resources Information Center

    Kamen, Gary

    2004-01-01

    During the earliest stages of resistance exercise training, initial muscular strength gains occur too rapidly to be explained solely by muscle-based mechanisms. However, increases in surface-based EMG amplitude as well as motor unit discharge rate provide some insight to the existence of neural mechanisms in the earliest phases of resistance…

  13. Parental decisions to abort or continue a pregnancy following prenatal diagnosis of chromosomal abnormalities in a setting where termination of pregnancy is not legally available.

    PubMed

    Quadrelli, Roberto; Quadrelli, Andrea; Mechoso, Búrix; Laufer, Mauricio; Jaumandreu, Ciro; Vaglio, Alicia

    2007-03-01

    To learn about parental decisions to abort or continue a pregnancy after prenatal diagnosis of chromosomal abnormalities among the population in Uruguay. Between 1982 and 2003, 14 656 amniocentesis and 2740 chorionic villus samplings were performed in a referral Genetic Unit. Chromosomal anomalies were found in 376 cases (2.16%) and included Down syndrome, aneuploidies in which a severe prognosis was expected, sex chromosome aneuploidy and aneuploidies with a low risk of an abnormal clinical phenotype. The couples that received abnormal results were contacted by phone and asked if they had continued or interrupted the pregnancy after the diagnosis and genetic counseling. We contacted 207 couples (55%). When confronted with Down syndrome or an aneuploidy in which a severe prognosis was expected, 89% and 96% of patients, respectively, decided to terminate the pregnancy. When confronted with sex chromosome aneuploidy or aneuploidies with a low risk of an abnormal clinical phenotype, 79% and 90% of patients, respectively, decided to continue the pregnancy. The present study shows that when faced with an anomaly such as Down syndrome and aneuploidies in which a severe prognosis was expected, most of the couples decided to terminate the pregnancy, although TOP is not legally available in Uruguay. Copyright (c) 2007 John Wiley & Sons, Ltd.

  14. Trace elements in seminal plasma of men from infertile couples.

    PubMed

    Guzikowski, Wojciech; Szynkowska, Małgorzata I; Motak-Pochrzęst, Hanna; Pawlaczyk, Aleksandra; Sypniewski, Stanisław

    2015-06-19

    An analysis of lead, zinc, cadmium and other trace elements in semen of men from infertile couples was performed to determine the association between abnormal semen parameters and enviromental or occupational exposure to some trace metals. Presence of manganese, cobalt, nickel, copper, zinc, molybdenum, cadmium, tin and lead was measured in seminal plasma of 34 men from infertile couples using spectrometry with time-of-flight analysis. Correlations among sperm parameters and trace metals were determined using cluster analysis and Pearson's correlation coefficient. Abnormally high concentrations of lead, cadmium, zinc and cobalt were found in 23 seminal plasma of men from infertile couples. The most consistent evidence was determined for an association between high cadmium concentration in seminal plasma and sperm count, motility and morphology below reference limits (p < 0.01). A correlation of significantly increased tin level and reduced sperm count in semen of men with limited fertility potential was observed (p = 0.04). In our study we observed a correlation of tin level with sperm count in semen of men with limited fertility potential.

  15. [Propofol anesthesia for a patient with progressive muscular dystrophy].

    PubMed

    Egi, Moritoki; Tokioka, Hiroaki; Chikai, Takashi; Fukushima, Tomihiro; Ishizu, Tomoko; Tanaka, Toshiaki; Kosogabe, Yoshinori

    2002-02-01

    We gave propofol anesthesia to a patient with limb-girdle type of progressive muscular dystrophy. A 42 year-old male was to have skin graft for third degree burn. His respiratory function test showed %VC of 73.6% and %FEV1.0 of 107.6%. Arterial blood gas data were within normal ranges. He was anesthetized with propofol, fentanyl, vecuronium and nitrous oxide. During position change, Wenckebach type of second degree AV block occurred. AV block returned to sinus rhythm easily by injection of ephedrine hydrochloride and atropine sulfate, and reduction of propofol infusion rate. There were no perioperative respiratory complications and no clinical manifestations of malignant hyperthermia. Propofol anesthesia is suitable for limb-girdle type of progressive muscular dystrophy, because of very little possibility of triggering malignant hyperthermia, rapid awaking, minimal residual effects of the respiratory system, and easiness in controlling anesthetic depth.

  16. Effect of the bitterness of food on muscular activity and masticatory movement.

    PubMed

    Okada, Yamato; Shiga, Hiroshi

    2017-10-01

    The purpose of this study was to clarify the effect of the bitterness of food on muscular activity and masticatory movement. Twenty healthy subjects were asked to chew a non-bitter gummy jelly and a bitter gummy jelly on their habitual chewing side. The masseter muscular activity and the movement of mandibular incisal point were recorded simultaneously. For all cycles excluding the first cycle, parameters representing the muscular activity (total integral value and integral value per cycle) and masticatory movement (path, rhythm, and stability) were calculated and compared between the two types of gummy jellies. The total integral value of masseter muscular activity during the chewing of bitter gummy jelly was significantly smaller than during the chewing of non-bitter gummy jelly, however, no definite trends in the integral value per cycle and the stability of movement were observed. The parameters representing the movement path tended to be small during the chewing of bitter gummy jelly than during the chewing of non-bitter gummy jelly. The masticatory width was significantly smaller during the chewing of bitter gummy jelly. The parameters representing the rhythm of movement were significantly longer during the chewing of bitter gummy jelly than during the chewing of non-bitter gummy jelly. From these results it was suggested that the bitterness of food does not affect the integral value per cycle or the stability of the masticatory movement, but it does affect the movement path and rhythm, with narrowing of the path and slowing of the rhythm. Copyright © 2017 Japan Prosthodontic Society. Published by Elsevier Ltd. All rights reserved.

  17. A human in vitro model of Duchenne muscular dystrophy muscle formation and contractility.

    PubMed

    Nesmith, Alexander P; Wagner, Matthew A; Pasqualini, Francesco S; O'Connor, Blakely B; Pincus, Mark J; August, Paul R; Parker, Kevin Kit

    2016-10-10

    Tongue weakness, like all weakness in Duchenne muscular dystrophy (DMD), occurs as a result of contraction-induced muscle damage and deficient muscular repair. Although membrane fragility is known to potentiate injury in DMD, whether muscle stem cells are implicated in deficient muscular repair remains unclear. We hypothesized that DMD myoblasts are less sensitive to cues in the extracellular matrix designed to potentiate structure-function relationships of healthy muscle. To test this hypothesis, we drew inspiration from the tongue and engineered contractile human muscle tissues on thin films. On this platform, DMD myoblasts formed fewer and smaller myotubes and exhibited impaired polarization of the cell nucleus and contractile cytoskeleton when compared with healthy cells. These structural aberrations were reflected in their functional behavior, as engineered tongues from DMD myoblasts failed to achieve the same contractile strength as healthy tongue structures. These data suggest that dystrophic muscle may fail to organize with respect to extracellular cues necessary to potentiate adaptive growth and remodeling. © 2016 Nesmith et al.

  18. Urine - abnormal color

    MedlinePlus

    ... medlineplus.gov/ency/article/003139.htm Urine - abnormal color To use the sharing features on this page, please enable JavaScript. The usual color of urine is straw-yellow. Abnormally colored urine ...

  19. Genetic predisposition scores associate with muscular strength, size, and trainability.

    PubMed

    Thomaes, Tom; Thomis, Martine; Onkelinx, Steven; Goetschalckx, Kaatje; Fagard, Robert; Lambrechts, Diether; Vanhees, Luc

    2013-08-01

    The number of studies trying to identify genetic sequence variation related to muscular phenotypes has increased enormously. The aim of this study was to identify the role of a genetic predisposition score (GPS) based on earlier identified gene variants for different muscular endophenotypes to explain the individual differences in muscular fitness characteristics and the response to training in patients with coronary artery disease. Two hundred and sixty coronary artery disease patients followed a standard ambulatory, 3-month supervised training program for cardiac patients. Maximal knee extension strength (KES) and rectus femoris diameter were measured at baseline and after rehabilitation. Sixty-five single nucleotide polymorphisms (SNP) in 30 genes were selected based on genotype-phenotype association literature. Backward regression analysis revealed subsets of SNP associated with the different phenotypes. GPS were constructed for all sets of SNP by adding up the strength-increasing alleles. General linear models and multiple stepwise regression analysis were used to test the explained variance of the GPS in baseline and strength responses. Receiver operating characteristic curve analyses were performed to discriminate between high- and low-responder status. GPS were significantly associated with the rectus femoris diameter (P < 0.01) and its response (P < 0.0001), the isometric KES (P < 0.05) and its response (P < 0.01), the isokinetic KES at 60° · s (P < 0.05) and 180° · s (P < 0.001) and their responses to training (P < 0.0001), and the isokinetic KES endurance (P < 0.001) and its change after training (P < 0.0001). The GPS was shown as an independent determinant in baseline and response phenotypes with partial explained variance up to 23%. Receiver operating characteristic analysis showed a significant discriminating accuracy of the models, including the GPS for responses to training, with areas under the curve ranging from 0.62 to 0.85. GPS for muscular

  20. Decreased cerebral perfusion in Duchenne muscular dystrophy patients.

    PubMed

    Doorenweerd, Nathalie; Dumas, Eve M; Ghariq, Eidrees; Schmid, Sophie; Straathof, Chiara S M; Roest, Arno A W; Wokke, Beatrijs H; van Zwet, Erik W; Webb, Andrew G; Hendriksen, Jos G M; van Buchem, Mark A; Verschuuren, Jan J G M; Asllani, Iris; Niks, Erik H; van Osch, Matthias J P; Kan, Hermien E

    2017-01-01

    Duchenne muscular dystrophy is caused by dystrophin gene mutations which lead to the absence of the protein dystrophin. A significant proportion of patients suffer from learning and behavioural disabilities, in addition to muscle weakness. We have previously shown that these patients have a smaller total brain and grey matter volume, and altered white matter microstructure compared to healthy controls. Patients with more distal gene mutations, predicted to affect dystrophin isoforms Dp140 and Dp427, showed greater grey matter reduction. Now, we studied if cerebral blood flow in Duchenne muscular dystrophy patients is altered, since cerebral expression of dystrophin also occurs in vascular endothelial cells and astrocytes associated with cerebral vasculature. T1-weighted anatomical and pseudo-continuous arterial spin labeling cerebral blood flow images were obtained from 26 patients and 19 age-matched controls (ages 8-18 years) on a 3 tesla MRI scanner. Group comparisons of cerebral blood flow were made with and without correcting for grey matter volume using partial volume correction. Results showed that patients had a lower cerebral blood flow than controls (40.0 ± 6.4 and 47.8 ± 6.3 mL/100 g/min respectively, p = 0.0002). This reduction was independent of grey matter volume, suggesting that they are two different aspects of the pathophysiology. Cerebral blood flow was lowest in patients lacking Dp140. There was no difference in CBF between ambulant and non-ambulant patients. Only three patients showed a reduced left ventricular ejection fraction. No correlation between cerebral blood flow and age was found. Our results indicate that cerebral perfusion is reduced in Duchenne muscular dystrophy patients independent of the reduced grey matter volume. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Profiles of muscularity in junior Olympic weight lifters.

    PubMed

    Kanehisa, H; Funato, K; Abe, T; Fukunaga, T

    2005-03-01

    This study aimed to investigate the muscularity of strength-trained junior athletes. Muscle thickness (Mt) values at 10 sites (anterior forearm, anterior upper arm, posterior upper arm, chest, abdomen, back, anterior thigh, posterior thigh, anterior lower leg, and posterior lower leg) were determined in junior Olympic weight lifters (OWL, n=7, 15.1+/-0.3 y, mean+/-SD) and non-athletes (CON, n=13, 15.1+/-0.3 y) using a brightness mode ultrasonography. Skeletal age assessed with the Tanner-Whitehouse II method (20 hand-wrist bones) was similar in OWL (16.4+/-0.7 y) and CON (16.3+/-0.6 y). At the 6 sites (anterior forearm, anterior upper arm, posterior upper arm, chest, back and anterior thigh), OWL showed significantly greater Mt values than CON even in terms of Mt relative to body mass(1/3) Mt x BM(-1/3). On the other hand, there were no significant differences between the 2 groups in the Mt ratios of the anterior to posterior site in the upper arm, thigh and lower leg and those of the back to either the chest or abdomen in the trunk. For OWL only, skeletal age was significantly correlated to Mt x BM(-1/3) at the abdomen (r=0.869, p<0.05) and anterior thigh (r=0.883, p<0.05). The findings here indicate that 1) as compared to adolescent non-athletes, junior Olympic weight lifters show a greater muscularity in the upper body and anterior thigh without predominant development in either of anterior and posterior sites within the same body segment, 2) for junior Olympic weight lifters, the muscularity of abdominal and knee extensor muscles is influenced by the biological maturation.

  2. Muscular fatigue in response to different modalities of CrossFit sessions.

    PubMed

    Maté-Muñoz, José Luis; Lougedo, Juan H; Barba, Manuel; García-Fernández, Pablo; Garnacho-Castaño, Manuel V; Domínguez, Raúl

    2017-01-01

    CrossFit is a new strength and conditioning regimen involving short intense daily workouts called workouts of the day (WOD). This study assesses muscular fatigue levels induced by the three modalities of CrossFit WOD; gymnastics (G), metabolic conditioning (M) and weightlifting (W). 34 healthy subjects undertook three WOD (one per week): a G WOD consisting of completing the highest number of sets of 5 pull-ups, 10 push-ups and 15 air squats in 20 min; an M WOD, in which the maximum number of double skipping rope jumps was executed in 8 sets (20 s), resting (10 s) between sets; and finally, a W WOD in which the maximum number of power cleans was executed in 5 min, lifting a load equivalent to 40% of the individual's 1RM. Before and after each WOD, blood lactate concentrations were measured. Also, before, during, and after each WOD, muscular fatigue was assessed in a countermovement jump test (CMJ). Significant reductions were produced in the mechanical variables jump height, average power and maximum velocity in response to G; and in jump height, mean and peak power, maximum velocity and maximum force in response to W (P<0.01). However, in M, significant reductions in mechanical variables were observed between pre- and mid session (after sets 2, 4, 6 and 8), but not between pre- and post session. Muscular fatigue, reflected by reduced CMJ variables, was produced following the G and W sessions, while recovery of this fatigue was observed at the end of M, likely attributable to rest intervals allowing for the recovery of phosphocreatine stores. Our findings also suggest that the high intensity and volume of exercise in G and W WODs could lead to reduced muscular-tendon stiffness causing a loss of jump ability, related here to a longer isometric phase during the CMJ.

  3. The effects of exposure to muscular male models among men: exploring the moderating role of gym use and exercise motivation.

    PubMed

    Halliwell, Emma; Dittmar, Helga; Orsborn, Amber

    2007-09-01

    This study examines the effects of exposure to the muscular male body ideal on body-focused negative affect among male gym users and non-exercisers. As hypothesized, the impact of media exposure depended on men's exercise status. Non-exercisers (n = 58) reported greater body-focused negative affect after exposure to images of muscular male models than after neutral images (no model controls), whereas gym users (n = 58) showed a tendency for less body-focused negative affect after the model images than after the control images. Furthermore, the extent to which gym users were motivated to increase strength and muscularity moderated these exposure effects; men who reported stronger strength and muscularity exercise motivation reported a greater degree of self-enhancement after exposure to the muscular ideal. The findings are interpreted with respect to likely differences in motives for social comparisons.

  4. A study of muscular tissue of animal origin by reflection-spectroscopy methods

    NASA Astrophysics Data System (ADS)

    Plotnikova, L. V.; Nechiporenko, A. P.; Orekhova, S. M.; Plotnikov, P. P.; Ishevskii, A. L.

    2017-06-01

    A comparative analysis of the spectral characteristics of the surface of muscular tissue of animal origin (pork) and its main components has been performed by the methods of diffuse reflection electronic spectroscopy (DRES) and frustrated total internal reflection IR spectroscopy. The experiments have shown that the application of the DRES method makes it possible to detect more pronounced changes in the surface optical characteristics of muscular tissue and obtain electronic spectra containing information about the component composition of its main parts under successive extraction of sarcoplasmic materials, myofibrillar proteins of the actomyosin complex, and stroma mucopolysaccharides.

  5. [Delayed diagnosis of Duchenne muscular dystrophy in Chile].

    PubMed

    de los Angeles Avaria, M; Kleinsteuber, K; Herrera, L; Carvallo, P

    1999-01-01

    Duchenne muscular dystrophy is the most frequent neuromuscular disease in children. To determine the causes of delayed diagnosis of the disease. The clinical records of 61 children diagnosed as Duchenne progressive muscular dystrophy were analyzed. the first symptoms of the disease were noticed at a mean age of 1.5 years. Parents consulted at the mean age of 3 years, but the accurate diagnosis was made at a mean age of 5.7 years. In only 15% of children, the disease was diagnosed in the first four years of age. Less than 20% of children were referred for an adequate study and the rest were managed mainly as flat feet. Duchenne dystrophy is the most common neuromuscular disorder in children, with an incidence of 1 in 3679 male newborns. The lack of recognition of non specific symptoms such as retardation in independent walking and frequent falls as forms of presentation, is probably the most important cause of diagnostic delay. Strong recommendation is made to measure creatinphosphokinase and to study every male child that is not walking independently by the age of 18 months.

  6. Restoring Dystrophin Expression in Duchenne Muscular Dystrophy Muscle

    PubMed Central

    Hoffman, Eric P.; Bronson, Abby; Levin, Arthur A.; Takeda, Shin'ichi; Yokota, Toshifumi; Baudy, Andreas R.; Connor, Edward M.

    2011-01-01

    The identification of the Duchenne muscular dystrophy gene and protein in the late 1980s led to high hopes of rapid translation to molecular therapeutics. These hopes were fueled by early reports of delivering new functional genes to dystrophic muscle in mouse models using gene therapy and stem cell transplantation. However, significant barriers have thwarted translation of these approaches to true therapies, including insufficient therapeutic material (eg, cells and viral vectors), challenges in systemic delivery, and immunological hurdles. An alternative approach is to repair the patient's own gene. Two innovative small-molecule approaches have emerged as front-line molecular therapeutics: exon skipping and stop codon read through. Both approaches are in human clinical trials and aim to coax dystrophin protein production from otherwise inactive mutant genes. In the clinically severe dog model of Duchenne muscular dystrophy, the exon-skipping approach recently improved multiple functional outcomes. We discuss the status of these two methods aimed at inducing de novo dystrophin production from mutant genes and review implications for other disorders. PMID:21703390

  7. The potential of sarcospan in adhesion complex replacement therapeutics for the treatment of muscular dystrophy

    PubMed Central

    Marshall, Jamie L.; Kwok, Yukwah; McMorran, Brian; Baum, Linda G.; Crosbie-Watson, Rachelle H.

    2013-01-01

    Three adhesion complexes span the sarcolemma and facilitate critical connections between the extracellular matrix and the actin cytoskeleton: the dystrophin- and utrophin-glycoprotein complexes and α7β1 integrin. Loss of individual protein components results in a loss of the entire protein complex and muscular dystrophy. Muscular dystrophy is a progressive, lethal wasting disease characterized by repetitive cycles of myofiber degeneration and regeneration. Protein replacement therapy offers a promising approach for the treatment of muscular dystrophy. Recently, we demonstrated that sarcospan facilitates protein-protein interactions amongst the adhesion complexes and is an important therapeutic target. Here, we review current protein replacement strategies, discuss the potential benefits of sarcospan expression, and identify important experiments that must be addressed for sarcospan to move to the clinic. PMID:23601082

  8. Exercise dependence and the drive for muscularity in male bodybuilders, power lifters, and fitness lifters.

    PubMed

    Hale, Bruce D; Roth, Andrew D; DeLong, Ryan E; Briggs, Michael S

    2010-06-01

    Researchers have hypothesized differences in exercise dependence and drive for muscularity between bodybuilders and power lifters, while others have not found the predicted differences. This study assessed 146 weight lifters (bodybuilders, n=59; power lifters, n=47; fitness lifters, n=40) on the Exercise Dependence Scale, Bodybuilding Dependence Scale, and the Drive for Muscularity Scale. Results showed that bodybuilders and power lifters were significantly higher than fitness lifters on EDS Total, 7 EDS scales, and the 3 BDS scales. In contrast, power lifters were found to be significantly higher on DMS Total and DMS Behavior scales than bodybuilders. The regression results suggest that exercise dependence may be directly related to the drive for muscularity. 2010 Elsevier Ltd. All rights reserved.

  9. Spinal muscular atrophy

    MedlinePlus

    ... and tendons and abnormal curvature of the spine ( scoliosis ). Bracing may be needed. Surgery may be needed to correct skeletal deformities, such as scoliosis. Outlook (Prognosis) Children with SMA type I rarely ...

  10. [Optimal solution and analysis of muscular force during standing balance].

    PubMed

    Wang, Hongrui; Zheng, Hui; Liu, Kun

    2015-02-01

    The present study was aimed at the optimal solution of the main muscular force distribution in the lower extremity during standing balance of human. The movement musculoskeletal system of lower extremity was simplified to a physical model with 3 joints and 9 muscles. Then on the basis of this model, an optimum mathematical model was built up to solve the problem of redundant muscle forces. Particle swarm optimization (PSO) algorithm is used to calculate the single objective and multi-objective problem respectively. The numerical results indicated that the multi-objective optimization could be more reasonable to obtain the distribution and variation of the 9 muscular forces. Finally, the coordination of each muscle group during maintaining standing balance under the passive movement was qualitatively analyzed using the simulation results obtained.

  11. Stem Cell Differentiation Toward the Myogenic Lineage for Muscle Tissue Regeneration: A Focus on Muscular Dystrophy.

    PubMed

    Ostrovidov, Serge; Shi, Xuetao; Sadeghian, Ramin Banan; Salehi, Sahar; Fujie, Toshinori; Bae, Hojae; Ramalingam, Murugan; Khademhosseini, Ali

    2015-12-01

    Skeletal muscle tissue engineering is one of the important ways for regenerating functionally defective muscles. Among the myopathies, the Duchenne muscular dystrophy (DMD) is a progressive disease due to mutations of the dystrophin gene leading to progressive myofiber degeneration with severe symptoms. Although current therapies in muscular dystrophy are still very challenging, important progress has been made in materials science and in cellular technologies with the use of stem cells. It is therefore useful to review these advances and the results obtained in a clinical point of view. This article focuses on the differentiation of stem cells into myoblasts, and their application in muscular dystrophy. After an overview of the different stem cells that can be induced to differentiate into the myogenic lineage, we introduce scaffolding materials used for muscular tissue engineering. We then described some widely used methods to differentiate different types of stem cell into myoblasts. We highlight recent insights obtained in therapies for muscular dystrophy. Finally, we conclude with a discussion on stem cell technology. We discussed in parallel the benefits brought by the evolution of the materials and by the expansion of cell sources which can differentiate into myoblasts. We also discussed on future challenges for clinical applications and how to accelerate the translation from the research to the clinic in the frame of DMD.

  12. Instructions to Adopt an External Focus Enhance Muscular Endurance

    ERIC Educational Resources Information Center

    Marchant, David C.; Greig, Matt; Bullough, Jonathan; Hitchen, Daniel

    2011-01-01

    The influence of internal (movement focus) and external (outcome focus) attentional-focusing instructions on muscular endurance were investigated using three exercise protocols with experienced exercisers. Twenty-three participants completed a maximal repetition, assisted bench-press test on a Smith's machine. An external focus of attention…

  13. Genetic diagnosis of Duchenne and Becker muscular dystrophy using multiplex ligation-dependent probe amplification in Rwandan patients.

    PubMed

    Uwineza, Annette; Hitayezu, Janvier; Murorunkwere, Seraphine; Ndinkabandi, Janvier; Kalala Malu, Celestin Kaputu; Caberg, Jean Hubert; Dideberg, Vinciane; Bours, Vincent; Mutesa, Leon

    2014-04-01

    Duchenne and Becker muscular dystrophies are the most common clinical forms of muscular dystrophies. They are genetically X-linked diseases caused by a mutation in the dystrophin (DMD) gene. A genetic diagnosis was carried out in six Rwandan patients presenting a phenotype of Duchenne and Becker muscular dystrophies and six asymptomatic female carrier relatives using multiplex ligation-dependent probe amplification (MLPA). Our results revealed deletion of the exons 48-51 in one patient, an inherited deletion of the exons 8-21 in two brothers and a de novo deletion of the exons 46-50 in the fourth patient. No copy number variation was found in two patients. Only one female carrier presented exon deletion in the DMD gene. This is the first cohort of genetic analysis in Rwandan patients affected by Duchenne and Becker muscular dystrophies. This report confirmed that MLPA assay can be easily implemented in low-income countries.

  14. Cardiac consequences to skeletal muscle-centric therapeutics for Duchenne muscular dystrophy.

    PubMed

    Townsend, DeWayne; Yasuda, Soichiro; Chamberlain, Jeffrey; Metzger, Joseph M

    2009-02-01

    Duchenne muscular dystrophy (DMD) is a fatal disease of muscle deterioration. Duchenne muscular dystrophy affects all striated muscles in the body, including the heart. Recent advances in palliative care, largely directed at improving respiratory function, have extended life but paradoxically further unmasked emergent heart disease in DMD patients. New experimental strategies have shown promise in restoring dystrophin in the skeletal muscles of dystrophin- deficient animals. These strategies often have little or no capacity for restitution of dystrophin in the hearts of these animals. This article draws on both clinical data and recent experimental data to posit that effective skeletal muscle restricted therapies for DMD will paradoxically heighten cardiomyopathy and heart failure in these patients.

  15. The Mechanosensory Ca2+ Channel as a Central Regulator of Prostate Tumor Cell Migration and Invasiveness

    DTIC Science & Technology

    2008-01-01

    contribute to major human diseases, including muscular dystrophy, kidney disease, cardiac arrhythmias, hyper- tension, and tumor cell invasion...explain why the absence of dystrophin in Duchenne muscular dystrophic muscle results in TRPC1 channels being abnormally gated open (Section VIII.A.3... Muscular Dystrophy BothTRPC1andMscCa are expressed in skeletalmuscle and bothhave been implicated in the muscular degeneration that occurs in Duchenne

  16. Three pledget technique for closure of muscular ventricular septal defects.

    PubMed

    Sharma, Rajesh; Katewa, Ashish

    2012-07-01

    We propose a modification of the simple, horizontal mattress, pledgetted suture technique for closing the small muscular ventricular septal defect (VSD) by interposing an oversized third pledget on the left ventricular (LV) aspect of the defect.

  17. Associations of muscular fitness with psychological positive health, health complaints, and health risk behaviors in Spanish children and adolescents.

    PubMed

    Padilla-Moledo, Carmen; Ruiz, Jonatan R; Ortega, Francisco B; Mora, Jesús; Castro-Piñero, José

    2012-01-01

    We examined the association of muscular fitness with psychological positive health, health complaints, and health risk behaviors in 690 (n = 322 girls) Spanish children and adolescents (6-17.9 years old). Lower body muscular strength was assessed with the standing long jump test, and upper-body muscular strength was assessed with the throw basketball test. A muscular fitness index was computed by means of standardized measures of both tests. Psychosocial positive health, health complaints, and health risk behaviors were self-reported using the items of the Health Behavior in School-aged Children questionnaire. Psychological positive health indicators included the following: perceived health status, life satisfaction, quality of family relationships, quality of peer relationships, and academic performance. We computed a health complaints index from 8 registered symptoms: headache, stomach ache, backache, feeling low, irritability or bad temper, feeling nervous, difficulties getting to sleep, and feeling dizzy. The health risk behavior indicators studied included tobacco use, alcohol use, and getting drunk. Children and adolescents with low muscular fitness (below the mean) had a higher odds ratio (OR) of reporting fair (vs. excellent) perceived health status, low life satisfaction (vs. very happy), low quality of family relationships (vs. very good), and low academic performance (vs. very good). Likewise, children and adolescents having low muscular fitness had a significantly higher OR of reporting smoking tobacco sometimes (vs. never), drinking alcohol sometimes (vs. never), and getting drunk sometimes (vs. never). The results of this study suggest a link between muscular fitness and psychological positive health and health risk behavior indicators in children and adolescents.

  18. Serum Osteopontin as a Novel Biomarker for Muscle Regeneration in Duchenne Muscular Dystrophy.

    PubMed

    Kuraoka, Mutsuki; Kimura, En; Nagata, Tetsuya; Okada, Takashi; Aoki, Yoshitsugu; Tachimori, Hisateru; Yonemoto, Naohiro; Imamura, Michihiro; Takeda, Shin'ichi

    2016-05-01

    Duchenne muscular dystrophy is a lethal X-linked muscle disorder. We have already reported that osteopontin (OPN), an inflammatory cytokine and myogenic factor, is expressed in the early dystrophic phase in canine X-linked muscular dystrophy in Japan, a dystrophic dog model. To further explore the possibility of OPN as a new biomarker for disease activity in Duchenne muscular dystrophy, we monitored serum OPN levels in dystrophic and wild-type dogs at different ages and compared the levels to other serum markers, such as serum creatine kinase, matrix metalloproteinase-9, and tissue inhibitor of metalloproteinase-1. Serum OPN levels in the dystrophic dogs were significantly elevated compared with those in wild-type dogs before and 1 hour after a cesarean section birth and at the age of 3 months. The serum OPN level was significantly correlated with the phenotypic severity of dystrophic dogs at the period corresponding to the onset of muscle weakness, whereas other serum markers including creatine kinase were not. Immunohistologically, OPN was up-regulated in infiltrating macrophages and developmental myosin heavy chain-positive regenerating muscle fibers in the dystrophic dogs, whereas serum OPN was highly elevated. OPN expression was also observed during the synergic muscle regeneration process induced by cardiotoxin injection. In conclusion, OPN is a promising biomarker for muscle regeneration in dystrophic dogs and can be applicable to boys with Duchenne muscular dystrophy. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  19. Trainability of Muscular Activity Level during Maximal Voluntary Co-Contraction: Comparison between Bodybuilders and Nonathletes

    PubMed Central

    Maeo, Sumiaki; Takahashi, Takumi; Takai, Yohei; Kanehisa, Hiroaki

    2013-01-01

    Antagonistic muscle pairs cannot be fully activated simultaneously, even with maximal effort, under conditions of voluntary co-contraction, and their muscular activity levels are always below those during agonist contraction with maximal voluntary effort (MVE). Whether the muscular activity level during the task has trainability remains unclear. The present study examined this issue by comparing the muscular activity level during maximal voluntary co-contraction for highly experienced bodybuilders, who frequently perform voluntary co-contraction in their training programs, with that for untrained individuals (nonathletes). The electromyograms (EMGs) of biceps brachii and triceps brachii muscles during maximal voluntary co-contraction of elbow flexors and extensors were recorded in 11 male bodybuilders and 10 nonathletes, and normalized to the values obtained during the MVE of agonist contraction for each of the corresponding muscles (% EMGMVE). The involuntary coactivation level in antagonist muscle during the MVE of agonist contraction was also calculated. In both muscles, % EMGMVE values during the co-contraction task for bodybuilders were significantly higher (P<0.01) than those for nonathletes (biceps brachii: 66±14% in bodybuilders vs. 46±13% in nonathletes, triceps brachii: 74±16% vs. 57±9%). There was a significant positive correlation between a length of bodybuilding experience and muscular activity level during the co-contraction task (r = 0.653, P = 0.03). Involuntary antagonist coactivation level during MVE of agonist contraction was not different between the two groups. The current result indicates that long-term participation in voluntary co-contraction training progressively enhances muscular activity during maximal voluntary co-contraction. PMID:24260233

  20. Mechanisms and assessment of statin-related muscular adverse effects

    PubMed Central

    Moßhammer, Dirk; Schaeffeler, Elke; Schwab, Matthias; Mörike, Klaus

    2014-01-01

    Statin-associated muscular adverse effects cover a wide range of symptoms, including asymptomatic increase of creatine kinase serum activity and life-threatening rhabdomyolysis. Different underlying pathomechanisms have been proposed. However, a unifying concept of the pathogenesis of statin-related muscular adverse effects has not emerged so far. In this review, we attempt to categorize these mechanisms along three levels. Firstly, among pharmacokinetic factors, it has been shown for some statins that inhibition of cytochrome P450-mediated hepatic biotransformation and hepatic uptake by transporter proteins contribute to an increase of systemic statin concentrations. Secondly, at the myocyte membrane level, cell membrane uptake transporters affect intracellular statin concentrations. Thirdly, at the intracellular level, inhibition of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase results in decreased intracellular concentrations of downstream metabolites (e.g. selenoproteins, ubiquinone, cholesterol) and alteration of gene expression (e.g. ryanodine receptor 3, glycine amidinotransferase). We also review current recommendations for prescribers. PMID:25069381

  1. Patterns of muscular strain in the embryonic heart wall.

    PubMed

    Damon, Brooke J; Rémond, Mathieu C; Bigelow, Michael R; Trusk, Thomas C; Xie, Wenjie; Perucchio, Renato; Sedmera, David; Denslow, Stewart; Thompson, Robert P

    2009-06-01

    The hypothesis that inner layers of contracting muscular tubes undergo greater strain than concentric outer layers was tested by numerical modeling and by confocal microscopy of strain within the wall of the early chick heart. We modeled the looped heart as a thin muscular shell surrounding an inner layer of sponge-like trabeculae by two methods: calculation within a two-dimensional three-variable lumped model and simulated expansion of a three-dimensional, four-layer mesh of finite elements. Analysis of both models, and correlative microscopy of chamber dimensions, sarcomere spacing, and membrane leaks, indicate a gradient of strain decreasing across the wall from highest strain along inner layers. Prediction of wall thickening during expansion was confirmed by ultrasonography of beating hearts. Degree of stretch determined by radial position may thus contribute to observed patterns of regional myocardial conditioning and slowed proliferation, as well as to the morphogenesis of ventricular trabeculae and conduction fascicles. Developmental Dynamics 238:1535-1546, 2009. (c) 2009 Wiley-Liss, Inc.

  2. Using hegemonic masculinity to explain gay male attraction to muscular and athletic men.

    PubMed

    Lanzieri, Nicholas; Hildebrandt, Tom

    2011-01-01

    This article reviews relevant research on male homosexual attraction. Utilizing masculinity as its theoretical frame, the authors use childhood experiences with both fathers and peers, the gay community's inculcation of heteronormative ideologies, and the gay media's adherence to masculine prototypes, to provide causal explanations for the appeal of muscular, lean, and athletic physiques. While the authors acknowledge that not all individuals within the gay community look toward muscularity and athleticism as the primary components of attractiveness, it nonetheless remains important to examine the theoretical perspectives that may explain the appeal of this specific aesthetic.

  3. A current approach to heart failure in Duchenne muscular dystrophy.

    PubMed

    D'Amario, Domenico; Amodeo, Antonio; Adorisio, Rachele; Tiziano, Francesco Danilo; Leone, Antonio Maria; Perri, Gianluigi; Bruno, Piergiorgio; Massetti, Massimo; Ferlini, Alessandra; Pane, Marika; Niccoli, Giampaolo; Porto, Italo; D'Angelo, Gianluca A; Borovac, Josip Anđelo; Mercuri, Eugenio; Crea, Filippo

    2017-11-01

    Duchenne muscular dystrophy (DMD) is a genetic, progressive neuromuscular condition that is marked by the long-term muscle deterioration with significant implications of pulmonary and cardiac dysfunction. As such, end-stage heart failure (HF) in DMD is increasingly becoming the main cause of death in this population. The early detection of cardiomyopathy is often challenging, due to a long subclinical phase of ventricular dysfunction and difficulties in assessment of cardiovascular symptomatology in these patients who usually loose ambulation during the early adolescence. However, an early diagnosis of cardiovascular disease in patients with DMD is decisive since it allows a timely initiation of cardioprotective therapies that can mitigate HF symptoms and delay detrimental heart muscle remodelling. Echocardiography and ECG are standardly used for screening and detection of cardiovascular abnormalities in these patients, although these tools are not always adequate to detect an early, clinically asymptomatic phases of disease progression. In this regard, cardiovascular magnetic resonance (CMR) with late gadolinium enhancement is emerging as a promising method for the detection of early cardiac involvement in patients with DMD. The early detection of cardiac dysfunction allows the therapeutic institution of various classes of drugs such as corticosteroids, beta-blockers, ACE inhibitors, antimineralocorticoid diuretics and novel pharmacological and surgical solutions in the multimodal and multidisciplinary care for this group of patients. This review will focus on these challenges and available options for HF in patients with DMD. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  4. Abnormal pressures as hydrodynamic phenomena

    USGS Publications Warehouse

    Neuzil, C.E.

    1995-01-01

    So-called abnormal pressures, subsurface fluid pressures significantly higher or lower than hydrostatic, have excited speculation about their origin since subsurface exploration first encountered them. Two distinct conceptual models for abnormal pressures have gained currency among earth scientists. The static model sees abnormal pressures generally as relict features preserved by a virtual absence of fluid flow over geologic time. The hydrodynamic model instead envisions abnormal pressures as phenomena in which flow usually plays an important role. This paper develops the theoretical framework for abnormal pressures as hydrodynamic phenomena, shows that it explains the manifold occurrences of abnormal pressures, and examines the implications of this approach. -from Author

  5. The potential of sarcospan in adhesion complex replacement therapeutics for the treatment of muscular dystrophy.

    PubMed

    Marshall, Jamie L; Kwok, Yukwah; McMorran, Brian J; Baum, Linda G; Crosbie-Watson, Rachelle H

    2013-09-01

    Three adhesion complexes span the sarcolemma and facilitate critical connections between the extracellular matrix and the actin cytoskeleton: the dystrophin- and utrophin-glycoprotein complexes and α7β1 integrin. Loss of individual protein components results in a loss of the entire protein complex and muscular dystrophy. Muscular dystrophy is a progressive, lethal wasting disease characterized by repetitive cycles of myofiber degeneration and regeneration. Protein-replacement therapy offers a promising approach for the treatment of muscular dystrophy. Recently, we demonstrated that sarcospan facilitates protein-protein interactions amongst the adhesion complexes and is an important potential therapeutic target. Here, we review current protein-replacement strategies, discuss the potential benefits of sarcospan expression, and identify important experiments that must be addressed for sarcospan to move to the clinic. © 2013 FEBS.

  6. Hydrogel biomaterials and their therapeutic potential for muscle injuries and muscular dystrophies

    PubMed Central

    Lev, Rachel

    2018-01-01

    Muscular diseases such as muscular dystrophies and muscle injuries constitute a large group of ailments that manifest as muscle weakness, atrophy or fibrosis. Although cell therapy is a promising treatment option, the delivery and retention of cells in the muscle is difficult and prevents sustained regeneration needed for adequate functional improvements. Various types of biomaterials with different physical and chemical properties have been developed to improve the delivery of cells and/or growth factors for treating muscle injuries. Hydrogels are a family of materials with distinct advantages for use as cell delivery systems in muscle injuries and ailments, including their mild processing conditions, their similarities to natural tissue extracellular matrix, and their ability to be delivered with less invasive approaches. Moreover, hydrogels can be made to completely degrade in the body, leaving behind their biological payload in a process that can enhance the therapeutic process. For these reasons, hydrogels have shown great potential as cell delivery matrices. This paper reviews a few of the hydrogel systems currently being applied together with cell therapy and/or growth factor delivery to promote the therapeutic repair of muscle injuries and muscle wasting diseases such as muscular dystrophies. PMID:29343633

  7. Is muscular strength balance influenced by menstrual cycle in female soccer players?

    PubMed

    Dos Santos Andrade, Marília; Mascarin, Naryana C; Foster, Roberta; de Jármy di Bella, Zsuzsanna I; Vancini, Rodrigo L; Barbosa de Lira, Claudio A

    2017-06-01

    Muscular strength imbalance is an important risk factor for ACL injury, but it is not clear the impact of menstrual cycle on muscular strength balance. Our aims were to compare muscular balance (hamstring-to-quadriceps peak torque strength balance ratio) between luteal and follicular phases and compare gender differences relative to strength balance to observe possible fluctuations in strength balance ratio. Thirty-eight soccer athletes (26 women and 12 men) took part in this study. Athletes participated in two identical isokinetic strength evaluations for both knee (non-dominant [ND] and dominant [D]). Peak torque for quadriceps and hamstring muscles were measured in concentric mode and hamstring-to-quadriceps peak torque strength balance ratio calculated. Women had significantly lower hamstring-to-quadriceps peak torque strength balance ratio during the follicular compared to luteal phase, for the ND limb (P=0.011). However, no differences, between luteal and follicular phases, were observed in the D limb. In men, no difference in strength balance ratios was found between the ND and D limbs. These data may be useful in prevention programs for knee (ACL) injuries among soccer female athletes.

  8. TNF-α-Induced microRNAs Control Dystrophin Expression in Becker Muscular Dystrophy.

    PubMed

    Fiorillo, Alyson A; Heier, Christopher R; Novak, James S; Tully, Christopher B; Brown, Kristy J; Uaesoontrachoon, Kitipong; Vila, Maria C; Ngheim, Peter P; Bello, Luca; Kornegay, Joe N; Angelini, Corrado; Partridge, Terence A; Nagaraju, Kanneboyina; Hoffman, Eric P

    2015-09-08

    The amount and distribution of dystrophin protein in myofibers and muscle is highly variable in Becker muscular dystrophy and in exon-skipping trials for Duchenne muscular dystrophy. Here, we investigate a molecular basis for this variability. In muscle from Becker patients sharing the same exon 45-47 in-frame deletion, dystrophin levels negatively correlate with microRNAs predicted to target dystrophin. Seven microRNAs inhibit dystrophin expression in vitro, and three are validated in vivo (miR-146b/miR-374a/miR-31). microRNAs are expressed in dystrophic myofibers and increase with age and disease severity. In exon-skipping-treated mdx mice, microRNAs are significantly higher in muscles with low dystrophin rescue. TNF-α increases microRNA levels in vitro whereas NFκB inhibition blocks this in vitro and in vivo. Collectively, these data show that microRNAs contribute to variable dystrophin levels in muscular dystrophy. Our findings suggest a model where chronic inflammation in distinct microenvironments induces pathological microRNAs, initiating a self-sustaining feedback loop that exacerbates disease progression. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  9. Occupational Potential in a Population with Duchenne Muscular Dystrophy.

    ERIC Educational Resources Information Center

    Schkade, Janette K.; And Others

    1987-01-01

    Twenty-five males with Duchenne muscular dystrophy were tested to assess their potential for occupational activity. Tests measured possible sensory deficits, strength, endurance, and fatigue in response to sustained fine motor activity. Results indicate that, within limitations, persons with this diagnosis can engage in activity leading to skill…

  10. Air stacking: effects on pulmonary function in patients with spinal muscular atrophy and in patients with congenital muscular dystrophy*,**

    PubMed Central

    Marques, Tanyse Bahia Carvalho; Neves, Juliana de Carvalho; Portes, Leslie Andrews; Salge, João Marcos; Zanoteli, Edmar; Reed, Umbertina Conti

    2014-01-01

    OBJECTIVE: Respiratory complications are the main causes of morbidity and mortality in patients with neuromuscular disease (NMD). The objectives of this study were to determine the effects that routine daily home air-stacking maneuvers have on pulmonary function in patients with spinal muscular atrophy (SMA) and in patients with congenital muscular dystrophy (CMD), as well as to identify associations between spinal deformities and the effects of the maneuvers. METHODS: Eighteen NMD patients (ten with CMD and eight with SMA) were submitted to routine daily air-stacking maneuvers at home with manual resuscitators for four to six months, undergoing pulmonary function tests before and after that period. The pulmonary function tests included measurements of FVC; PEF; maximum insufflation capacity (MIC); and assisted and unassisted peak cough flow (APCF and UPCF, respectively) with insufflations. RESULTS: After the use of home air-stacking maneuvers, there were improvements in the APCF and UPCF. In the patients without scoliosis, there was also a significant increase in FVC. When comparing patients with and without scoliosis, the increases in APCF and UPCF were more pronounced in those without scoliosis. CONCLUSIONS: Routine daily air-stacking maneuvers with a manual resuscitator appear to increase UPCF and APCF in patients with NMD, especially in those without scoliosis. PMID:25410841

  11. Air stacking: effects on pulmonary function in patients with spinal muscular atrophy and in patients with congenital muscular dystrophy.

    PubMed

    Marques, Tanyse Bahia Carvalho; Neves, Juliana de Carvalho; Portes, Leslie Andrews; Salge, João Marcos; Zanoteli, Edmar; Reed, Umbertina Conti

    2014-10-01

    Respiratory complications are the main causes of morbidity and mortality in patients with neuromuscular disease (NMD). The objectives of this study were to determine the effects that routine daily home air-stacking maneuvers have on pulmonary function in patients with spinal muscular atrophy (SMA) and in patients with congenital muscular dystrophy (CMD), as well as to identify associations between spinal deformities and the effects of the maneuvers. Eighteen NMD patients (ten with CMD and eight with SMA) were submitted to routine daily air-stacking maneuvers at home with manual resuscitators for four to six months, undergoing pulmonary function tests before and after that period. The pulmonary function tests included measurements of FVC; PEF; maximum insufflation capacity (MIC); and assisted and unassisted peak cough flow (APCF and UPCF, respectively) with insufflations. After the use of home air-stacking maneuvers, there were improvements in the APCF and UPCF. In the patients without scoliosis, there was also a significant increase in FVC. When comparing patients with and without scoliosis, the increases in APCF and UPCF were more pronounced in those without scoliosis. Routine daily air-stacking maneuvers with a manual resuscitator appear to increase UPCF and APCF in patients with NMD, especially in those without scoliosis.

  12. High-Pressure Transvenous Perfusion of the Upper Extremity in Human Muscular Dystrophy: A Safety Study with 0.9% Saline.

    PubMed

    Fan, Zheng; Kocis, Keith; Valley, Robert; Howard, James F; Chopra, Manisha; Chen, Yasheng; An, Hongyu; Lin, Weili; Muenzer, Joseph; Powers, William

    2015-09-01

    We evaluated safety and feasibility of high-pressure transvenous limb perfusion in an upper extremity of adult patients with muscular dystrophy, after completing a similar study in a lower extremity. A dose escalation study of single-limb perfusion with 0.9% saline was carried out in nine adults with muscular dystrophies under intravenous analgesia. Our study demonstrates that it is feasible and definitely safe to perform high-pressure transvenous perfusion with 0.9% saline up to 35% of limb volume in the upper extremities of young adults with muscular dystrophy. Perfusion at 40% limb volume is associated with short-lived physiological changes in peripheral nerves without clinical correlates in one subject. This study provides the basis for a phase 1/2 clinical trial using pressurized transvenous delivery into upper limbs of nonambulatory patients with Duchenne muscular dystrophy. Furthermore, our results are applicable to other conditions such as limb girdle muscular dystrophy as a method for delivering regional macromolecular therapeutics in high dose to skeletal muscles of the upper extremity.

  13. Clinical Manifestations and Overall Management Strategies for Duchenne Muscular Dystrophy.

    PubMed

    Tsuda, Takeshi

    2018-01-01

    Duchenne muscular dystrophy (DMD) is an X-linked genetic disorder that causes progressive weakness and wasting of skeletal muscular and myocardium in boys due to mutation of dystrophin. The structural integrity of each individual skeletal and cardiac myocyte is significantly compromised upon physical stress due to the absence of dystrophin. The progressive destruction of systemic musculature and myocardium causes affected patients to develop multiple organ disabilities, including loss of ambulation, physical immobility, neuromuscular scoliosis, joint contracture, restrictive lung disease, obstructive sleep apnea, and cardiomyopathy. There are some central nervous system-related medical problems, as dystrophin is also expressed in the neuronal tissues. Although principal management is to mainly delay the pathological process, an enhanced understanding of underlying pathological processes has significantly improved quality of life and longevity for DMD patients. Future research in novel molecular approach is warranted to answer unanswered questions.

  14. Effectiveness of a Brief Intervention Using Process-Based Mental Simulations in Promoting Muscular Strength in Physical Education

    ERIC Educational Resources Information Center

    Koka, Andre

    2017-01-01

    This study examined the effectiveness of a brief theory-based intervention on muscular strength among adolescents in a physical education setting. The intervention adopted a process-based mental simulation technique. The self-reported frequency of practising for and actual levels of abdominal muscular strength/endurance as one component of…

  15. [Two cases of Duchenne muscular dystrophy over 40 years after onset].

    PubMed

    Ishizaki, Masatoshi; Ueyama, Hidetsugu; Masuda, Teruaki; Nishida, Yasuto; Imamura, Shigehiro; Ando, Yukio

    2013-01-01

    We report two 45 year old men with Duchenne muscular dystrophy. Case 1 showed a deleted exon 50 of the dystrophin gene by MLPA analysis, and Case 2 showed deleted exons 46-52. Both patients presented with severe weakness of the skeletal muscles and respiratory dysfunction, while cardiac involvement was mild and cognitive function was almost normal. The patients are able to shop at a mall, participate in activities, and attend hobbies, although they are bedridden with artificial respiration through tracheotomy. With the progress of the respiratory care and cardiac protective therapy, the prognosis of Duchenne muscular dystrophy has improved remarkably. At present, it is possible to survive over 40 years with maintenance of quality of life, if cardiac damage is not severe.

  16. Spinal Muscular Atrophy With Respiratory Distress Type 1-A Child With Atypical Presentation.

    PubMed

    Chiu, Annie Ting Gee; Chan, Sophelia Hoi Shan; Wu, Shun Ping; Ting, Shun Hin; Chung, Brian Hon Yin; Chan, Angel On Kei; Wong, Virginia Chun Nei

    2018-01-01

    The authors report a child with spinal muscular atrophy with respiratory distress type 1 (SMARD1). She presented atypically with hypothyroidism and heart failure due to septal defects that required early heart surgery and microcephaly in association with cerebral atrophy and thin corpus collosum. The subsequent asymmetrical onset of diaphragmatic paralysis, persistent hypotonia, and generalized muscle weakness led to the suspicion of spinal muscular atrophy with respiratory distress type 1. Sanger sequencing confirmed a compound heterozygous mutation in the Immunoglobulin Mu Binding Protein 2 (IGHMBP2) gene, with a known mutation c.2362C > T (p.Arg788*) and a novel frameshift mutation c.2048delG (p.Gly683A1afs*50). Serial nerve conduction study and electromyography confirmed progressive sensorimotor polyneuropathy and neuronopathy. In summary, this case report describes a child with spinal muscular atrophy with respiratory distress type 1 also with congenital cardiac disease and endocrine dysfunction, expanding the phenotypic spectrum of this condition. A high index of suspicion is needed in diagnosing this rare condition to guide the management and genetic counseling.

  17. Evaluation of 1100 couples with recurrent pregnancy loss using conventional cytogenetic, PGD, and PGS: hype or hope.

    PubMed

    Farahmand, Kamelia; Kalantari, Hamid; Fakhri, Mostafa; Fazeli, Abolhasan Shahzadeh; Moradi, Shabnam Zari; Almadani, Navid; Hashemi, Mehrdad; Gourabi, Hamid; Mohseni-Meybodi, Anahita

    2016-06-01

    Recurrent pregnancy loss (RPL) is an important clinical problem, mostly resulting from chromosomal or genetic defects, while in 30-60% of cases, it is idiopathic. The aim of this study is to evaluate the frequency and types of chromosomal abnormalities, also pre-implantation genetic diagnosis (PGD) and pre-implantation genetic screening (PGS) outcomes among Iranian couples with RPL. This retrospective study was conducted on 1100 Iranian couples (2200 individuals) with RPL referred to Royan Institute between 2008 and 2014. Karyotyping had been performed using standard cytogenetic techniques. PGD results of RPL patients with abnormal karyotypes and PGS results of RPL patients with normal karyotypes were also analyzed. The frequency of chromosomal abnormalities in these patients was 4.95%. Women demonstrated more abnormalities (6.82%) in comparison to men (3.09%). The successful rate of pregnancy after PGD and PGS was 52 and 18.64%, respectively. The observation of 4.95% chromosomal abnormalities among the patients with RPL could support this hypothesis that there is a direct relationship between chromosomal abnormalities and RPL. More than half of the patients who underwent PGD had successful pregnancy; therefore, this approach can improve the success rate of pregnancy in them. The results of PGS cycles showed that this technique could increase the live birth rate in RPL patients.

  18. Histopathological Evaluation of Skeletal Muscle with Specific Reference to Mouse Models of Muscular Dystrophy.

    PubMed

    Terry, Rebecca L; Wells, Dominic J

    2016-12-01

    The muscular dystrophies are a diverse group of degenerative diseases for which many mouse models are available. These models are frequently used to assess potential therapeutic interventions and histological evaluation of multiple muscles is an important part of this assessment. Histological evaluation is especially useful when combined with tests of muscle function. This unit describes a protocol for necropsy, processing, cryosectioning, and histopathological evaluation of murine skeletal muscles, which is applicable to both models of muscular dystrophy and other neuromuscular conditions. Key histopathological features of dystrophic muscle are discussed using the mdx mouse (a model of Duchenne muscular dystrophy) as an example. Optimal handling during dissection, processing and sectioning is vital to avoid artifacts that can confound or prevent future analyses. Muscles carefully processed using this protocol are suitable for further evaluation using immunohistochemistry, immunofluorescence, special histochemical stains, and immuoblotting. © 2016 by John Wiley & Sons, Inc. Copyright © 2016 John Wiley & Sons, Inc.

  19. Is There a Delay in Diagnosis of Duchenne Muscular Dystrophy Among Preterm-Born Males?

    PubMed

    Soim, Aida; Smith, Michael G; Kwon, Jennifer M; Mann, Joshua R; Thomas, Shiny; Ciafaloni, Emma

    2018-07-01

    The objective of this study was to investigate whether males who were born preterm took longer to receive a Duchenne muscular dystrophy diagnosis than term males. Data for males with Duchenne muscular dystrophy identified through a population-based surveillance system were analyzed using a Kaplan-Meier estimator. The first signs and symptoms were noted at a median age of 2 years in both groups. Median age when first signs and symptoms prompted medical evaluation was 2.59 years among preterm and 4.01 years among term males. Median age at definitive diagnosis was 4.25 years and 4.92 years for preterm and term males, respectively. Neither difference was statistically significant. Preterm males tended to be seen for their initial medical evaluation earlier than term males, though they were not diagnosed significantly earlier. It may take clinicians longer after the initial evaluation of preterm males to arrive at a Duchenne muscular dystrophy diagnosis.

  20. The onset and evolution of fatigue-induced abnormal grain growth in nanocrystalline Ni–Fe

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Furnish, T. A.; Mehta, A.; Van Campen, D.

    Conventional structural metals suffer from fatigue-crack initiation through dislocation activity which forms persistent slip bands leading to notch-like extrusions and intrusions. Ultrafine-grained and nanocrystalline metals can potentially exhibit superior fatigue-crack initiation resistance by suppressing these cumulative dislocation activities. Prior studies on these metals have confirmed improved high-cycle fatigue performance. In the case of nano-grained metals, analyses of subsurface crack initiation sites have indicated that the crack nucleation is associated with abnormally large grains. But, these post-mortem analyses have led to only speculation about when abnormal grain growth occurs (e.g., during fatigue, after crack initiation, or during crack growth). In thismore » study, a recently developed synchrotron X-ray diffraction technique was used to detect the onset and progression of abnormal grain growth during stress-controlled fatigue loading. Our study provides the first direct evidence that the grain coarsening is cyclically induced and occurs well before final fatigue failure—our results indicate that the first half of the fatigue life was spent prior to the detectable onset of abnormal grain growth, while the second half was spent coarsening the nanocrystalline structure and cyclically deforming the abnormally large grains until crack initiation. Post-mortem fractography, coupled with cycle-dependent diffraction data, provides the first details regarding the kinetics of this abnormal grain growth process during high-cycle fatigue testing. Finally, precession electron diffraction images collected in a transmission electron microscope after the in situ fatigue experiment also confirm the X-ray evidence that the abnormally large grains contain substantial misorientation gradients and sub-grain boundaries.« less

  1. The onset and evolution of fatigue-induced abnormal grain growth in nanocrystalline Ni–Fe

    DOE PAGES

    Furnish, T. A.; Mehta, A.; Van Campen, D.; ...

    2016-10-11

    Conventional structural metals suffer from fatigue-crack initiation through dislocation activity which forms persistent slip bands leading to notch-like extrusions and intrusions. Ultrafine-grained and nanocrystalline metals can potentially exhibit superior fatigue-crack initiation resistance by suppressing these cumulative dislocation activities. Prior studies on these metals have confirmed improved high-cycle fatigue performance. In the case of nano-grained metals, analyses of subsurface crack initiation sites have indicated that the crack nucleation is associated with abnormally large grains. But, these post-mortem analyses have led to only speculation about when abnormal grain growth occurs (e.g., during fatigue, after crack initiation, or during crack growth). In thismore » study, a recently developed synchrotron X-ray diffraction technique was used to detect the onset and progression of abnormal grain growth during stress-controlled fatigue loading. Our study provides the first direct evidence that the grain coarsening is cyclically induced and occurs well before final fatigue failure—our results indicate that the first half of the fatigue life was spent prior to the detectable onset of abnormal grain growth, while the second half was spent coarsening the nanocrystalline structure and cyclically deforming the abnormally large grains until crack initiation. Post-mortem fractography, coupled with cycle-dependent diffraction data, provides the first details regarding the kinetics of this abnormal grain growth process during high-cycle fatigue testing. Finally, precession electron diffraction images collected in a transmission electron microscope after the in situ fatigue experiment also confirm the X-ray evidence that the abnormally large grains contain substantial misorientation gradients and sub-grain boundaries.« less

  2. Effect of Resistance Training Frequency on Gains in Muscular Strength: A Systematic Review and Meta-Analysis.

    PubMed

    Grgic, Jozo; Schoenfeld, Brad J; Davies, Timothy B; Lazinica, Bruno; Krieger, James W; Pedisic, Zeljko

    2018-05-01

    Current recommendations on resistance training (RT) frequency for gains in muscular strength are based on extrapolations from limited evidence on the topic, and thus their practical applicability remains questionable. To elucidate this issue, we conducted a systematic review and meta-analysis of the studies that compared muscular strength outcomes with different RT frequencies. To carry out this review, English-language literature searches of the PubMed/MEDLINE, Scopus, and SPORTDiscus databases were conducted. The meta-analysis was performed using a random-effects model. The meta-analysis models were generated with RT frequencies classified as a categorical variable as either 1, 2, 3, or 4+ times/week, or, if there were insufficient data in subgroup analyses, the training frequencies were categorized as 1, 2, or 3 times/week. Subgroup analyses were performed for potential moderators, including (1) training volume; (2) exercise selection for the 1 repetition maximum (RM) test (for both multi-joint and single-joint exercises); (3) upper and lower body strength gains; (4) training to muscular failure (for studies involving and not involving training to muscular failure); (5) age (for both middle-aged/older adults and young adults); and (6) sex (for men and for women). The methodological quality of studies was appraised using the modified Downs and Black checklist. A total of 22 studies were found to meet the inclusion criteria. The average score on the Downs and Black checklist was 18 (range 13-22 points). Four studies were classified as being of good methodological quality, while the rest were classified as being of moderate methodological quality. Results of the meta-analysis showed a significant effect (p = 0.003) of RT frequency on muscular strength gains. Effect sizes increased in magnitude from 0.74, 0.82, 0.93, and 1.08 for training 1, 2, 3, and 4+ times per week, respectively. A subgroup analysis of volume-equated studies showed no significant effect (p

  3. What Can DuchenneConnect Teach Us About Treating Duchenne Muscular Dystrophy?

    PubMed Central

    Wang, Richard T; Nelson, Stanley F

    2015-01-01

    Purpose of Review This review aims to describe the benefits and limitations of using the DuchenneConnect patient registry to provide information particularly in regard to active treatment choices in Duchenne muscular dystrophy and their impact on disease progression. Recent findings Clinical trials and natural history studies are difficult for rare diseases like Duchenne muscular dystrophy. Using an online patient self-report survey model, DuchenneConnect provides relevant data that are difficult to gather in other ways. Validation of the overall dataset is supported by comparable mutational spectrum relative to other cohorts and demonstrated beneficial effect of corticosteroid use in prolonging ambulation. These types of analyses are provocative and allow multivariate analyses across the breadth of patient and physician medication and supplement practices. Because the data is self-reported and online, the barrier to participation is low and great potential exists for novel directions of further research in a highly participatory forum. Summary Patient registries for Duchenne and Becker muscular dystrophy are powerful tools for monitoring patient outcomes, comparing treatments options, and relating information between patients, researchers and clinicians. DuchenneConnect is an online patient self-report registry for individuals with DBMD that facilitates aggregation of treatment modalities, outcomes and genotype data and has played a vital role in furthering DBMD research, particularly in the US, in a highly participatory and low cost manner. PMID:26356412

  4. The associations between increasing degrees of homeostatic model assessment for insulin resistance and muscular strengthening activities among euglycaemic US adults.

    PubMed

    Boyer, William R; Johnson, Tammie M; Fitzhugh, Eugene C; Richardson, Michael R; Churilla, James R

    2015-11-01

    To examine the associations between the homeostatic model assessment for insulin resistance and self-reported muscular strengthening activity in a nationally representative sample of euglycaemic US adults. Sample included euglycaemic adults (⩾20 years of age (n = 2009)) from the 1999 to 2004 National Health and Nutrition Examination Survey. Homeostatic model assessment for insulin resistance was categorized into quartiles and was the primary independent variable of interest. No reported muscular strengthening activity was the dependent variable. Following adjustment for covariates, those with homeostatic model assessment for insulin resistance values in fourth (odds ratio: 2.04, 95% confidence interval: 1.35-3.06, p < 0.001) quartile were found to have significantly greater odds of reporting no muscular strengthening activity. Following further adjustment for non-muscular strengthening activity specific aerobic leisure-time physical activity, results remained significant for the fourth (odds ratio: 2.30, 95% confidence interval: 1.50-3.52, p < 0.001) quartile. A significant trend was seen across quartiles of homeostatic model assessment for insulin resistance for increasing prevalence of no muscular strengthening activity (p < 0.001). Having a higher homeostatic model assessment for insulin resistance value is associated with greater odds of reporting no muscular strengthening activity among euglycaemic US adults. This implies that subjects with an increasing degree of insulin resistance are more likely to not engage in muscular strengthening activity, an exercise modality that has been shown to reduce the risk of several cardiometabolic diseases and improve glycaemic status. © The Author(s) 2015.

  5. Abnormal pressure in hydrocarbon environments

    USGS Publications Warehouse

    Law, B.E.; Spencer, C.W.

    1998-01-01

    Abnormal pressures, pressures above or below hydrostatic pressures, occur on all continents in a wide range of geological conditions. According to a survey of published literature on abnormal pressures, compaction disequilibrium and hydrocarbon generation are the two most commonly cited causes of abnormally high pressure in petroleum provinces. In young (Tertiary) deltaic sequences, compaction disequilibrium is the dominant cause of abnormal pressure. In older (pre-Tertiary) lithified rocks, hydrocarbon generation, aquathermal expansion, and tectonics are most often cited as the causes of abnormal pressure. The association of abnormal pressures with hydrocarbon accumulations is statistically significant. Within abnormally pressured reservoirs, empirical evidence indicates that the bulk of economically recoverable oil and gas occurs in reservoirs with pressure gradients less than 0.75 psi/ft (17.4 kPa/m) and there is very little production potential from reservoirs that exceed 0.85 psi/ft (19.6 kPa/m). Abnormally pressured rocks are also commonly associated with unconventional gas accumulations where the pressuring phase is gas of either a thermal or microbial origin. In underpressured, thermally mature rocks, the affected reservoirs have most often experienced a significant cooling history and probably evolved from an originally overpressured system.

  6. Associations between aerobic and muscular fitness and cardiovascular disease risk: the northern Ireland young hearts study.

    PubMed

    Hoekstra, Trynke; Boreham, Colin A; Murray, Liam J; Twisk, Jos W R

    2008-11-01

    It is not clear what the relative contribution is of specific components of physical fitness (aerobic and muscular) to cardiovascular disease (CVD) risk. We investigated associations between aerobic fitness (endurance) and muscular fitness (power) and CVD risk factors. Data were obtained from the Young Hearts project, a representative sample of 12- and 15-year-old boys and girls from Northern Ireland (N = 2016). Aerobic fitness was determined by the 20-m shuttle run test, muscular fitness by the Sargent jump test. CVD risk factors included sum of skinfolds, systolic and diastolic blood pressure, serum total cholesterol (TC), HDL cholesterol, and TC:HDL ratio. Several linear regression analyses were conducted for 4 age and gender groups separately, with the risk factor as the outcome variable. Significant associations between aerobic fitness and a healthy CVD risk profile were found. These observed relationships were independent of power, whereas the (few) relationships between muscular fitness and the risk factors were partly explained by endurance. Tailored, preventive strategies during adolescence, incorporating endurance rather than power sports, could be encouraged to help prevent CVD. This is important because existing studies propose that healthiness during adulthood is founded on healthiness in adolescence.

  7. Glucose Metabolism as a Pre-clinical Biomarker for the Golden Retriever Model of Duchenne Muscular Dystrophy.

    PubMed

    Schneider, Sarah Morar; Sridhar, Vidya; Bettis, Amanda K; Heath-Barnett, Heather; Balog-Alvarez, Cynthia J; Guo, Lee-Jae; Johnson, Rachel; Jaques, Scott; Vitha, Stanislav; Glowcwski, Alan C; Kornegay, Joe N; Nghiem, Peter P

    2018-03-05

    Metabolic dysfunction in Duchenne muscular dystrophy (DMD) is characterized by reduced glycolytic and oxidative enzymes, decreased and abnormal mitochondria, decreased ATP, and increased oxidative stress. We analyzed glucose metabolism as a potential disease biomarker in the genetically homologous golden retriever muscular dystrophy (GRMD) dog with molecular, biochemical, and in vivo imaging. Pelvic limb skeletal muscle and left ventricle tissue from the heart were analyzed by mRNA profiling, qPCR, western blotting, and immunofluorescence microscopy for the primary glucose transporter (GLUT4). Physiologic glucose handling was measured by fasting glucose tolerance test (GTT), insulin levels, and skeletal and cardiac positron emission tomography/X-ray computed tomography (PET/CT) using the glucose analog 2-deoxy-2-[ 18 F]fluoro-D-glucose ([ 18 F]FDG). MRNA profiles showed decreased GLUT4 in the cranial sartorius (CS), vastus lateralis (VL), and long digital extensor (LDE) of GRMD vs. normal dogs. QPCR confirmed GLUT4 downregulation but increased hexokinase-1. GLUT4 protein levels were not different in the CS, VL, or left ventricle but increased in the LDE of GRMD vs. normal. Microscopy revealed diffuse membrane expression of GLUT4 in GRMD skeletal but not cardiac muscle. GTT showed higher basal glucose and insulin in GRMD but rapid tissue glucose uptake at 5 min post-dextrose injection in GRMD vs. normal/carrier dogs. PET/ CT with [ 18 F]FDG and simultaneous insulin stimulation showed a significant increase (p = 0.03) in mean standard uptake values (SUV) in GRMD skeletal muscle but not pelvic fat at 5 min post-[ 18 F]FDG /insulin injection. Conversely, mean cardiac SUV was lower in GRMD than carrier/normal (p < 0.01). Altered glucose metabolism in skeletal and cardiac muscle of GRMD dogs can be monitored with molecular, biochemical, and in vivo imaging studies and potentially utilized as a biomarker for disease progression and therapeutic response.

  8. An Overview of Recent Therapeutics Advances for Duchenne Muscular Dystrophy.

    PubMed

    Mah, Jean K

    2018-01-01

    Duchenne muscular dystrophy (DMD) is the most common form of muscular dystrophy in childhood. Mutations of the DMD gene destabilize the dystrophin associated glycoprotein complex in the sarcolemma. Ongoing mechanical stress leads to unregulated influx of calcium ions into the sarcoplasm, with activation of proteases, release of proinflammatory cytokines, and mitochondrial dysfunction. Cumulative damage and reparative failure leads to progressive muscle necrosis, fibrosis, and fatty replacement. Although there is presently no cure for DMD, scientific advances have led to many potential disease-modifying treatments, including dystrophin replacement therapies, upregulation of compensatory proteins, anti-inflammatory agents, and other cellular targets. Recently approved therapies include ataluren for stop codon read-through and eteplirsen for exon 51 skipping of eligible individuals. The purpose of this chapter is to summarize the clinical features of DMD, to describe current outcome measures used in clinical studies, and to highlight new emerging therapies for affected individuals.

  9. Muscular fatigue in response to different modalities of CrossFit sessions

    PubMed Central

    Maté-Muñoz, José Luis; Lougedo, Juan H.; Barba, Manuel; García-Fernández, Pablo

    2017-01-01

    Background CrossFit is a new strength and conditioning regimen involving short intense daily workouts called workouts of the day (WOD). This study assesses muscular fatigue levels induced by the three modalities of CrossFit WOD; gymnastics (G), metabolic conditioning (M) and weightlifting (W). Material and methods 34 healthy subjects undertook three WOD (one per week): a G WOD consisting of completing the highest number of sets of 5 pull-ups, 10 push-ups and 15 air squats in 20 min; an M WOD, in which the maximum number of double skipping rope jumps was executed in 8 sets (20 s), resting (10 s) between sets; and finally, a W WOD in which the maximum number of power cleans was executed in 5 min, lifting a load equivalent to 40% of the individual's 1RM. Before and after each WOD, blood lactate concentrations were measured. Also, before, during, and after each WOD, muscular fatigue was assessed in a countermovement jump test (CMJ). Results Significant reductions were produced in the mechanical variables jump height, average power and maximum velocity in response to G; and in jump height, mean and peak power, maximum velocity and maximum force in response to W (P<0.01). However, in M, significant reductions in mechanical variables were observed between pre- and mid session (after sets 2, 4, 6 and 8), but not between pre- and post session. Conclusions Muscular fatigue, reflected by reduced CMJ variables, was produced following the G and W sessions, while recovery of this fatigue was observed at the end of M, likely attributable to rest intervals allowing for the recovery of phosphocreatine stores. Our findings also suggest that the high intensity and volume of exercise in G and W WODs could lead to reduced muscular-tendon stiffness causing a loss of jump ability, related here to a longer isometric phase during the CMJ. PMID:28753624

  10. The muscular dystrophies associated with central nervous system lesions: a brief review from a standpoint of the localization and function of causative genes.

    PubMed

    Yamamoto, Tomoko; Hiroi, Atsuko; Osawa, Makiko; Shibata, Noriyuki

    2014-01-01

    The muscular dystrophies have been traditionally classified based mainly on clinical manifestation and mode of inheritance. Owing to the discoveries of causative genes, new terminologies derived from each gene, such as dystrophinopathy, α-dystroglycanopathy, sarcoglycanopathy and fukutinopathy, have also become common. Mutations of each gene may cause several clinical phenotypes. Some muscular dystrophies accompany central nervous system (CNS) lesions, especially in the congenital muscular dystrophies. Cobblestone lissencephaly (type II lissencephaly) is a well-known CNS malformation observed in severe forms of α-dystroglycanopathy. Moreover, CNS involvement has been reported in other muscular dystrophies, such as Duchenne muscular dystrophy. In this review, genes related to the muscular dystrophies associated with CNS lesions are briefly described along with the molecular characteristics of each gene and the pathomechanism of the CNS lesions. Understanding of both the clinicopathological characteristics of these CNS lesions and their molecular mechanisms is important for the diagnosis, care of patients, and development of new therapeutic strategies.

  11. Instructional Constraints Faced by Learners with Muscular Dystrophy: A Case of Joytown Special Primary School, Thika, Kenya

    ERIC Educational Resources Information Center

    Wang'ang'a, Annrose Wanjiku; Wamocho, Franciscah Irangi; Kioy, Paul

    2015-01-01

    The purpose of this study was to investigate the instructional constraints facing learners with muscular dystrophy in Joy Town special primary school, Thika, Kenya. Descriptive design was used for this study. The target population were all the 20 learners suffering from muscular dystrophy from S.A Joy Town Special Primary School. The total target…

  12. Sensorimotor integration and psychopathology: motor control abnormalities related to psychiatric disorders.

    PubMed

    Velasques, Bruna; Machado, Sergio; Paes, Flávia; Cunha, Marlo; Sanfim, Antonio; Budde, Henning; Cagy, Mauricio; Anghinah, Renato; Basile, Luis F; Piedade, Roberto; Ribeiro, Pedro

    2011-12-01

    Recent evidence is reviewed to examine relationships among sensorimotor and cognitive aspects in some important psychiatry disorders. This study reviews the theoretical models in the context of sensorimotor integration and the abnormalities reported in the most common psychiatric disorders, such as Alzheimer's disease, autism spectrum disorder and squizophrenia. The bibliographical search used Pubmed/Medline, ISI Web of Knowledge, Cochrane data base and Scielo databases. The terms chosen for the search were: Alzheimer's disease, AD, autism spectrum disorder, and Squizophrenia in combination with sensorimotor integration. Fifty articles published in English and were selected conducted from 1989 up to 2010. We found that the sensorimotor integration process plays a relevant role in elementary mechanisms involved in occurrence of abnormalities in most common psychiatric disorders, participating in the acquisition of abilities that have as critical factor the coupling of different sensory data which will constitute the basis of elaboration of consciously goal-directed motor outputs. Whether these disorders are associated with an abnormal peripheral sensory input or defective central processing is still unclear, but some studies support a central mechanism. Sensorimotor integration seems to play a significant role in the disturbances of motor control, like deficits in the feedforward mechanism, typically seen in AD, autistic and squizophrenic patients.

  13. Assessment of Muscular Fitness as a Predictor of Flight Duty Limitation.

    PubMed

    Honkanen, Tuomas; Mäntysaari, Matti; Avela, Janne; Kyröläinen, Heikki; Leino, Tuomo

    2018-05-08

    The high acceleration (Gz) exposure among military pilots flying fighter aircraft has been associated with an increased risk for cervical and lumbar disorders. It has been suggested that an adequate level of physical performance could reduce the risk of experiencing these disorders. The Finnish Air Force has for several years used aerobic (bicycle ergometer) and muscular fitness tests (battery of five tests) in the selection process of military pilot candidates in order to evaluate their physical fitness level. The aim of the study was to determine if these selection phase tests and anthropometry measures can predispose those individuals who might be at risk of developing severe spinal disorders leading to permanent flight duty limitations later during their military pilots' career. The study population consisted of 23 pilots flying with Gz limitation (+2 Gz, +4 Gz or +5 Gz) due to spinal disorders and 50 experienced (+1,000 flight hours) symptomless controls flying actively in operative missions. Data obtained retrospectively for all subjects included anthropometry, physical (aerobic and muscular fitness) test results and self-reported physical activity levels at a pilot selection phase. Aerobic fitness was measured with a maximal ergometer test and muscular endurance was evaluated with a test battery (standing long jump, pull-ups, sit-ups, back extensions, and push-up tests). Fighter pilots flying without Gz limitation had significantly better mean (±SE) results in pull-up (14.4 ± 4.2 vs. 11.5 ± 2.0, p < 0.05) and back extension (71.1 ± 14.1 vs. 60.0 ± 12.2, p < 0.05) tests during the pilot selection when compared with the limited pilots. Similarly, the non-limited pilots had a better total muscular fitness test score (13.7 ± 1.7 vs. 12.4 ± 1.6, p < 0.05) during the pilot selection. They had also participated in significantly more competitive sports (54% vs. 22%, p < 0.05) at the time of selection when compared with pilots flying with Gz limitation due to

  14. [Upper limb functional assessment scale for children with Duchenne muscular dystrophy and Spinal muscular atrophy].

    PubMed

    Escobar, Raúl G; Lucero, Nayadet; Solares, Carmen; Espinoza, Victoria; Moscoso, Odalie; Olguín, Polín; Muñoz, Karin T; Rosas, Ricardo

    2016-08-16

    Duchenne muscular dystrophy (DMD) and Spinal muscular atrophy (SMA) causes significant disability and progressive functional impairment. Readily available instruments that assess functionality, especially in advanced stages of the disease, are required to monitor the progress of the disease and the impact of therapeutic interventions. To describe the development of a scale to evaluate upper limb function (UL) in patients with DMD and SMA, and describe its validation process, which includes self-training for evaluators. The development of the scale included a review of published scales, an exploratory application of a pilot scale in healthy children and those with DMD, self-training of evaluators in applying the scale using a handbook and video tutorial, and assessment of a group of children with DMD and SMA using the final scale. Reliability was assessed using Cronbach and Kendall concordance and with intra and inter-rater test-retest, and validity with concordance and factorial analysis. A high level of reliability was observed, with high internal consistency (Cronbach α=0.97), and inter-rater (Kendall W=0.96) and intra-rater concordance (r=0.97 to 0.99). The validity was demonstrated by the absence of significant differences between results by different evaluators with an expert evaluator (F=0.023, P>.5), and by the factor analysis that showed that four factors account for 85.44% of total variance. This scale is a reliable and valid tool for assessing UL functionality in children with DMD and SMA. It is also easily implementable due to the possibility of self-training and the use of simple and inexpensive materials. Copyright © 2016 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  15. Characteristics of Japanese Patients with Becker Muscular Dystrophy and Intermediate Muscular Dystrophy in a Japanese National Registry of Muscular Dystrophy (Remudy): Heterogeneity and Clinical Variation.

    PubMed

    Mori-Yoshimura, Madoka; Mitsuhashi, Satomi; Nakamura, Harumasa; Komaki, Hirofumi; Goto, Kanako; Yonemoto, Naohiro; Takeuchi, Fumi; Hayashi, Yukiko K; Murata, Miho; Takahashi, Yuji; Nishino, Ichizo; Takeda, Shin'ichi; Kimura, En

    2018-01-01

    Obtaining an adequate number of patients to conduct a natural history study for rare diseases such as Becker muscular dystrophy (BMD) is difficult. The present study used data from Remudy, a national registry for neuromuscular diseases in Japan, to conduct a phenotypic analysis of BMD. We analyzed Remudy data of participants with dystrophinopathy. All participants who were aged 17 and older and were ambulant at age 13 were included in this study. Participants were divided into two groups: those with BMD who were ambulant at age 17, and those with intermediate muscular dystrophy (IMD) who lost ambulation by age 17. Frequent mutations were analyzed by age at ambulation, cardiopulmonary function, and genotype. For clinical comparisons, participants who were administered steroids were excluded. From July 2009 through September 2015, 192 participants had registered with Remudy. Mean participant age was 34.80±13.3 (range, 17-78) years, and 52.1% of participants were ambulant. Of the entire study population, 50.5% had cardiomyopathy and 35.9% had respiratory failure. Three participants required invasive ventilation and 30 required non-invasive ventilation. Nineteen of the 30 non-invasive ventilator users were part-time users. In total, 138 (71.9%) had BMD and 54 (28.1%) had IMD. The most frequent mutation was ex45_ex47del (36 participants). Among participants with frequent in-frame mutations, those with the ex45-49del mutation lost their ambulation earlier than those with the ex45_ex47del mutation. A total of 67 different exon deletions and duplications were identified in the study population. We clarified the clinical phenotypes of Japanese patients with BMD/IMD using data from Remudy. Our results suggest that not only IMD but also BMD are associated with risk of respiratory dysfunction.

  16. Standard Operating Procedures (SOPs) for Evaluating the Heart in Preclinical Studies of Duchenne Muscular Dystrophy.

    PubMed

    Duan, Dongsheng; Rafael-Fortney, Jill A; Blain, Alison; Kass, David A; McNally, Elizabeth M; Metzger, Joseph M; Spurney, Christopher F; Kinnett, Kathi

    2016-02-01

    A recent working group meeting focused on contemporary cardiac issues in Duchenne muscular dystrophy (DMD) was hosted by the National Heart, Lung, and Blood Institute in collaboration with the Parent Project Muscular Dystrophy. An outcome of this meeting was to provide freely available detailed protocols for preclinical animal studies. The goal of these protocols is to improve the quality and reproducibility of cardiac preclinical studies aimed at developing new therapeutics for the prevention and treatment of DMD cardiomyopathy.

  17. Immune dysregulation may contribute to disease pathogenesis in spinal muscular atrophy mice

    PubMed Central

    Deguise, Marc-Olivier; De Repentigny, Yves; McFall, Emily; Auclair, Nicole; Sad, Subash

    2017-01-01

    Abstract Spinal muscular atrophy (SMA) has long been solely considered a neurodegenerative disorder. However, recent work has highlighted defects in many other cell types that could contribute to disease aetiology. Interestingly, the immune system has never been extensively studied in SMA. Defects in lymphoid organs could exacerbate disease progression by neuroinflammation or immunodeficiency. Smn depletion led to severe alterations in the thymus and spleen of two different mouse models of SMA. The spleen from Smn depleted mice was dramatically smaller at a very young age and its histological architecture was marked by mislocalization of immune cells in the Smn2B/- model mice. In comparison, the thymus was relatively spared in gross morphology but showed many histological alterations including cortex thinning in both mouse models at symptomatic ages. Thymocyte development was also impaired as evidenced by abnormal population frequencies in the Smn2B/- thymus. Cytokine profiling revealed major changes in different tissues of both mouse models. Consistent with our observations, we found that survival motor neuron (Smn) protein levels were relatively high in lymphoid organs compared to skeletal muscle and spinal cord during postnatal development in wild type mice. Genetic introduction of one copy of the human SMN2 transgene was enough to rescue splenic and thymic defects in Smn2B/- mice. Thus, Smn is required for the normal development of lymphoid organs, and altered immune function may contribute to SMA disease pathogenesis. PMID:28108555

  18. Elevated TGF β2 serum levels in Emery-Dreifuss muscular dystrophy: implications for myocyte and tenocyte differentiation and fibrogenic processes.

    PubMed

    Bernasconi, Pia; Carboni, Nicola; Ricci, Giulia; Siciliano, Gabriele; Politano, Luisa; Maggi, Lorenzo; Mongini, Tiziana; Vercelli, Liliana; Rodolico, Carmelo; Biagini, Elena; Boriani, Giuseppe; Ruggiero, Lucia; Santoro, Lucio; Schena, Elisa; Prencipe, Sabino; Evangelisti, Camilla; Pegoraro, Elena; Morandi, Lucia; Columbaro, Marta; Lanzuolo, Chiara; Sabatelli, Patrizia; Cavalcante, Paola; Cappelletti, Cristina; Bonne, Gisèle; Muchir, Antoine; Lattanzi, Giovanna

    2018-04-25

    Among rare diseases caused by mutations in LMNA gene, Emery-Dreifuss Muscular Dystrophy type 2 and Limb-Girdle muscular Dystrophy 1B are characterized by muscle weakness and wasting, joint contractures, cardiomyopathy with conduction system disorders. Circulating biomarkers for these pathologies have not been identified. Here, we analyzed the secretome of a cohort of patients affected by these muscular laminopathies in the attempt to identify a common signature. Multiplex cytokine assay showed that transforming growth factor beta 2 (TGF β2) and interleukin 17 serum levels are consistently elevated in the vast majority of examined patients, while interleukin 6 and basic fibroblast growth factor are altered in subgroups of patients. Levels of TGF β2 are also increased in fibroblast and myoblast cultures established from patient biopsies as well as in serum from mice bearing the H222P Lmna mutation causing Emery-Dreifuss muscular dystrophy in humans. Both patient serum and fibroblast conditioned media activated a TGF β2-dependent fibrogenic program in normal human myoblasts and tenocytes and inhibited myoblast differentiation. Consistent with these results, a TGF β2 neutralizing antibody avoided fibrogenic marker activation and myogenesis impairment. Cell intrinsic TGF β2-dependent mechanisms were also determined in laminopathic cells, where TGF β2 activated AKT/mTOR phosphorylation. These data show that TGF β2 contributes to the pathogenesis of Emery-Dreifuss Muscular Dystrophy type 2 and Limb-Girdle muscular Dystrophy 1B and can be considered a potential biomarker of those diseases. Further, the evidence of TGF β2 pathogenetic effects in tenocytes provides the first mechanistic insight into occurrence of joint contractures in muscular laminopathies.

  19. Weight, shape, and muscularity concerns in male and female adolescents: Predictors of change and influences on eating concern.

    PubMed

    Hoffmann, Svenja; Warschburger, Petra

    2017-02-01

    The purpose of this study was to examine the impact of age and weight status on adolescents' body dissatisfaction and its change over 20 months in a gender-comparing design. The influence of body image concern on eating concern was also investigated. In a prospective study, 675 male and female adolescents aged 12-16 were assessed using self-report questionnaires on weight, shape, muscularity, and eating concerns. Height and weight measurements were taken by trained personnel. Data were analyzed using structural equation modeling. Analyses of latent means revealed more pronounced weight/shape concern in females than males and more pronounced muscularity concern in males than females. Weight/shape concern increased in females over time, whereas muscularity concern remained stable in both genders. Baseline levels of weight/shape concern could be predicted by age and weight status in females and by weight status in males. The only predictor of change in weight/shape concern was weight status in males. Baseline levels of muscularity concern could be predicted by age in females and by weight status in males. Similar effects were found for changes in muscularity concern in both genders. Increases in weight/shape and muscularity concern were associated with more pronounced eating concern. The results confirm gender differences in distinctive facets of body image concern and its prediction. The relevance of increase in body image concern in adolescents is underlined by its association with eating concern in both genders. Further explanatory variables for change in body dissatisfaction should be examined in future studies. © 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2017; 50:139-147). © 2016 Wiley Periodicals, Inc.

  20. Early Detection of Myocardial Bioenergetic Deficits: A 9.4 Tesla Complete Non Invasive 31P MR Spectroscopy Study in Mice with Muscular Dystrophy.

    PubMed

    Cui, Weina; Jang, Albert; Zhang, Pengyuan; Thompson, Brian; Townsend, DeWayne; Metzger, Joseph M; Zhang, Jianyi

    2015-01-01

    Duchenne muscular dystrophy (DMD) is the most common fatal form of muscular dystrophy characterized by striated muscle wasting and dysfunction. Patients with DMD have a very high incidence of heart failure, which is increasingly the cause of death in DMD patients. We hypothesize that in the in vivo system, the dystrophic cardiac muscle displays bioenergetic deficits prior to any functional or structural deficits. To address this we developed a complete non invasive 31P magnetic resonance spectroscopy (31P MRS) approach to measure myocardial bioenergetics in the heart in vivo. Six control and nine mdx mice at 5 months of age were used for the study. A standard 3D -Image Selected In vivo Spectroscopy (3D-ISIS) sequence was used to provide complete gradient controlled three-dimensional localization for heart 31P MRS. These studies demonstrated dystrophic hearts have a significant reduction in PCr/ATP ratio compare to normal (1.59±0.13 vs 2.37±0.25, p<0.05). Our present study provides the direct evidence of significant cardiac bioenergetic deficits in the in vivo dystrophic mouse. These data suggest that energetic defects precede the development of significant hemodynamic or structural changes. The methods provide a clinically relevant approach to use myocardial energetics as an early marker of disease in the dystrophic heart. The new method in detecting the in vivo bioenergetics abnormality as an early non-invasive marker of emerging dystrophic cardiomyopathy is critical in management of patients with DMD, and optimized therapies aimed at slowing or reversing the cardiomyopathy.

  1. Exome sequencing identifies a DNAJB6 mutation in a family with dominantly-inherited limb-girdle muscular dystrophy.

    PubMed

    Couthouis, Julien; Raphael, Alya R; Siskind, Carly; Findlay, Andrew R; Buenrostro, Jason D; Greenleaf, William J; Vogel, Hannes; Day, John W; Flanigan, Kevin M; Gitler, Aaron D

    2014-05-01

    Limb-girdle muscular dystrophy primarily affects the muscles of the hips and shoulders (the "limb-girdle" muscles), although it is a heterogeneous disorder that can present with varying symptoms. There is currently no cure. We sought to identify the genetic basis of limb-girdle muscular dystrophy type 1 in an American family of Northern European descent using exome sequencing. Exome sequencing was performed on DNA samples from two affected siblings and one unaffected sibling and resulted in the identification of eleven candidate mutations that co-segregated with the disease. Notably, this list included a previously reported mutation in DNAJB6, p.Phe89Ile, which was recently identified as a cause of limb-girdle muscular dystrophy type 1D. Additional family members were Sanger sequenced and the mutation in DNAJB6 was only found in affected individuals. Subsequent haplotype analysis indicated that this DNAJB6 p.Phe89Ile mutation likely arose independently of the previously reported mutation. Since other published mutations are located close by in the G/F domain of DNAJB6, this suggests that the area may represent a mutational hotspot. Exome sequencing provided an unbiased and effective method for identifying the genetic etiology of limb-girdle muscular dystrophy type 1 in a previously genetically uncharacterized family. This work further confirms the causative role of DNAJB6 mutations in limb-girdle muscular dystrophy type 1D. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Gene expression in mdx mouse muscle in relation to age and exercise: aberrant mechanical-metabolic coupling and implications for pre-clinical studies in Duchenne muscular dystrophy.

    PubMed

    Camerino, Giulia Maria; Cannone, Maria; Giustino, Arcangela; Massari, Ada Maria; Capogrosso, Roberta Francesca; Cozzoli, Anna; De Luca, Annamaria

    2014-11-01

    Weakness and fatigability are typical features of Duchenne muscular dystrophy patients and are aggravated in dystrophic mdx mice by chronic treadmill exercise. Mechanical activity modulates gene expression and muscle plasticity. Here, we investigated the outcome of 4 (T4, 8 weeks of age) and 12 (T12, 16 weeks of age) weeks of either exercise or cage-based activity on a large set of genes in the gastrocnemius muscle of mdx and wild-type (WT) mice using quantitative real-time PCR. Basal expression of the exercise-sensitive genes peroxisome-proliferator receptor γ coactivator 1α (Pgc-1α) and Sirtuin1 (Sirt1) was higher in mdx versus WT mice at both ages. Exercise increased Pgc-1α expression in WT mice; Pgc-1α was downregulated by T12 exercise in mdx muscles, along with Sirt1, Pparγ and the autophagy marker Bnip3. Sixteen weeks old mdx mice showed a basal overexpression of the slow Mhc1 isoform and Serca2; T12 exercise fully contrasted this basal adaptation as well as the high expression of follistatin and myogenin. Conversely, T12 exercise was ineffective in WT mice. Damage-related genes such as gp91-phox (NADPH-oxidase2), Tgfβ, Tnfα and c-Src tyrosine kinase were overexpressed in mdx muscles and not affected by exercise. Likewise, the anti-inflammatory adiponectin was lower in T12-exercised mdx muscles. Chronic exercise with minor adaptive effects in WT muscles leads to maladaptation in mdx muscles with a disequilibrium between protective and damaging signals. Increased understanding of the pathways involved in the altered mechanical-metabolic coupling may help guide appropriate physical therapies while better addressing pharmacological interventions in translational research. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  3. Control of Abnormal Synchronization in Neurological Disorders

    PubMed Central

    Popovych, Oleksandr V.; Tass, Peter A.

    2014-01-01

    In the nervous system, synchronization processes play an important role, e.g., in the context of information processing and motor control. However, pathological, excessive synchronization may strongly impair brain function and is a hallmark of several neurological disorders. This focused review addresses the question of how an abnormal neuronal synchronization can specifically be counteracted by invasive and non-invasive brain stimulation as, for instance, by deep brain stimulation for the treatment of Parkinson’s disease, or by acoustic stimulation for the treatment of tinnitus. On the example of coordinated reset (CR) neuromodulation, we illustrate how insights into the dynamics of complex systems contribute to successful model-based approaches, which use methods from synergetics, non-linear dynamics, and statistical physics, for the development of novel therapies for normalization of brain function and synaptic connectivity. Based on the intrinsic multistability of the neuronal populations induced by spike timing-dependent plasticity (STDP), CR neuromodulation utilizes the mutual interdependence between synaptic connectivity and dynamics of the neuronal networks in order to restore more physiological patterns of connectivity via desynchronization of neuronal activity. The very goal is to shift the neuronal population by stimulation from an abnormally coupled and synchronized state to a desynchronized regime with normalized synaptic connectivity, which significantly outlasts the stimulation cessation, so that long-lasting therapeutic effects can be achieved. PMID:25566174

  4. Risk Factors for First Fractures Among Males With Duchenne or Becker Muscular Dystrophy.

    PubMed

    James, Katherine A; Cunniff, Christopher; Apkon, Susan D; Mathews, Katherine; Lu, Zhenqiang; Holtzer, Caleb; Pandya, Shree; Ciafaloni, Emma; Miller, Lisa

    2015-09-01

    Fractures are a significant concern for individuals with Duchenne/Becker muscular dystrophy with 21% to 44% of males experiencing a fracture. Factors that increase or decrease the risk for fracture have been suggested in past research, although statistical risk has not been determined. In this retrospective cohort study, we used the Muscular Dystrophy Surveillance, Tracking and Research Network cohort, a large, population-based sample to identify risk factors associated with first fractures in patients with Duchenne or Becker muscular dystrophy. Our study cohort included males with Duchenne or Becker muscular dystrophy born between 1982 and 2006 who resided in Arizona, Colorado, Georgia, Iowa, and Western New York, retrospectively identified and followed through 2010. We utilized a multivariate Cox proportional hazard model to determine hazard ratios for relevant factors associated with first fracture risk including race/ethnicity, surveillance site, ambulation status, calcium/vitamin D use and duration, bisphosphonate use and duration, and corticosteroid use and duration. Of 747 cases, 249 had at least 1 fracture (33.3%). Full-time wheelchair use increased the risk of first fracture by 75% for every 3 months of use (hazard ratio=1.75, 95% confidence interval, 1.14, 2.68), but corticosteroid use, bisphosphonate use, and calcium/vitamin D use did not significantly affect risk in the final adjusted model. In this cohort, first fractures were common and full-time wheelchair use, but not corticosteroid use, was identified as a risk factor. The impact of prevention measures should be more thoroughly assessed. Fractures are a significant concern for individuals with dystrophinopathies, but the contribution of various risk factors has not been consistently demonstrated.

  5. Altered movement patterns and muscular activity during single and double leg squats in individuals with anterior cruciate ligament injury.

    PubMed

    Trulsson, Anna; Miller, Michael; Hansson, Gert-Åke; Gummesson, Christina; Garwicz, Martin

    2015-02-13

    Individuals with Anterior Cruciate Ligament (ACL) injury often show altered movement patterns, suggested to be partly due to impaired sensorimotor control. Here, we therefore aimed to assess muscular activity during movements often used in ACL-rehabilitation and to characterize associations between deviations in muscular activity and specific altered movement patterns, using and further exploring the previously developed Test for substitution Patterns (TSP). Sixteen participants (10 women) with unilateral ACL rupture performed Single and Double Leg Squats (SLS; DLS). Altered movement patterns were scored according to TSP, and Surface Electromyography (SEMG) was recorded bilaterally in six hip, thigh and shank muscles. To quantify deviations in muscular activity, SEMG ratios were calculated between homonymous muscles on injured and non-injured sides, and between antagonistic muscles on the same side. Correlations between deviations of injured/non-injured side SEMG ratios and specific altered movement patterns were calculated. Injured/non-injured ratios were low at transition from knee flexion to extension in quadriceps in SLS, and in quadriceps and hamstrings in DLS. On injured side, the quadriceps/hamstrings ratio prior to the beginning of DLS and end of DLS and SLS, and tibialis/gastrocnemius ratio at end of DLS were lower than on non-injured side. Correlations were found between specific altered movement patterns and deviating muscular activity at transition from knee flexion to extension in SLS, indicating that the more deviating the muscular activity on injured side, the more pronounced the altered movement pattern. "Knee medial to supporting foot" correlated to lower injured/non-injured ratios in gluteus medius (rs = -0.73, p = 0.001), "lateral displacement of hip-pelvis-region" to lower injured/non-injured ratios in quadriceps (rs = -0.54, p = 0.03) and "displacement of trunk" to higher injured/non-injured ratios in gluteus medius (rs = 0.62, p = 0

  6. Isolation and characterization of mesoangioblasts from facioscapulohumeral muscular dystrophy muscle biopsies.

    PubMed

    Morosetti, Roberta; Mirabella, Massimiliano; Gliubizzi, Carla; Broccolini, Aldobrando; Sancricca, Cristina; Pescatori, Mario; Gidaro, Teresa; Tasca, Giorgio; Frusciante, Roberto; Tonali, Pietro Attilio; Cossu, Giulio; Ricci, Enzo

    2007-12-01

    Facioscapulohumeral muscular dystrophy (FSHD) is the third most frequent inherited muscle disease. Because in FSHD patients the coexistence of affected and unaffected muscles is common, myoblasts expanded from unaffected FSHD muscles have been proposed as suitable tools for autologous cell transplantation. Mesoangioblasts are a new class of adult stem cells of mesodermal origin, potentially useful for the treatment of primitive myopathies of different etiology. Here, we report the isolation and characterization of mesoangioblasts from FSHD muscle biopsies and describe morphology, proliferation, and differentiation abilities of both mesoangioblasts and myoblasts derived from various affected and unaffected muscles of nine representative FSHD patients. We demonstrate that mesoangioblasts can be efficiently isolated from FSHD muscle biopsies and expanded to an amount of cells necessary to transplant into an adult patient. Proliferating mesoangioblasts from all muscles examined did not differ from controls in terms of morphology, phenotype, proliferation rate, or clonogenicity. However, their differentiation ability into skeletal muscle was variably impaired, and this defect correlated with the overall disease severity and the degree of histopathologic abnormalities of the muscle of origin. A remarkable differentiation defect was observed in mesoangioblasts from all mildly to severely affected FSHD muscles, whereas mesoangioblasts from morphologically normal muscles showed no myogenic differentiation block. Our study could open the way to cell therapy for FSHD patients to limit muscle damage in vivo through the use of autologous mesoangioblasts capable of reaching damaged muscles and engrafting into them, without requiring immune suppression or genetic correction in vitro. Disclosure of potential conflicts of interest is found at the end of this article.

  7. A Role for Hypocretin/Orexin in Metabolic and Sleep Abnormalities in a Mouse Model of Non-metastatic Breast Cancer.

    PubMed

    Borniger, Jeremy C; Walker Ii, William H; Surbhi; Emmer, Kathryn M; Zhang, Ning; Zalenski, Abigail A; Muscarella, Stevie L; Fitzgerald, Julie A; Smith, Alexandra N; Braam, Cornelius J; TinKai, Tial; Magalang, Ulysses J; Lustberg, Maryam B; Nelson, Randy J; DeVries, A Courtney

    2018-05-14

    We investigated relationships among immune, metabolic, and sleep abnormalities in mice with non-metastatic mammary cancer. Tumor-bearing mice displayed interleukin-6 (IL-6)-mediated peripheral inflammation, coincident with altered hepatic glucose processing and sleep. Tumor-bearing mice were hyperphagic, had reduced serum leptin concentrations, and enhanced sensitivity to exogenous ghrelin. We tested whether these phenotypes were driven by inflammation using neutralizing monoclonal antibodies against IL-6; despite the reduction in IL-6 signaling, metabolic and sleep abnormalities persisted. We next investigated neural populations coupling metabolism and sleep, and observed altered activity within lateral-hypothalamic hypocretin/orexin (HO) neurons. We used a dual HO-receptor antagonist to test whether increased HO signaling was causing metabolic abnormalities. This approach rescued metabolic abnormalities and enhanced sleep quality in tumor-bearing mice. Peripheral sympathetic denervation prevented tumor-induced increases in serum glucose. Our results link metabolic and sleep abnormalities via the HO system, and provide evidence that central neuromodulators contribute to tumor-induced changes in metabolism. Copyright © 2018 Elsevier Inc. All rights reserved.

  8. Health services received by individuals with duchenne/becker muscular dystrophy.

    PubMed

    Pandya, Shree K; Campbell, Kim A; Andrews, Jennifer G; Meaney, F John; Ciafaloni, Emma

    2016-02-01

    Anecdotal reports from families and care providers suggest a wide variation in services received by individuals with Duchenne/Becker muscular dystrophy (DBMD). We documented the type and frequency of health services received by individuals with DBMD using the Muscular Dystrophy Surveillance Tracking and Research Network (MD STARnet) interview data released in June 2012. Interviews with eligible caregivers from 5 sites (Arizona, Colorado, Georgia, Iowa, and western New York) were conducted from April 2007 to March 2012. Two hundred ninety-six caregivers (66% of those contactable) participated in the interview. There were significant differences among sites in the specialists seen and services received. Concurrence with cardiac recommendations was higher than that with respiratory recommendations. The results of this survey support and quantify the anecdotal reports from families and care providers regarding the disparities in services received by individuals with DBMD. It remains to be determined whether these differences affect outcomes. © 2015 Wiley Periodicals, Inc.

  9. Prefrontal involvement related to cognitive impairment in progressive muscular atrophy.

    PubMed

    Raaphorst, Joost; van Tol, Marie-José; Groot, Paul F C; Altena, Ellemarije; van der Werf, Ysbrand D; Majoie, Charles B; van der Kooi, Anneke J; van den Berg, Leonard H; Schmand, Ben; de Visser, Marianne; Veltman, Dick J

    2014-08-26

    To examine brain activation patterns during verbal fluency performance in patients with progressive muscular atrophy (PMA) and amyotrophic lateral sclerosis (ALS). fMRI was used to examine the blood oxygen level-dependent response during letter and category fluency performance in 18 patients with PMA, 21 patients with ALS, and 17 healthy control subjects, matched for age and education. fMRI results are reported at p<0.05, family-wise error (FWE)-corrected for multiple comparisons. We analyzed effects of performance, age-related white matter changes (ARWMC), and regional brain volumes; all participants underwent neuropsychological investigation. Disease duration of patients with PMA (mean 26.0 months, SD 13.6) and ALS (22.2 months, SD 11.4) was comparable. Patients with PMA and ALS had mild to moderate disease severity and showed impaired letter fluency compared with controls. Between-group analysis showed a main effect of group in the left inferior frontal gyrus (IFG, Brodmann area 45) during letter fluency, which was unaffected by performance, ARWMC, and IFG volume: patients with PMA showed lower activation than controls but higher than that of patients with ALS (ALSabnormalities are related to an important clinical measure of executive dysfunction in patients with motor neuron disease with and without upper motor neuron signs. © 2014 American Academy of Neurology.

  10. Usefulness of sugammadex in a patient with Becker muscular dystrophy and dilated cardiomyopathy.

    PubMed

    Shimauchi, Tsukasa; Yamaura, Ken; Sugibe, Sayaka; Hoka, Sumio

    2014-09-01

    A 54-year-old patient with Becker muscular dystrophy and dilated cardiomyopathy underwent laparoscopic cholecystectomy under total intravenous anesthesia. Muscle relaxation was induced by rocuronium (0.4 mg/kg body weight) under train-of-four (TOF) ratio monitoring. The TOF ratio was 0 at intubation, and 0.2 at the end of surgery. Residual muscle relaxant activity was successfully reversed by sugammadex (2 mg/kg body weight) without any hemodynamic adverse effects (TOF ratio 1.0 at extubation). The clinical and hemodynamic findings suggest that sugammadex can be safely used in patients with Becker muscular dystrophy and dilated cardiomyopathy. Copyright © 2014. Published by Elsevier B.V.

  11. Impact of three genetic musculoskeletal diseases: a comparative synthesis of achondroplasia, Duchenne muscular dystrophy and osteogenesis imperfecta.

    PubMed

    Dogba, Maman Joyce; Rauch, Frank; Douglas, Erin; Bedos, Christophe

    2014-10-25

    Achondroplasia, Duchenne muscular dystrophy, and osteogenesis imperfecta are among the most frequent rare genetic disorders affecting the musculoskeletal system in children. Rare genetic disorders are severely disabling and can have substantial impacts on families, children, and on healthcare systems. This literature review aims to classify, summarize and compare these non-medical impacts of achondroplasia, Duchenne muscular dystrophy and osteogenesis imperfecta.

  12. Congenital abnormality of the vagina complicated by haemato-pyocolpos in a 1-year labrador retriever.

    PubMed

    Alonge, S; Romussi, S; Grieco, V; Luvoni, G C

    2015-06-01

    A 1-year-old female Labrador retriever was referred with a few days history of haematic-like vulvar discharge. Physical examination, vaginal inspection and palpation did not reveal any remarkable finding. Transabdominal ultrasound showed echogenic fluid accumulation in the vagina suggesting haemato-pyocolpos. An exploratory laparotomy was performed: a well-delimited ectasic vagina was identified. Ovariohysterectomy and partial vaginectomy and vaginoplasty were performed to spay the bitch and to remove the ectasic vagina. Post-operative recovery and 12-month follow-up were uneventful. Clinical, morphological and histological findings were consistent with a congenital abnormality of the muscular layer of the vagina complicated by haemato-pyocolpos. The disorganization of the vaginal tunica muscularis may have acted as locus minoris resistentiae in the vaginal wall. The organ was dilated and atonic due to the gradual accumulation of physiological fluids complicated by an overgrowth of genital bacteria. This congenital disorder has to be taken into account as differential diagnosis of haemato-pyocolpos with vaginal discharge in young bitches. © 2015 Blackwell Verlag GmbH.

  13. Familial hyperinsulinemia associated with secretion of an abnormal insulin, and coexistence of insulin resistance in the propositus.

    PubMed

    Vinik, A I; Seino, S; Funakoshi, A; Schwartz, J; Matsumoto, M; Schteingart, D E; Fu, Z Z; Tsai, S T

    1986-04-01

    A 45-yr-old muscular nonobese white man who had a 9-yr history of syncopal episodes was studied on several occasions between April 1979 and August 1984. Fasting glucose concentrations ranged between 74-115 mg/dl, and those of insulin ranged between 14-64 microU/ml. Reactive hypoglycemia 3-4 h after ingestion of glucose occurred in the first 2 yr. Glucose tolerance was impaired in 1979, from February 1982 through September 1983, and again in August 1984. The maximum plasma insulin response to glucose ranged between 475-1630 microU/ml. When studied in November 1982, insulin (0.1 U/kg) caused a fall in blood glucose concentration of only 25% (normal, greater than 50%), and maximal glucose utilization during the euglycemic hyperinsulinemic clamp was 7.5 mg/kg . min (normal, greater than 12 mg/kg . min). Plasma counterregulatory hormone concentrations were normal, and antibodies to insulin and the insulin receptor were absent. Binding of exogenous insulin to the patient's cellular receptors (monocytes, red blood cells, and skin fibroblasts) was normal. Insulin was purified from plasma by immunoaffinity and molecular sieve chromatography and was found to elute later than human insulin on reversed phase high performance liquid chromatography. It was more hydrophobic than normal human insulin and had only 10% of the activity of normal insulin in terms of ability to bind to and stimulate glucose metabolism in isolated rat adipocytes. The abnormal insulin was identified in two of three sons and a sister, but not in the mother, brother, or niece. Sensitivity to insulin was normal in the two sons who had abnormal insulin. These results suggest that in this family the abnormal insulin was due to a biosynthetic defect, inherited as an autosomal dominant trait. The hyperinsulinemia was not associated with diabetes in family members who had no insulin resistance.

  14. Characteristic analysis of the lower limb muscular strength training system applied with MR dampers.

    PubMed

    Yu, Chang Ho; Piao, Young Jun; Kim, Kyung; Kwon, Tae Kyu

    2014-01-01

    A new training system that can adjust training intensity and indicate the center pressure of a subject was proposed by applying controlled electric current to the Magneto-Rheological damper. The experimental studying on the muscular activities were performed in lower extremities during maintaining and moving exercises, which were processed on an unstable platform with Magneto rheological dampers and recorded in a monitor. The electromyography (EMG) signals of the eight muscles in lower extremities were recorded and analyzed in certain time and frequency domain. Muscles researched in this paper were rectus femoris (RF), biceps femoris (BF), tensor fasciae latae (TFL), vastuslateralis (VL), vastusmedialis (VM), gastrocnemius (Ga), tibialis anterior (TA), and soleus (So). Differences of muscular activities during four moving exercises were studied in our experimental results. The rate of the increment of the muscular activities was affected by the condition of the unstable platform with MR dampers, which suggested the difference of moving exercises could selectively train each muscle with varying intensities. Furthermore, these findings also proposed that this training system can improve the ability of postural balance.

  15. Diffusion and ideal MRI techniques to characterize limb-girdle muscular dystrophy

    NASA Astrophysics Data System (ADS)

    Hernández-Salazar, G.; Hidalgo-Tobon, S.; Vargas-Cañas, S.; Marrufo-Melendez, O.; Solis-Najera, S.; Taboada-Barajas, J.; Rodríguez, A. O.; Delgado-Hernández, R.

    2012-10-01

    Limb-girdle muscular dystrophies (LGMD) are a group of autosomal dominantly or recessively inherited muscular dystrophies that also present with primary proximal (limb-girdle) muscle weakness. In the thigh, muscles at the back are affected, with a tendency to preserve the tibialis anterior and gastrocnemius. The aim of this study was to compare quantitative MRI measurements from IDEAL-based imaging and DW imaging in the thigh muscles of adults with LGMDs and healthy volunteers(HC). Six women (three patients and three healthy volunteers) were examined. Imaging experiments were conducted on a 1.5T GE scanner (General Electric Medical Systems. Milwaukee). T1 IDEAL 2D images and diffusion images were acquired. Results demonstrated that the use of noninvasive MRI techniques may provide the means to characterize the muscle through quantitative methods to determine the percentage of fat and ADC values.

  16. Expression of the Murine Duchenne Muscular Dystrophy Gene in Muscle and Brain

    NASA Astrophysics Data System (ADS)

    Chamberlain, Jeffrey S.; Pearlman, Joel A.; Muzny, Donna M.; Gibbs, Richard A.; Ranier, Joel E.; Reeves, Alice A.; Caskey, C. Thomas

    1988-03-01

    Complementary DNA clones were isolated that represent the 5' terminal 2.5 kilobases of the murine Duchenne muscular dystrophy (Dmd) messenger RNA (mRNA). Mouse Dmd mRNA was detectable in skeletal and cardiac muscle and at a level approximately 90 percent lower in brain. Dmd mRNA is also present, but at much lower than normal levels, in both the muscle and brain of three different strains of dystrophic mdx mice. The identification of Dmd mRNA in brain raises the possibility of a relation between human Duchenne muscular dystrophy (DMD) gene expression and the mental retardation found in some DMD males. These results also provide evidence that the mdx mutations are allelic variants of mouse Dmd gene mutations.

  17. Examination of a muscular activity estimation model using a Bayesian network for the influence of an ankle foot orthosis.

    PubMed

    Inoue, Jun; Kawamura, Kazuya; Fujie, Masakatsu G

    2012-01-01

    In the present paper, we examine the appropriateness of a new model to examine the activity of the foot in gait. We developed an estimation model for foot-ankle muscular activity in the design of an ankle-foot orthosis by means of a statistical method. We chose three muscles for measuring muscular activity and built a Bayesian network model to confirm the appropriateness of the estimation model. We experimentally examined the normal gait of a non-disabled subject. We measured the muscular activity of the lower foot muscles using electromyography, the joint angles, and the pressure on each part of the sole. From these data, we obtained the causal relationship at every 10% level for these factors and built models for the stance phase, control term, and propulsive term. Our model has three advantages. First, it can express the influences that change during gait because we use 10% level nodes for each factor. Second, it can express the influences of factors that differ for low and high muscular-activity levels. Third, we created divided models that are able to reflect the actual features of gait. In evaluating the new model, we confirmed it is able to estimate all muscular activity level with an accuracy of over 90%.

  18. Structure and postembryonic development of the intersegmental nodules in the non-muscular joints of the antennae in Rhodnius prolixus.

    PubMed

    Ospina-Rozo, Bibiana; Forero-Shelton, Manu; Molina, Jorge

    2017-03-01

    The antennae of Insecta consist of two basal segments and the distal annulated flagellum lacking intrinsic muscles. Non-muscular joints are important to preserve the flexibility and structure of the long heteropteran antennae which bear an intersegmental nodule on each non-muscular joint. Little is known about their properties or function. Here we characterize the structure and postembryonic development of the non-muscular joints of Rhodnius prolixus antennae. Using Scanning Electron Microscopy, we tracked the changes in shape and size of both intersegmental nodules during the course of the hemimetabolous insect life cycle. Using Atomic Force Microscopy, we established a qualitative correlation between the topography of the surface and the rigidity of the joint between pedicel and flagellum. Our results confirmed the presence of two sub-articulations on each non-muscular joint. Also, the two intersegmental nodules have different origins: the one between the two flagellar segments (intraflagelloid) is a sclerite already present from the early nymph, while the nodule between pedicel and flagellum (prebasiflagellite) originates by gradual separation of the proximal end of the basiflagellum during postembryonic development. Various changes occur in the non-muscular joints and segments of the antenna during the life cycle of R. prolixus. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Reassessing the improbability of a muscular crinoid stem

    NASA Astrophysics Data System (ADS)

    Gorzelak, Przemysław; Głuchowski, Edward; Salamon, Mariusz A.

    2014-08-01

    Muscular articulations in modern stalked crinoids are only present in the arms. Although it has been suggested that certain coiled-stemmed fossil taxa may have been functionally adapted to utilize muscles, evidence supporting this interpretation is lacking. Here, we use cathodoluminescence and SEM to reveal the skeletal microstructure of the enigmatic coiled-stemmed taxon Ammonicrinus (Flexibilia). Based on the well-established link between skeletal microstructure and the nature of infilling soft tissues in modern echinoderms, we reconstructed the palaeoanatomy of the Middle Devonian ammonicrinids. We show that their median columnals with elongated lateral columnal enclosure extensions (LCEE) have stereom microstructure unexpectedly resembling that in the crinoid muscular arm plates. In particular, large ligamentary facets, that are present on each side of a transverse ridge, are mainly comprised of fine galleried stereom that is indicative of the mutable collagenous tissues. In contrast, fine labyrinthic stereom, commonly associated with muscles, is situated in the periphery on each side of the surface of elongated LCEE. Our findings thus strongly suggest that the muscles may have also been present in the stem of ammonicrinids. These results reassess the previous hypotheses about evolution of muscles in crinoids and provide new insights into the mode of life of Ammonicrinus.

  20. Reassessing the improbability of a muscular crinoid stem

    PubMed Central

    Gorzelak, Przemysław; Głuchowski, Edward; Salamon, Mariusz A.

    2014-01-01

    Muscular articulations in modern stalked crinoids are only present in the arms. Although it has been suggested that certain coiled-stemmed fossil taxa may have been functionally adapted to utilize muscles, evidence supporting this interpretation is lacking. Here, we use cathodoluminescence and SEM to reveal the skeletal microstructure of the enigmatic coiled-stemmed taxon Ammonicrinus (Flexibilia). Based on the well-established link between skeletal microstructure and the nature of infilling soft tissues in modern echinoderms, we reconstructed the palaeoanatomy of the Middle Devonian ammonicrinids. We show that their median columnals with elongated lateral columnal enclosure extensions (LCEE) have stereom microstructure unexpectedly resembling that in the crinoid muscular arm plates. In particular, large ligamentary facets, that are present on each side of a transverse ridge, are mainly comprised of fine galleried stereom that is indicative of the mutable collagenous tissues. In contrast, fine labyrinthic stereom, commonly associated with muscles, is situated in the periphery on each side of the surface of elongated LCEE. Our findings thus strongly suggest that the muscles may have also been present in the stem of ammonicrinids. These results reassess the previous hypotheses about evolution of muscles in crinoids and provide new insights into the mode of life of Ammonicrinus. PMID:25116414

  1. Assessment of 28 trace elements and 17 amino acid levels in muscular tissues of broiler chicken (Gallus gallus) suffering from arsenic trioxide.

    PubMed

    Li, Si-Wen; He, Ying; Zhao, Hong-Jing; Wang, Yu; Liu, Juan-Juan; Shao, Yi-Zhi; Li, Jing-Lun; Sun, Xiao; Zhang, Li-Na; Xing, Ming-Wei

    2017-10-01

    The contents of 28 trace elements, 17 amino acid were evaluated in muscular tissues (wings, crureus and pectoralis) of chickens in response to arsenic trioxide (As 2 O 3 ). A total of 200 one-day-old male Hy-line chickens were fed either a commercial diet (C-group) or an As 2 O 3 supplement diet containing 7.5mg/kg (L-group), 15mg/kg (M-group) or 30mg/kg (H-group) As 2 O 3 for 90 days. The elements content was analyzed by inductively coupled plasma mass spectrometry (ICP-MS). Under As 2 O 3 exposure, the concentration of As were elevated 8.87-15.76 fold, 7.93-15.63 fold and 5.94-12.45 fold in wings, crureus and pectoralis compared to the corresponding C-group, respectively. 19 element levels (lithium (Li), magnesium (Mg), aluminum (Al), silicon (Si), kalium (K), vanadium (V), chromium (Cr), manganese (Mn), nickel (Ni), copper (Cu), selenium (Se), strontium (Sr), molybdenum (Mo), cadmium (Cd), tin (Sn), antimony (Sb), barium (Ba), mercury (Hg) and lead (Pb), 9 element levels (K, Co, Ni, Cu, As, Se, Sr, Sn, Ba and Hg) and 4 element levels (Mn, cobalt (Co), As, Sr and Ba) were significantly increased (P < 0.05) in wing, crureus and pectoralis, respectively. 2 element levels (sodium (Na) and zinc (Zn)), 5 element levels (Li, Na, Si, titanium (Ti and Cr), 13 element levels (Li, Na, Mg, K, V, Cr, iron (Fe), Cu, Zn, Mo, Sn, Hg and Pb) were significantly decreased (P < 0.05) in wing muscle, crureus and pectoralis, respectively. Additionally, in crureus and pectoralis, the content of total amino acids (TAA) was no significant alterations in L and M-group and then increased approximately 10.2% and 7.6% in H-group, respectively (P < 0.05). In wings, the level of total amino acids increased approximately 10% in L-group, whereas it showed unchanged in M and H-group compared to the corresponding C-group. We also observed that significantly increased levels of proline, cysteine, aspartic acid, methionine along with decrease in the tyrosine levels in muscular tissues compared to

  2. Gene Expression Profiling in Limb-Girdle Muscular Dystrophy 2A

    PubMed Central

    Sáenz, Amets; Azpitarte, Margarita; Armañanzas, Rubén; Leturcq, France; Alzualde, Ainhoa; Inza, Iñaki; García-Bragado, Federico; De la Herran, Gaspar; Corcuera, Julián; Cabello, Ana; Navarro, Carmen; De la Torre, Carolina; Gallardo, Eduard; Illa, Isabel; de Munain, Adolfo López

    2008-01-01

    Limb-girdle muscular dystrophy type 2A (LGMD2A) is a recessive genetic disorder caused by mutations in calpain 3 (CAPN3). Calpain 3 plays different roles in muscular cells, but little is known about its functions or in vivo substrates. The aim of this study was to identify the genes showing an altered expression in LGMD2A patients and the possible pathways they are implicated in. Ten muscle samples from LGMD2A patients with in which molecular diagnosis was ascertained were investigated using array technology to analyze gene expression profiling as compared to ten normal muscle samples. Upregulated genes were mostly those related to extracellular matrix (different collagens), cell adhesion (fibronectin), muscle development (myosins and melusin) and signal transduction. It is therefore suggested that different proteins located or participating in the costameric region are implicated in processes regulated by calpain 3 during skeletal muscle development. Genes participating in the ubiquitin proteasome degradation pathway were found to be deregulated in LGMD2A patients, suggesting that regulation of this pathway may be under the control of calpain 3 activity. As frizzled-related protein (FRZB) is upregulated in LGMD2A muscle samples, it could be hypothesized that β-catenin regulation is also altered at the Wnt signaling pathway, leading to an incorrect myogenesis. Conversely, expression of most transcription factor genes was downregulated (MYC, FOS and EGR1). Finally, the upregulation of IL-32 and immunoglobulin genes may induce the eosinophil chemoattraction explaining the inflammatory findings observed in presymptomatic stages. The obtained results try to shed some light on identification of novel therapeutic targets for limb-girdle muscular dystrophies. PMID:19015733

  3. Tracking the Development of Muscular Myoglobin Stores in Mysticete Calves

    PubMed Central

    Cartwright, Rachel; Newton, Cori; West, Kristi M.; Rice, Jim; Niemeyer, Misty; Burek, Kathryn; Wilson, Andrew; Wall, Alison N.; Remonida-Bennett, Jean; Tejeda, Areli; Messi, Sarah; Marcial-Hernandez, Lila

    2016-01-01

    For marine mammals, the ability to tolerate apnea and make extended dives is a defining adaptive trait, facilitating the exploitation of marine food resources. Elevated levels of myoglobin within the muscles are a consistent hallmark of this trait, allowing oxygen collected at the surface to be stored in the muscles and subsequently used to support extended dives. In mysticetes, the largest of marine predators, details on muscular myoglobin levels are limited. The developmental trajectory of muscular myoglobin stores has yet to be documented and any physiological links between early behavior and the development of muscular myoglobin stores remain unknown. In this study, we used muscle tissue samples from stranded mysticetes to investigate these issues. Samples from three different age cohorts and three species of mysticetes were included (total sample size = 18). Results indicate that in mysticete calves, muscle myoglobin stores comprise only a small percentage (17–23%) of conspecific adult myoglobin complements. Development of elevated myoglobin levels is protracted over the course of extended maturation in mysticetes. Additionally, comparisons of myoglobin levels between and within muscles, along with details of interspecific differences in rates of accumulation of myoglobin in very young mysticetes, suggest that levels of exercise may influence the rate of development of myoglobin stores in young mysticetes. This new information infers a close interplay between the physiology, ontogeny and early life history of young mysticetes and provides new insight into the pressures that may shape adaptive strategies in migratory mysticetes. Furthermore, the study highlights the vulnerability of specific age cohorts to impending changes in the availability of foraging habitat and marine resources. PMID:26788728

  4. Relationship between cardiopulmonary responses and isokinetic moments: the optimal angular velocity for muscular endurance

    PubMed Central

    Lee, Chan-Bok; Eun, Denny; Kim, Kang-Ho; Park, Jae-Wan; Jee, Yong-Seok

    2017-01-01

    Most protocols for testing and rehabilitation for recovery and improvement of muscular endurance have been set at 180°/sec, 240°/sec, and 300°/sec. These protocols can cause confusion to clinical providers or other researchers. This study was aimed at investigating the optimal isokinetic angular speed for measuring or developing muscular endurance after assessing the relationship between cardiopulmonary responses and isokinetic moments. This study was conducted with 31 male and female college students. Graded exercise test and body composition were measured as well as the isokinetic moments of the knee muscles at three angular speeds: 180°/sec, 240°/sec, and 300°/sec. The specific isokinetic moments of knee muscles that were measured included: peak torque (PT) and total work (TW) on extensor (e) and flexor (f) of knee joints, which were denoted as ePT180, fPT180, eTW180, fTW180, ePT240, fPT240, eTW240, fTW240, ePT300, fPT300, eTW300, and fTW300 according to the three angular speeds. Spearman correlation test was used to examine the relationship between the sum means of cardiopulmonary responses and the variables of isokinetic moments. This study confirmed that the optimal angular speed for testing or training for muscular endurance was 180°/sec, which showed a stronger relationship between cardiopulmonary responses and isokinetic moments. Therefore, this angular speed is recommended for testing and training for muscular endurance of the knee joints. PMID:28503531

  5. Somatropin treatment of spinal muscular atrophy: a placebo-controlled, double-blind crossover pilot study.

    PubMed

    Kirschner, J; Schorling, D; Hauschke, D; Rensing-Zimmermann, C; Wein, U; Grieben, U; Schottmann, G; Schara, U; Konrad, K; Müller-Felber, W; Thiele, S; Wilichowski, E; Hobbiebrunken, E; Stettner, G M; Korinthenberg, R

    2014-02-01

    In preclinical studies growth hormone and its primary mediator IGF-1 have shown potential to increase muscle mass and strength. A single patient with spinal muscular atrophy reported benefit after compassionate use of growth hormone. Therefore we evaluated the efficacy and safety of growth hormone treatment for spinal muscular atrophy in a multicenter, randomised, double-blind, placebo-controlled, crossover pilot trial. Patients (n = 19) with type II/III spinal muscular atrophy were randomised to receive either somatropin (0.03 mg/kg/day) or placebo subcutaneously for 3 months, followed by a 2-month wash-out phase before 3 months of treatment with the contrary remedy. Changes in upper limb muscle strength (megascore for elbow flexion and hand-grip in Newton) were assessed by hand-held myometry as the primary measure of outcome. Secondary outcome measures included lower limb muscle strength, motor function using the Hammersmith Functional Motor Scale and other functional tests for motor function and pulmonary function. Somatropin treatment did not significantly affect upper limb muscle strength (point estimate mean: 0.08 N, 95% confidence interval (CI:-3.79;3.95, p = 0.965), lower limb muscle strength (point estimate mean: 2.23 N, CI:-2.19;6.63, p = 0.302) or muscle and pulmonary function. Side effects occurring during somatropin treatment corresponded with well-known side effects of growth hormone substitution in patients with growth hormone deficiency. In this pilot study, growth hormone treatment did not improve muscle strength or function in patients with spinal muscular atrophy type II/III. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. Relationship between cardiopulmonary responses and isokinetic moments: the optimal angular velocity for muscular endurance.

    PubMed

    Lee, Chan-Bok; Eun, Denny; Kim, Kang-Ho; Park, Jae-Wan; Jee, Yong-Seok

    2017-04-01

    Most protocols for testing and rehabilitation for recovery and improvement of muscular endurance have been set at 180°/sec, 240°/sec, and 300°/sec. These protocols can cause confusion to clinical providers or other researchers. This study was aimed at investigating the optimal isokinetic angular speed for measuring or developing muscular endurance after assessing the relationship between cardiopulmonary responses and isokinetic moments. This study was conducted with 31 male and female college students. Graded exercise test and body composition were measured as well as the isokinetic moments of the knee muscles at three angular speeds: 180°/sec, 240°/sec, and 300°/sec. The specific isokinetic moments of knee muscles that were measured included: peak torque (PT) and total work (TW) on extensor (e) and flexor (f) of knee joints, which were denoted as ePT180, fPT180, eTW180, fTW180, ePT240, fPT240, eTW240, fTW240, ePT300, fPT300, eTW300, and fTW300 according to the three angular speeds. Spearman correlation test was used to examine the relationship between the sum means of cardiopulmonary responses and the variables of isokinetic moments. This study confirmed that the optimal angular speed for testing or training for muscular endurance was 180°/sec, which showed a stronger relationship between cardiopulmonary responses and isokinetic moments. Therefore, this angular speed is recommended for testing and training for muscular endurance of the knee joints.

  7. Recurrent Fat Embolic Strokes in a Patient With Duchenne Muscular Dystrophy With Long Bone Fractures and a Patent Foramen Ovale.

    PubMed

    Bugnitz, Christopher J; Cripe, Linda H; Lo, Warren D; Flanigan, Kevin M

    2016-10-01

    Individuals with Duchenne muscular dystrophy have an increased risk of long bone fractures. Such fractures are sometimes associated with brain dysfunction due to fat embolism syndrome, although this syndrome has seldom been documented in muscular dystrophy patients. We describe a child with Duchenne muscular dystrophy who developed fat embolism syndrome with neurological dysfunction following multiple long bone fractures. He experienced recurrent cerebral infarctions that probably resulted from embolization through a patent foramen ovale. The patent foramen ovale was closed by an occluder device in the cardiac catheterization laboratory, and he did not experience further infarctions. Fat embolism with ischemic cerebral infarction can occur in individuals with Duchenne muscular dystrophy following long bone fractures. In this setting it is important to identify and close atrial level shunts in order to prevent additional infarctions. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Perceived social pressures and the internalization of the mesomorphic ideal: The role of drive for muscularity and autonomy in physically active men.

    PubMed

    Edwards, Christian; Tod, David; Molnar, Gyozo; Markland, David

    2016-03-01

    We examined if there were both direct and indirect relationships (via the drive for muscularity) between the perceived pressure to be muscular and internalization of the mesomorphic ideal, and if autonomy moderates these relationships in physically active men. A sample of 330 men, who were undergraduate students studying sport, completed the Behavioral Regulation in Exercise Questionnaire-2, the Mesomorphic Ideal Internalization subscale of the revised male version Sociocultural Attitudes Toward Appearance Questionnaire, the Perceived Sociocultural Pressure Scale-Modified, and the Drive for Muscularity Scale Attitudes subscale. Perceived pressure predicted internalization directly, and indirectly through the drive for muscularity. The direct relationship between pressure and internalization was weaker under higher levels of autonomy. The indirect path, via drive for muscularity, was stronger under higher levels of autonomy. These results provide insights into why men vary in the degree to which they internalize pressure to develop a mesomorphic ideal, supporting further examination of autonomy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Dysferlin, annexin A1, and mitsugumin 53 are upregulated in muscular dystrophy and localize to longitudinal tubules of the T-system with stretch.

    PubMed

    Waddell, Leigh B; Lemckert, Frances A; Zheng, Xi F; Tran, Jenny; Evesson, Frances J; Hawkes, Joanne M; Lek, Angela; Street, Neil E; Lin, Peihui; Clarke, Nigel F; Landstrom, Andrew P; Ackerman, Michael J; Weisleder, Noah; Ma, Jianjie; North, Kathryn N; Cooper, Sandra T

    2011-04-01

    Mutations in dysferlin cause an inherited muscular dystrophy because of defective membrane repair. Three interacting partners of dysferlin are also implicated in membrane resealing: caveolin-3 (in limb girdle muscular dystrophy type 1C), annexin A1, and the newly identified protein mitsugumin 53 (MG53). Mitsugumin 53 accumulates at sites of membrane damage, and MG53-knockout mice display a progressive muscular dystrophy. This study explored the expression and localization of MG53 in human skeletal muscle, how membrane repair proteins are modulated in various forms of muscular dystrophy, and whether MG53 is a primary cause of human muscle disease. Mitsugumin 53 showed variable sarcolemmal and/or cytoplasmic immunolabeling in control human muscle and elevated levels in dystrophic patients. No pathogenic MG53 mutations were identified in 50 muscular dystrophy patients, suggesting that MG53 is unlikely to be a common cause of muscular dystrophy in Australia. Western blot analysis confirmed upregulation of MG53, as well as of dysferlin, annexin A1, and caveolin-3 to different degrees, in different muscular dystrophies. Importantly, MG53, annexin A1, and dysferlin localize to the t-tubule network and show enriched labeling at longitudinal tubules of the t-system in overstretch. Our results suggest that longitudinal tubules of the t-system may represent sites of physiological membrane damage targeted by this membrane repair complex.

  10. Electrocardiographic abnormalities in opiate addicts.

    PubMed

    Wallner, Christina; Stöllberger, Claudia; Hlavin, Anton; Finsterer, Josef; Hager, Isabella; Hermann, Peter

    2008-12-01

    To determine in a cross-sectional study the prevalence of electrocardiographic (ECG) abnormalities in opiate addicts who were therapy-seeking and its association with demographic, clinical and drug-specific parameters. In consecutive therapy-seeking opiate addicts, a 12-lead ECG was registered within 24 hours after admission and evaluated according to a pre-set protocol between October 2004 and August 2006. Additionally, demographic, clinical and drug-specific parameters were recorded. Included were 511 opiate-addicts, 25% female, with a mean age of 29 years (range 17-59 years). One or more ECG abnormalities were found in 314 patients (61%). In the 511 patients we found most commonly ST abnormalities (19%), QTc prolongation (13%), tall R- and/or S-waves (11%) and missing R progression (10%). ECG abnormalities were more common in males than in females (64 versus 54%, P < 0.05), and in patients with positive than negative urine findings for cannabis (68 versus 57%, P < 0.05). Patients with ST abnormalities were more often males than females (21 versus 11%, P < 0.05), had a history of seizures less often (16 versus 27%, P < 0.05), had positive than negative urine findings for cannabis more often (26 versus 15%, P < 0.01) and had negative than positive urine findings for methadone more often (21 versus 11%, P < 0.05). QTc prolongation was more frequent in patients with high dosages of maintenance drugs than in patients with medium or low dosages (27 versus 12 versus 10%, P < 0.05) and in patients whose urine findings were positive than negative for methadone (23 versus 11%, P < 0.001) as well as for benzodiazepines (17 versus 9%, P < 0.05). Limitations of the data are that in most cases other risk factors for the cardiac abnormalities were not known. ECG abnormalities are frequent in opiate addicts. The most frequent ECG abnormalities are ST abnormalities, QTc prolongation and tall R- and/or S-waves. ST abnormalities are associated with cannabis, and QTc prolongation

  11. Dropped head congenital muscular dystrophy caused by de novo mutations in LMNA.

    PubMed

    Karaoglu, Pakize; Quizon, Nicolas; Pergande, Matthias; Wang, Haicui; Polat, Ayşe Ipek; Ersen, Ayca; Özer, Erdener; Willkomm, Lena; Hiz Kurul, Semra; Heredia, Raúl; Yis, Uluç; Selcen, Duygu; Çirak, Sebahattin

    2017-04-01

    Dropped head syndrome is an easily recognizable clinical presentation of Lamin A/C-related congenital muscular dystrophy. Patients usually present in the first year of life with profound neck muscle weakness, dropped head, and elevated serum creatine kinase. Two patients exhibited head drop during infancy although they were able to sit independently. Later they developed progressive axial and limb-girdle weakness. Creatine kinase levels were elevated and muscle biopsies of both patients showed severe dystrophic changes. The distinctive clinical hallmark of the dropped head led us to the diagnosis of Lamin A/C-related congenital muscular dystrophy, with a pathogenic de novo mutation p.Glu31del in the head domain of the Lamin A/C gene in both patients. Remarkably, one patient also had a central involvement with white matter changes on brain magnetic resonance imaging. Lamin A/C-related dropped-head syndrome is a rapidly progressive congenital muscular dystrophy and may lead to loss of ambulation, respiratory insufficiency, and cardiac complications. Thus, the genetic diagnosis of dropped-head syndrome as L-CMD and the implicated clinical care protocols are of vital importance for these patients. This disease may be underdiagnosed, as only a few genetically confirmed cases have been reported. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  12. [Pathomechanism and therapeutic strategy of Fukuyama congenital muscular dystrophy and related disorders].

    PubMed

    Toda, Tatsushi

    2009-11-01

    Hypoglycosylation and reduced laminin-binding activity of alpha-dystroglycan are common characteristics of dystroglycanopathy, which is a group of congenital and limb-girdle muscular dystrophies. We previously identified the genes for Fukuyama congenital muscular dystrophy (FCMD) and muscle-eye-brain disease (MEB). FCMD, caused by a mutation in the fukutin gene, is a severe form of dystroglycanopathy. Knock-in mice carrying the founder retrotransposal insertion exhibited hypoglycosylated alpha-dystroglycan; however, no signs of muscular dystrophy were observed. More sensitive methods detected minor levels of intact alpha-dystroglycan, and solid-phase assays determined laminin binding levels to be approximately 50% of normal. In contrast, intact alpha-dystroglycan is undetectable in the dystrophic Large mouse, and laminin-binding activity is markedly reduced. These data indicate that a small amount of intact alpha-dystroglycan is sufficient to maintain muscle cell integrity in knock-in mice, suggesting that the treatment of dystroglycanopathies might not require the full recovery of glycosylation. Transfer of fukutin into knock-in mice restored glycosylation of alpha-dystroglycan. Transfer of LARGE produced laminin-binding forms of alpha-dystroglycan in both knock-in mice and the POMGnT1 mutant mouse. These data suggest that even partial restoration of alpha-dystroglycan glycosylation and laminin-binding activity by replacing or augmenting glycosylation-related genes might effectively deter dystroglycanopathy progression and thus provide therapeutic benefits.

  13. Poor Facial Affect Recognition among Boys with Duchenne Muscular Dystrophy

    ERIC Educational Resources Information Center

    Hinton, V. J.; Fee, R. J.; De Vivo, D. C.; Goldstein, E.

    2007-01-01

    Children with Duchenne or Becker muscular dystrophy (MD) have delayed language and poor social skills and some meet criteria for Pervasive Developmental Disorder, yet they are identified by molecular, rather than behavioral, characteristics. To determine whether comprehension of facial affect is compromised in boys with MD, children were given a…

  14. Reconstructing the muscular ground pattern of phylactolaemate bryozoans: first data from gelatinous representatives.

    PubMed

    Gawin, Natalie; Wanninger, Andreas; Schwaha, Thomas

    2017-11-07

    Phylactolaemata is commonly regarded the earliest branch within Bryozoa and thus the sister group to the other bryozoan taxa, Cyclostomata and Gymnolaemata. Therefore, the taxon is important for the reconstruction of the bryozoan morphological ground pattern. In this study the myoanatomy of Pectinatella magnifica, Cristatella mucedo and Hyalinella punctata was analysed by means of histology, f-actin staining and confocal laser-scanning microscopy in order to fill gaps in knowledge concerning the myoanatomy of Phylactolaemata. The retractor muscles and muscles of the aperture, gut, body wall, tentacle sheath, lophophore constitute the most prominent muscular subsets in these species. The lophophore shows longitudinal muscle bands in the tentacles, lophophoral arm muscles, epistome musculature and hitherto undescribed muscles of the ring canal. In general the muscular system of the three species is very similar with differences mainly in the body wall, tentacle sheath and epistome. The body wall contains an orthogonal grid of musculature. The epistome exhibits either a muscular meshwork in the epistomal wall or muscle fibers traversing the epistomal cavity. The whole tentacle sheath possesses a regular mesh of muscles in Pectinatella and Cristatella, whereas circular muscles are limited to the tentacle sheath base in Hyalinella. This study is the first to describe muscles of the ring canal and contributes to reconstructing muscular features for the last common ancestor of all bryozoans. The data available suggest that two longitudinal muscle bands in the tentacles, as well as retractor muscles and longitudinal and circular muscles in the tentacle sheath, were present in the last common bryozoan ancestor. Comparisons among bryozoans shows that several apomorphies are present in the myoanatomy of each class- level taxon such as the epistomal musculature and musculature of the lophophoral arms in phylactolaemates, annular muscles in cyclostomes and parietal muscles in

  15. Effects of Early Motor Intervention in the Prone Position of Full-Term Infants through the First Year of Life.

    ERIC Educational Resources Information Center

    Douret, L.

    1993-01-01

    Full-term infants who had slept in the prone position since birth were followed to detect early postural abnormalities and differentiate potential peripheral abnormality from abnormalities of a central origin. Results showed that disappearance of initial signs of abnormality appeared to be muscular, and symptoms disappeared faster when a motor…

  16. Biochemical abnormalities in neonatal seizures.

    PubMed

    Sood, Arvind; Grover, Neelam; Sharma, Roshan

    2003-03-01

    The presence of seizure does not constitute a diagnoses but it is a symptom of an underlying central nervous system disorder due to systemic or biochemical disturbances. Biochemical disturbances occur frequently in the neonatal seizures either as an underlying cause or as an associated abnormality. In their presence, it is difficult to control seizure and there is a risk of further brain damage. Early recognition and treatment of biochemical disturbances is essential for optimal management and satisfactory long term outcome. The present study was conducted in the department of pediatrics in IGMC Shimla on 59 neonates. Biochemical abnormalities were detected in 29 (49.15%) of cases. Primary metabolic abnormalities occurred in 10(16.94%) cases of neonatal seizures, most common being hypocalcaemia followed by hypoglycemia, other metabolic abnormalities include hypomagnesaemia and hyponateremia. Biochemical abnormalities were seen in 19(38.77%) cases of non metabolic seizure in neonates. Associated metabolic abnormalities were observed more often with Hypoxic-ischemic-encephalopathy (11 out of 19) cases and hypoglycemia was most common in this group. No infant had hyponateremia, hyperkelemia or low zinc level.

  17. Imaging Flow Cytometry Analysis to Identify Differences of Survival Motor Neuron Protein Expression in Patients With Spinal Muscular Atrophy.

    PubMed

    Arakawa, Reiko; Arakawa, Masayuki; Kaneko, Kaori; Otsuki, Noriko; Aoki, Ryoko; Saito, Kayoko

    2016-08-01

    Spinal muscular atrophy is a neurodegenerative disorder caused by the deficient expression of survival motor neuron protein in motor neurons. A major goal of disease-modifying therapy is to increase survival motor neuron expression. Changes in survival motor neuron protein expression can be monitored via peripheral blood cells in patients; therefore we tested the sensitivity and utility of imaging flow cytometry for this purpose. After the immortalization of peripheral blood lymphocytes from a human healthy control subject and two patients with spinal muscular atrophy type 1 with two and three copies of SMN2 gene, respectively, we used imaging flow cytometry analysis to identify significant differences in survival motor neuron expression. A bright detail intensity analysis was used to investigate differences in the cellular localization of survival motor neuron protein. Survival motor neuron expression was significantly decreased in cells derived from patients with spinal muscular atrophy relative to those derived from a healthy control subject. Moreover, survival motor neuron expression correlated with the clinical severity of spinal muscular atrophy according to SMN2 copy number. The cellular accumulation of survival motor neuron protein was also significantly decreased in cells derived from patients with spinal muscular atrophy relative to those derived from a healthy control subject. The benefits of imaging flow cytometry for peripheral blood analysis include its capacities for analyzing heterogeneous cell populations; visualizing cell morphology; and evaluating the accumulation, localization, and expression of a target protein. Imaging flow cytometry analysis should be implemented in future studies to optimize its application as a tool for spinal muscular atrophy clinical trials. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Effects of exercise training on pulmonary vessel muscularization and right ventricular function in an animal model of COPD.

    PubMed

    Hassel, Erlend; Berre, Anne Marie; Skjulsvik, Anne Jarstein; Steinshamn, Sigurd

    2014-09-28

    Right ventricular dysfunction in COPD is common, even in the absence of pulmonary hypertension. The aim of the present study was to examine the effects of high intensity interval training (HIIT) on right ventricular (RV) function, as well as pulmonary blood vessel remodeling in a mouse model of COPD. 42 female A/JOlaHsd mice were randomized to exposure to either cigarette smoke or air for 6 hours/day, 5 days/week for 14 weeks. Mice from both groups were further randomized to sedentariness or HIIT for 4 weeks. Cardiac function was evaluated by echocardiography and muscularization of pulmonary vessel walls by immunohistochemistry. Smoke exposure induced RV systolic dysfunction demonstrated by reduced tricuspid annular plane systolic excursion. HIIT in smoke-exposed mice reversed RV dysfunction. There were no significant effects on the left ventricle of neither smoke exposure nor HIIT. Muscularization of the pulmonary vessels was reduced after exercise intervention, but no significant effects on muscularization were observed from smoke exposure. RV function was reduced in mice exposed to cigarette smoke. No Increase in pulmonary vessel muscularization was observed in these mice, implying that other mechanisms caused the RV dysfunction. HIIT attenuated the RV dysfunction in the smoke exposed mice. Reduced muscularization of the pulmonary vessels due to HIIT suggests that exercise training not only affects the heart muscle, but also has important effects on the pulmonary vasculature.

  19. Serum Creatinine Distinguishes Duchenne Muscular Dystrophy from Becker Muscular Dystrophy in Patients Aged ≤3 Years: A Retrospective Study

    PubMed Central

    Wang, Liang; Chen, Menglong; He, Ruojie; Sun, Yiming; Yang, Juan; Xiao, Lulu; Cao, Jiqing; Zhang, Huili; Zhang, Cheng

    2017-01-01

    Here, we investigated correlations between serum creatinine (SCRN) levels and clinical phenotypes of dystrophinopathy in young patients. Sixty-eight patients with dystrophinopathy at the Neuromuscular Clinic, The First Affiliated Hospital, Sun Yat-sen University, were selected for this study. The diagnosis of dystrophinopathy was based on clinical manifestation, biochemical changes, and molecular analysis. Some patients underwent muscle biopsies; SCRN levels were tested when patients were ≤3 years old, and reading frame changes were analyzed. Each patient was followed up, and motor function and clinical phenotype were assessed when the same patients were ≥4 years old. Our findings indicated that in young patients, lower SCRN levels were associated with increased disease severity (p < 0.01) and that SCRN levels were the highest in patients exhibiting mild Becker muscular dystrophy (BMD) (p < 0.001) and the lowest in patients with Duchenne muscular dystrophy (DMD) (p < 0.01) and were significantly higher in patients carrying in-frame mutations than in patients carrying out-of-frame mutations (p < 0.001). SCRN level cutoff values for identifying mild BMD [18 µmol/L; area under the curve (AUC): 0.947; p < 0.001] and DMD (17 µmol/L; AUC: 0.837; p < 0.001) were established. These results suggest that SCRN might be a valuable biomarker for distinguishing DMD from BMD in patients aged ≤3 years and could assist in the selection of appropriate treatment strategies. PMID:28533764

  20. Transport behaviors of locally fractional coupled Brownian motors with fluctuating interactions

    NASA Astrophysics Data System (ADS)

    Wang, Huiqi; Ni, Feixiang; Lin, Lifeng; Lv, Wangyong; Zhu, Hongqiang

    2018-09-01

    In some complex viscoelastic mediums, it is ubiquitous that absorbing and desorbing surrounding Brownian particles randomly occur in coupled systems. The conventional method is to model a variable-mass system driven by both multiplicative and additive noises. In this paper, an improved mathematical model is created based on generalized Langevin equations (GLE) to characterize the random interaction with locally fluctuating number of coupled particles in the elastically coupled factional Brownian motors (FBM). By the numerical simulations, the effect of fluctuating interactions on collective transport behaviors is investigated, and some abnormal phenomena, such as cooperative behaviors, stochastic resonance (SR) and anomalous transport, are observed in the regime of sub-diffusion.

  1. SIBLING CONCORDANCE FOR CLINICAL FEATURES OF DUCHENNE AND BECKER MUSCULAR DYSTROPHIES

    PubMed Central

    PETTYGROVE, SYDNEY; LU, ZHENQIANG; ANDREWS, JENNIFER G.; MEANEY, F. JOHN; SHEEHAN, DANIEL W.; PRICE, ELINORA T.; FOX, DEBORAH J.; PANDYA, SHREE; OUYANG, LIJING; APKON, SUSAN D.; POWIS, ZOE; CUNNIFF, CHRISTOPHER

    2015-01-01

    Introduction The correlation of markers of disease severity among brothers with Duchenne or Becker muscular dystrophy has implications for clinical guidance and clinical trials. Methods Sibling pairs with Duchenne or Becker muscular dystrophy (n = 60) were compared for ages when they reached clinical milestones of disease progression, including ceased ambulation, scoliosis of ≥ 20°, and development of cardiomyopathy. Results The median age at which younger brothers reached each milestone, compared with their older brothers ranged from 25 months younger for development of cardiomyopathy to 2 months older for ceased ambulation. For each additional month of ambulation by the older brother, the hazard of ceased ambulation by the younger brother decreased by 4%. Conclusions The ages when siblings reach clinical milestones of disease vary widely between siblings. However, the time to ceased ambulation for older brothers predicts the time to ceased ambulation for their younger brothers. PMID:24030636

  2. Phonological Awareness Skills in Young Boys with Duchenne Muscular Dystrophy

    ERIC Educational Resources Information Center

    Waring, Phoebe; Woodyatt, Gail

    2011-01-01

    Substantial research has detailed the reading deficits experienced by children with Duchenne muscular dystrophy (DMD). Although phonological awareness (PA) is vital in reading development, little is known about PA in the DMD population. This pilot study describes the PA abilities of a group of five young children with DMD, comparing the results…

  3. Implicit learning deficit in children with Duchenne muscular dystrophy: Evidence for a cerebellar cognitive impairment?

    PubMed

    Vicari, Stefano; Piccini, Giorgia; Mercuri, Eugenio; Battini, Roberta; Chieffo, Daniela; Bulgheroni, Sara; Pecini, Chiara; Lucibello, Simona; Lenzi, Sara; Moriconi, Federica; Pane, Marika; D'Amico, Adele; Astrea, Guja; Baranello, Giovanni; Riva, Daria; Cioni, Giovanni; Alfieri, Paolo

    2018-01-01

    This study aimed at comparing implicit sequence learning in individuals affected by Duchenne Muscular Dystrophy without intellectual disability and age-matched typically developing children. A modified version of the Serial Reaction Time task was administered to 32 Duchenne children and 37 controls of comparable chronological age. The Duchenne group showed a reduced rate of implicit learning even if in the absence of global intellectual disability. This finding provides further evidence of the involvement of specific aspects of cognitive function in Duchenne muscular dystrophy and on its possible neurobiological substrate.

  4. Dysferlin mediates membrane tubulation and links T-tubule biogenesis to muscular dystrophy.

    PubMed

    Hofhuis, Julia; Bersch, Kristina; Büssenschütt, Ronja; Drzymalski, Marzena; Liebetanz, David; Nikolaev, Viacheslav O; Wagner, Stefan; Maier, Lars S; Gärtner, Jutta; Klinge, Lars; Thoms, Sven

    2017-03-01

    The multi-C2 domain protein dysferlin localizes to the plasma membrane and the T-tubule system in skeletal muscle; however, its physiological mode of action is unknown. Mutations in the DYSF gene lead to autosomal recessive limb-girdle muscular dystrophy type 2B and Miyoshi myopathy. Here, we show that dysferlin has membrane tubulating capacity and that it shapes the T-tubule system. Dysferlin tubulates liposomes, generates a T-tubule-like membrane system in non-muscle cells, and links the recruitment of phosphatidylinositol 4,5-bisphosphate to the biogenesis of the T-tubule system. Pathogenic mutant forms interfere with all of these functions, indicating that muscular wasting and dystrophy are caused by the dysferlin mutants' inability to form a functional T-tubule membrane system. © 2017. Published by The Company of Biologists Ltd.

  5. The Mechanosensitive Ca2+ Channel as a Central Regular of Prostate Tumor Cell Migration and Invasiveness

    DTIC Science & Technology

    2009-01-01

    sibly explain why the absence of dystrophin in Duchenne muscular dystrophic muscle results in TRPC1 channels being abnormally gated open (see Sect...135 7/30/2007 6:35:10 PM 136 O.P. Hamill, R. Maroto 7.6.1.4 TRPC1 in Muscular Dystrophy Both TRPC1 and MscCa are expressed in skeletal muscle and...both have been implicated in the muscular degeneration that occurs in Duchenne muscular dystro- phy (DMD). In particular, muscle fibers from the mdx

  6. Chorionic villus sampling for abnormal screening compared to historical indications: prevalence of abnormal karyotypes.

    PubMed

    Marshall, Nicole E; Fraley, Gwen; Feist, Cori; Burns, Michael J; Pereira, Leonardo

    2012-08-01

    To determine the prevalence of abnormal karyotype results in women undergoing chorionic villus sampling (CVS) for abnormal first trimester screening compared to CVS for historical indications (advanced maternal age (AMA) or prior aneuploidy). Retrospective cohort of all patients undergoing CVS at Oregon Health & Science University from January 2006 to June 2010. Patients were separated based on CVS indication: (1) positive ultrasound (U/S) or serum screening; or (2) AMA or prior aneuploidy with normal or no screening. Prevalence of abnormal karyotype results were compared between groups. Fetal karyotyping was successful in 500 of 506 CVS procedures performed. 203 CVS were performed for positive screening with 69 abnormal karyotypes (34.0%). 264 CVS were performed for historical indications with 11 abnormal karyotypes (4.2%). This difference was statistically significant (χ(2) 71.9, p < 0.001; OR 11.8 [95% CI 5.8, 24.6]). There were two age-related aneuplodies in AMA women without positive screening. 42 out of 44 AMA women diagnosed with aneuploidy (95.5%) had abnormal U/S and/or serum screening (35 U/S, 4 serum, 3 U/S and serum). Combined ultrasound and serum screening should be recommended to all women, including AMA women, prior to undergoing invasive testing to improve risk-based counseling and minimize morbidity.

  7. Effects of Modified Pyramid System on Muscular Strength and Hypertrophy in Older Women.

    PubMed

    Dos Santos, Leandro; Ribeiro, Alex S; Cavalcante, Edilaine F; Nabuco, Hellen C; Antunes, Melissa; Schoenfeld, Brad J; Cyrino, Edilson S

    2018-06-26

    This study aimed to analyze the effects of a pyramid system performed with two repetition zones on muscular strength and skeletal muscle mass (SMM) in older women. Thirty-nine physically independent older women (67.8±5.4 years) were randomly assigned into one of two of groups that performed an 8-week resistance training program in an ascending pyramid fashion. Both groups performed 3 sets: a narrow repetition zone (NPR, n=20) with 12/10/8 repetitions, and a wide repetition zone (WPR, n=19) with 15/10/5 repetitions. The program consisted of 8 whole-body exercises, performed 3 times a week. Dual-energy X-ray absorptiometry was used to measure SMM, and muscular strength was evaluated by one-repetition maximum (1RM). Both groups increased (P<0.05) SMM (NPR=+ 4.7%, effect size=+ 0.34; WPR=+ 8.4%, effect size=+ 0.77), and total strength (NPR=+ 11.3%, effect size=+ 0.80; WPR=+ 13.8%, effect size=0.84), without statistical differences between them. Results suggest that both zones of repetitions in a pyramid system are effective strategies to improve muscular strength and muscle growth in older women. © Georg Thieme Verlag KG Stuttgart · New York.

  8. Short-term effect of volume recruitment-derecruitment manoeuvre on chest-wall motion in Duchenne muscular dystrophy.

    PubMed

    Meric, Henri; Falaize, Line; Pradon, Didier; Lacombe, Matthieu; Petitjean, Michel; Orlikowski, David; Prigent, Hélène; Lofaso, Frédéric

    2017-05-01

    Because progressive respiratory muscle weakness leads to decreased chest-wall motion with eventual ribcage stiffening, the purpose was to compare vital capacity (VC) and contributions of chest-wall compartments before and after volume recruitment-derecruitment manoeuvres (VRDM) in Duchenne muscular dystrophy (DMD). We studied nine patients with DMD and VC lower than 30% of predicted. VRDM was performed using 15 insufflations-exsufflations of +30 to -30 cmH 2 O. VC and three-dimensional chest-wall motion were measured, as well as oxygen saturation, transcutaneous partial pressure of carbon dioxide and the rapid shallow breathing index (respiratory rate/tidal volume) before (baseline) and immediately and 1 hour after VRDM. VC increased significantly immediately after VRDM (108% ± 7% of baseline, p = 0.018) but returned to baseline within 1 hour, and the rapid shallow breathing index increased significantly. The non-dominant side systematically increased immediately after VRDM ( p = 0.0077), and in the six patients with abnormal breathing asymmetry (difference >10% of VC) at baseline, this asymmetry was corrected immediately and/or 1 hour after VRDM. VRDM improved VC and reduced chest-wall motion asymmetry, but this beneficial effect waned rapidly with respiratory muscle fatigue, suggesting that VRDM may need to be repeated during the day to produce lasting benefits.

  9. Parental decision-making after ultrasound diagnosis of a serious foetal abnormality.

    PubMed

    Bijma, Hilmar H; Wildschut, Hajo I J; van der Heide, Agnes; Passchier, Jan; Wladimiroff, Juriy W; van der Maas, Paul J

    2005-01-01

    The purpose of this article is to provide clinicians who are involved in the field of foetal medicine with a comprehensive overview of theories that are relevant for the parental decision-making process after ultrasound diagnosis of a serious foetal abnormality. Since little data are available of parental decision-making after ultrasound diagnosis of foetal abnormality, we reviewed the literature on parental decision-making in genetic counselling of couples at increased genetic risk together with the literature on general decision-making theories. The findings were linked to the specific situation of parental decision-making after an ultrasound diagnosis of foetal abnormality. Based on genetic counselling studies, several cognitive mechanisms play a role in parental decision-making regarding future pregnancies. Parents often have a binary perception of risk. Probabilistic information is translated into two options: the child will or will not be affected. The graduality of chance seems to be of little importance in this process. Instead, the focus shifts to the possible consequences for future family life. General decision-making theories often focus on rationality and coherence of the decision-making process. However, studies of both the influence of framing and the influence of stress indicate that emotional mechanisms can have an important and beneficial function in the decision-making process. Cognitive mechanisms that are elicited by emotions and that are not necessarily rational can have an important and beneficial function in parental decision-making after ultrasound diagnosis of a foetal abnormality. Consequently, the process of parental decision-making should not solely be assessed on the basis of its rationality, but also on the basis of the parental emotional outcome. Copyright (c) 2005 S. Karger AG, Basel.

  10. Trajectory Adjustments Underlying Task-Specific Intermittent Force Behaviors and Muscular Rhythms

    PubMed Central

    Chen, Yi-Ching; Lin, Yen-Ting; Huang, Chien-Ting; Shih, Chia-Li; Yang, Zong-Ru; Hwang, Ing-Shiou

    2013-01-01

    Force intermittency is one of the major causes of motor variability. Focusing on the dynamics of force intermittency, this study was undertaken to investigate how force trajectory is fine-tuned for static and dynamic force-tracking of a comparable physical load. Twenty-two healthy adults performed two unilateral resistance protocols (static force-tracking at 75% maximal effort and dynamic force-tracking in the range of 50%–100% maximal effort) using the left hand. The electromyographic activity and force profile of the designated hand were monitored. Gripping force was off-line decomposed into a primary movement spectrally identical to the target motion and a force intermittency profile containing numerous force pulses. The results showed that dynamic force-tracking exhibited greater intermittency amplitude and force pulse but a smaller amplitude ratio of primary movement to force intermittency than static force-tracking. Multi-scale entropy analysis revealed that force intermittency during dynamic force-tracking was more complex on a low time scale but more regular on a high time scale than that of static force-tracking. Together with task-dependent force intermittency properties, dynamic force-tracking exhibited a smaller 8–12 Hz muscular oscillation but a more potentiated muscular oscillation at 35–50 Hz than static force-tracking. In conclusion, force intermittency reflects differing trajectory controls for static and dynamic force-tracking. The target goal of dynamic tracking is achieved through trajectory adjustments that are more intricate and more frequent than those of static tracking, pertaining to differing organizations and functioning of muscular oscillations in the alpha and gamma bands. PMID:24098640

  11. Changes in intranuclear mobility of mature snRNPs provide a mechanism for splicing defects in spinal muscular atrophy

    PubMed Central

    Clelland, Allyson Kara; Bales, Alexandra Beatrice E.; Sleeman, Judith Elizabeth

    2012-01-01

    It is becoming increasingly clear that defects in RNA metabolism can lead to disease. Spinal muscular atrophy (SMA), a leading genetic cause of infant mortality, results from insufficient amounts of survival motor neuron (SMN) protein. SMN is required for the biogenesis of small nuclear ribonucleoproteins (snRNPs): essential components of the spliceosome. Splicing abnormalities have been detected in models of SMA but it is unclear how lowered SMN affects the fidelity of pre-mRNA splicing. We have examined the dynamics of mature snRNPs in cells depleted of SMN and demonstrated that SMN depletion increases the mobility of mature snRNPs within the nucleus. To dissect the molecular mechanism by which SMN deficiency affects intranuclear snRNP mobility, we employed a panel of inhibitors of different stages of pre-mRNA processing. This in vivo modelling demonstrates that snRNP mobility is altered directly as a result of impaired snRNP maturation. Current models of nuclear dynamics predict that subnuclear structures, including the spliceosome, form by self-organization mediated by stochastic interactions between their molecular components. Thus, alteration of the intranuclear mobility of snRNPs provides a molecular mechanism for splicing defects in SMA. PMID:22393244

  12. Muscular power, neuromuscular activation, and performance in shot put athletes at preseason and at competition period.

    PubMed

    Kyriazis, Thomas A; Terzis, Gerasimos; Boudolos, Konstantinos; Georgiadis, Georgios

    2009-09-01

    The aim of this study was to investigate changes in shot put performance, muscular power, and neuromuscular activation of the lower extremities, between the preseason and the competition period, in skilled shot put athletes using the rotational technique. Shot put performance was assessed at the start of the pre-season period as well as after 12 weeks, at the competition period, in nine shot putters. Electromyographic (EMG) activity of the right vastus lateralis muscle was recorded during all shot put trials. Maximum squat strength (1RM) and mechanical parameters during the countermovement jump (CMJ) on a force platform were also determined at pre-season and at competition period. Shot put performance increased 4.7% (p < 0.05), while 1RM squat increased 6.5% (p < 0.025). EMG activity during the delivery phase was increased significantly (p < 0.025) after the training period. Shot put performance was significantly related with muscular power and takeoff velocity during the CMJ, at competition period (r = 0.66, p < 0.05 and 0.70, p < 0.05), but not with maximum vertical force. One RM squat was not related significantly with shot put performance. These results suggest that muscular power of the lower extremities is a better predictor of rotational shot put performance than absolute muscular strength in skilled athletes, at least during the competition period.

  13. Muscular Dystrophy, incurability, eugenics

    PubMed Central

    Rideau, Y; Rideau, F

    2007-01-01

    Summary The medical entity “muscular dystrophy” has been the object of a recent opinion campaign aimed at promoting a law in favour of euthanasia. This disease has become, in the eyes of the public, a media model of a particularly severe and incurable disease. This very widespread statement does not correspond to reality as far as concerns the life of these patients, to the condition that they have benefited from a very useful and fully provided empirical treatment. As already seen, the hope for life has already doubled, without clear limits. The idea of inducing an interruption when at death’s door, as long as a systematic prevention prior to birth, does not conform with the motivated opinion of the majority of patients consulted. On the contrary, the dogma of incurability may lead to dramatic individual consequences which should be stressed, from a medical viewpoint, on account of the unacceptable risks of social injustice or eugenics that this would imply. PMID:17915566

  14. Equine muscular dystrophy with myotonia.

    PubMed

    Montagna, P; Liguori, R; Monari, L; Strong, P N; Riva, R; Di Stasi, V; Gandini, G; Cipone, M

    2001-02-01

    To describe a case of equine muscular dystrophy with myotonia. A 5-year-old horse presented with hypertrophy and delayed relaxation of the muscles of the hindlimbs from age 2 months. Testicular atrophy developed from 2 years of age. Action and percussion myotonia was associated with weakness in these muscles, and EMG showed diffuse myotonic discharges and myopathic features. Biopsy of the gluteal muscle showed adipose and connective tissue infiltration, marked variation in muscle fibre size, and moth-eaten, ring and whorled fibres. Injection of apamin, a peptide blocker of calcium-activated potassium channels, which inhibits myotonia in human myotonic dystrophy, was ineffective in blocking myotonic discharges. Discharges promptly abated with 2% lidocaine injection. Myotonia in this horse is associated with dystrophic changes similar to human myotonic dystrophy, though there are some pharmacological differences.

  15. Experimental Treatment for Duchenne Muscular Dystrophy Gets Boost from Existing Medication

    MedlinePlus

    ... Boost from Existing Medication Spotlight on Research Experimental Treatment for Duchenne Muscular Dystrophy Gets Boost from Existing Medication By Colleen Labbe, M.S. | March 1, 2013 A mouse hanging on a wire during a test of muscle strength. Mice with a mutant dystrophin gene, which ...

  16. Dystrophin insufficiency causes a Becker muscular dystrophy-like phenotype in swine

    USDA-ARS?s Scientific Manuscript database

    Duchenne muscular dystrophy (DMD) is caused by a dystrophin deficiency while Becker MD is caused by a dystrophin insufficiency or expression of a partially functional dystrophin protein. Deficiencies in existing mouse and dog models necessitate the development of a novel large animal model. Our pu...

  17. Mechanisms of topical analgesics in relieving pain in an animal model of muscular inflammation.

    PubMed

    Duan, Wan-Ru; Lu, Jie; Xie, Yi-Kuan

    2013-09-01

    To investigate the possible mechanisms of topical analgesics in relieving pain in an animal model of muscular inflammation. Adult Sprague-Dawley rats of both sexes were injected with complete Freund's adjuvant to induce inflammation in the anterior tibialis muscle of left hindlimb. One of two types of topical analgesics: Xiaotong Tiegao (XTT), a Tibetan herb compound, or Capzasin (CAP), a cream containing 0.1% capsaicin, was applied to the skin over the inflamed anterior tibialis muscle. The following experiments were performed: pain behavioral tests, evaluation of plasma extravasation in the affected limb, and electrophysiological recordings of afferent nerve fibers. The behavioral experiments demonstrated that applications of either type of topical analgesic to the skin over the inflamed muscle significantly reduced muscular inflammatory pain, as indicated by the increased weight bearing capacity on the affected hindlimb (with latencies of 10 minutes for XTT and 1-2 hours for CAP). Meanwhile, both analgesics caused plasma extravasation in the affected skin. Electrophysiological recordings from the afferent fibers in the related cutaneous nerve indicated that topical analgesics selectively activated C-fibers, but not A-fibers innervating the same region of receptive field. The latency and duration of C-fiber activation was similar to those of the reduction of muscular inflammatory pain. On the contrary, topical analgesics substantially decreased C-fiber afferent spontaneous firing in the nerve innervating the inflamed muscle. Moreover, denervation of the affected skin blocked the analgesic effects of both topical analgesics in muscular inflammatory pain. This study suggests that topical analgesics may reduce the nociceptive input from inflamed muscles via a reflex mechanism by activating the cutaneous nociceptive afferents. Wiley Periodicals, Inc.

  18. Decreased Nocturnal Movements in Patients with Facioscapulohumeral Muscular Dystrophy

    PubMed Central

    Marca, Giacomo Della; Frusciante, Roberto; Dittoni, Serena; Vollono, Catello; Losurdo, Anna; Testani, Elisa; Scarano, Emanuele; Colicchio, Salvatore; Iannaccone, Elisabetta; Tonali, Pietro A.; Ricci, Enzo

    2010-01-01

    Study Objectives: Reduced mobility during sleep characterizes a variety of movement disorders and neuromuscular diseases. Facioscapulohumeral muscular dystrophy (FSHD) is the third most common form of muscular dystrophy in the general population, and people with FSHD have poor sleep quality. The aims of the present study were to evaluate nocturnal motor activity in patients with FSHD by means of videopolysomnography and to verify whether activity was associated with modifications in sleep structure. Methods: We enrolled 32 adult patients affected by genetically confirmed FSHD (18 women and 14 men, mean age 45.1 ± 13.4 years) and 32 matched control subjects, (18 women and 14 men, mean age 45.5 ± 11.4 years). Major body movements (MBM) were scored in videopolygraphic recordings in accordance with established criteria. An MBM index was calculated (number of MBM per hour of sleep). Results: The FSHD group showed a decrease in the MBM index (FSHD: 1.2 ± 1.1; control subjects: 2.3 ± 1.2, analysis of variance F = 13.672; p = 0.008). The sleep pattern of patients with FSHD, as compared with that of controls, was characterized by longer sleep latencies, shorter sleep durations, an increased percentage of wake during sleep, and a decreased percentage of rapid eye movement sleep. In the patient group, the MBM index was inversely correlated with severity of disease (Spearman test: r30 = −0.387; p < 0.05). Conclusions: The present findings suggest that patients with FSHD have a reduced number of nocturnal movements, which is related to disease severity. Reduced movement in bed may contribute to the sleep modifications observed in these patients. Citation: Marca GD; Frusciante R; Dittoni S; Vollono C; Losurdo A; Testani E; Scarano E; Colicchio S; Iannaccone E; Tonali PA; Ricci E. Decreased nocturnal movements in patients with facioscapulohumeral muscular dystrophy. J Clin Sleep Med 2010;6(3):276-280. PMID:20572422

  19. Anti-gravity training improves walking capacity and postural balance in patients with muscular dystrophy.

    PubMed

    Berthelsen, Martin Peter; Husu, Edith; Christensen, Sofie Bouschinger; Prahm, Kira Philipsen; Vissing, John; Jensen, Bente Rona

    2014-06-01

    Recent studies in patients with muscular dystrophies suggest positive effects of aerobic and strength training. These studies focused training on using bicycle ergometers and conventional strength training, which precludes more severely affected patients from participating, because of their weakness. We investigated the functional effects of combined aerobic and strength training in patients with Becker and limb-girdle muscular dystrophies with knee muscle strength levels as low as 3% of normal strength. Eight patients performed 10 weeks of aerobic and strength training on an anti-gravity treadmill, which offered weight support up to 80% of their body weight. Six minute walking distance, dynamic postural balance, and plasma creatine kinase were assessed 10 weeks prior to training, immediately before training and after 10 weeks of training. Training elicited an improvement of walking distance by 8±2% and dynamic postural balance by 13±4%, indicating an improved physical function. Plasma creatine kinase remained unchanged. These results provide evidence that a combination of aerobic and strength training during anti-gravity has the potential to safely improve functional ability in severely affected patients with Becker and limb-girdle muscular dystrophies. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Sensorimotor integration: basic concepts, abnormalities related to movement disorders and sensorimotor training-induced cortical reorganization.

    PubMed

    Machado, Sergio; Cunha, Marlo; Velasques, Bruna; Minc, Daniel; Teixeira, Silmar; Domingues, Clayton A; Silva, Julio G; Bastos, Victor H; Budde, Henning; Cagy, Mauricio; Basile, Luis; Piedade, Roberto; Ribeiro, Pedro

    2010-10-01

    Sensorimotor integration is defined as the capability of the central nervous system to integrate different sources of stimuli, and parallelly, to transform such inputs in motor actions. To review the basic principles of sensorimotor integration, such as, its neural bases and its elementary mechanisms involved in specific goal-directed tasks performed by healthy subjects, and the abnormalities reported in the most common movement disorders, such as, Parkinson' disease, dystonia and stroke, like the cortical reorganization-related mechanisms. Whether these disorders are associated with an abnormal peripheral sensory input or defective central processing is still unclear, but most of the data support a central mechanism. We found that the sensorimotor integration process plays a potential role in elementary mechanisms involved in specific goal-directed tasks performed by healthy subjects and in occurrence of abnormalities in most common movement disorders and, moreover, play a potential role on the acquisition of abilities that have as critical factor the coupling of different sensory data which will constitute the basis of elaboration of motor outputs consciously goal-directed.

  1. Preliminary diffusion tensor imaging studies in limb-girdle muscular dystrophies

    NASA Astrophysics Data System (ADS)

    Hidalgo-Tobon, S.; Hernandez-Salazar, G.; Vargas-Cañas, S.; Marrufo-Melendez, O.; Solis-Najera, S.; Taboada-Barajas, J.; Rodriguez, A. O.; Delgado-Hernandez, R.

    2012-10-01

    Limb-girdle muscular dystrophies (LGMD) are a group of autosomal dominantly or recessively inherited muscular dystrophies that also present with primary proximal (limb-girdle) muscle weakness. This type of dystrophy involves the shoulder and pelvic girdles, distinct phenotypic or clinical characteristics are recognized. Imaging experiments were conducted on a 1.5T GE scanner (General Electric Medical Systems. Milwaukee. USA), using a combination of two eight-channel coil array. Diffusion Tensor Imaging (DTI) data were acquired using a SE-EPI sequence, diffusion weighted gradients were applied along 30 non-collinear directions with a b-value=550 s/mm2. The connective tissue content does not appear to have a significant effect on the directionality of the diffusion, as assessed by fractional anisotropy. The fibers of the Sartorius muscle and gracilis showed decreased number of tracts, secondary to fatty infiltration and replacement of connective tissue and muscle mass loss characteristic of the underlying pathology. Our results demonstrated the utility of non-invasive MRI techniques to characterize the muscle pathology, through quantitative and qualitative methods such as the FA values and tractrography.

  2. Correction of Abdominal Distention by Biofeedback-Guided Control of Abdominothoracic Muscular Activity in a Randomized, Placebo-Controlled Trial.

    PubMed

    Barba, Elizabeth; Accarino, Anna; Azpiroz, Fernando

    2017-12-01

    Abdominal distention is produced by abnormal somatic postural tone. We developed an original biofeedback technique based on electromyography-guided control of abdominothoracic muscular activity. We performed a randomized, placebo-controlled study to demonstrate the superiority of biofeedback to placebo for the treatment of abdominal distention. At a referral center in Spain, we enrolled consecutive patients with visible abdominal distention who fulfilled the Rome III criteria for functional intestinal disorders (47 women, 1 man; 21-74 years old); 2 patients assigned to the placebo group withdrew and 2 patients assigned to biofeedback were not valid for analysis. Abdominothoracic muscle activity was recorded by electromyography. The patients in the biofeedback group were shown the signal and instructed to control muscle activity, whereas patients in the placebo received no instructions and were given oral simethicone. Each patient underwent 3 sessions over a 10-day period. The primary outcomes were subjective sensation of abdominal distention, measured by graphic rating scales for 10 consecutive days before and after the intervention. Patients in the biofeedback group effectively learned to reduce intercostal activity (by a mean 45% ± 3%), but not patients in the placebo group (reduced by a mean 5% ± 2%; P < .001). Patients in the biofeedback group learned to increase anterior wall muscle activity (by a mean 101% ± 10%), but not in the placebo group (decreased by a mean 4% ± 2%; P < .001). Biofeedback resulted in a 56% ± 1% reduction of abdominal distention (from a mean score of 4.6 ± 0.2 to 2.0 ± 0.2), whereas patients in the placebo group had a reduction of only 13% ± 8% (from a mean score of 4.7 ± 0.1 to 4.1 ± 0.4) (P < .001). In a randomized trial of patients with a functional intestinal disorder, we found that abdominal distention can be effectively corrected by biofeedback-guided control of abdominothoracic muscular activity, compared with placebo

  3. Chromosomal abnormalities in human sperm

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Martin, R.H.

    1985-01-01

    The ability to analyze human sperm chromosome complements after penetration of zona pellucida-free hamster eggs provides the first opportunity to study the frequency and type of chromosomal abnormalities in human gametes. Two large-scale studies have provided information on normal men. We have studied 1,426 sperm complements from 45 normal men and found an abnormality rate of 8.9%. Brandriff et al. (5) found 8.1% abnormal complements in 909 sperm from 4 men. The distribution of numerical and structural abnormalities was markedly dissimilar in the 2 studies. The frequency of aneuploidy was 5% in our sample and only 1.6% in Brandriff's, perhapsmore » reflecting individual variability among donors. The frequency of 24,YY sperm was low: 0/1,426 and 1/909. This suggests that the estimates of nondisjunction based on fluorescent Y body data (1% to 5%) are not accurate. We have also studied men at increased risk of sperm chromosomal abnormalities. The frequency of chromosomally unbalanced sperm in 6 men heterozygous for structural abnormalities varied dramatically: 77% for t11;22, 32% for t6;14, 19% for t5;18, 13% for t14;21, and 0% for inv 3 and 7. We have also studied 13 cancer patients before and after radiotherapy and demonstrated a significant dose-dependent increase of sperm chromosome abnormalities (numerical and structural) 36 months after radiation treatment.« less

  4. Directional abnormalities of vestibular and optokinetic responses in cerebellar disease

    NASA Technical Reports Server (NTRS)

    Walker, M. F.; Zee, D. S.; Shelhamer, M. J. (Principal Investigator)

    1999-01-01

    Directional abnormalities of vestibular and optokinetic responses in patients with cerebellar degeneration are reported. Three-axis magnetic search-coil recordings of the eye and head were performed in eight cerebellar patients. Among these patients, examples of directional cross-coupling were found during (1) high-frequency, high-acceleration head thrusts; (2) constant-velocity chair rotations with the head fixed; (3) constant-velocity optokinetic stimulation; and (4) following repetitive head shaking. Cross-coupling during horizontal head thrusts consisted of an inappropriate upward eye-velocity component. In some patients, sustained constant-velocity yaw-axis chair rotations produced a mixed horizontal-torsional nystagmus and/or an increase in the baseline vertical slow-phase velocity. Following horizontal head shaking, some patients showed an increase in the slow-phase velocity of their downbeat nystagmus. These various forms of cross-coupling did not necessarily occur to the same degree in a given patient; this suggests that different mechanisms may be responsible. It is suggested that cross-coupling during head thrusts may reflect a loss of calibration of brainstem connections involved in the direct vestibular pathways, perhaps due to dysfunction of the flocculus. Cross-coupling during constant-velocity rotations and following head shaking may result from a misorientation of the angular eye-velocity vector in the velocity-storage system. Finally, responses to horizontal optokinetic stimulation included an inappropriate torsional component in some patients. This suggests that the underlying organization of horizontal optokinetic tracking is in labyrinthine coordinates. The findings are also consistent with prior animal-lesion studies that have shown a role for the vestibulocerebellum in the control of the direction of the VOR.

  5. Clinical features of children and adults with a muscular dystrophy using powered indoor/outdoor wheelchairs: disease features, comorbidities and complications of disability.

    PubMed

    Frank, Andrew Oliver; De Souza, Lorraine H

    2018-05-01

    To describe the clinical features of electric powered indoor/outdoor wheelchair users with a muscular dystrophy, likely to influence optimal prescription; reflecting features of muscular dystrophies, conditions secondary to disability, and comorbidities impacting on equipment provision. Cross-sectional retrospective case note review of recipients of electric powered indoor/outdoor wheelchairs provided by a specialist regional wheelchair service. Data on demography, diagnostic/clinical, and wheelchair prescription were systematically extracted. Fifty-one men and 14 women, mean age 23.7 (range 10-67, s.d. 12.95) years, were studied. Forty had Duchenne muscular dystrophy, 22 had other forms of muscular dystrophy, and three were unclassified. Twenty-seven were aged under 19. Notable clinical features included problematic pain (10), cardiomyopathy (5), and ventilatory failure (4). Features related to disability were (kypho)scoliosis (20) and edema/cellulitis (3) whilst comorbidities included back pain (5). Comparison of younger with older users revealed younger users had more features of muscular dystrophy affecting electric powered chair provision (56%) whilst older users had more comorbidity (37%). Tilt-in-space was prescribed for 81% of users, specialized seating for 55% and complex controls for 16%. Muscular dystrophy users were prescribed electric powered indoor/outdoor chairs with many additional features reflecting the consequences of profound muscle weakness. In addition to facilitating independence and participation, electric powered indoor/outdoor chairs have major therapeutic benefits. Implications for rehabilitation Powered wheelchairs have therapeutic benefits in managing muscular dystrophy pain and weakness. The use of specialized seating needs careful consideration in supporting progressive muscle weakness and the management of scoliosis. Pain, discomfort, pressure risk, and muscle fatigue may be reduced by use of tilt-in-space.

  6. Specific profiles of neurocognitive and reading functions in a sample of 42 Italian boys with Duchenne Muscular Dystrophy.

    PubMed

    Lorusso, Maria Luisa; Civati, Federica; Molteni, Massimo; Turconi, Anna Carla; Bresolin, Nereo; D'Angelo, Maria Grazia

    2013-01-01

    A group of 42 Italian boys with Duchenne Muscular Dystrophy was compared with a control group of 10 boys with Spinal Muscular Atrophy and Osteogenesis Imperfecta on tests assessing general intellectual ability, language, neuropsychological functions, and reading skills with the aim of describing a comprehensive profile of the various functions and investigating their interrelationships. The influence of general intellectual level on performance was analyzed. Further, correlations between various neuropsychological measures and language performances were computed for the group with Duchenne Muscular Dystrophy, as well as the correlations between reading scores and other cognitive and linguistic measures. A general lowering in VIQ, PIQ, and FSIQ scores was found to characterize the group with Duchenne Muscular Dystrophy. Expressive language skills were within the normal range, while syntactic and grammatical comprehension were significantly impaired. The presence of below-average reading performances was further confirmed. However, unlike previous studies on irregular orthographies, the present results show that (a) the mild reading difficulties found in the sample essentially concern speed rather than accuracy; (b) they concern word rather than nonword reading; (c) lower reading performances are related to lower scores in general IQ; (d) no correlations emerge with phonological abilities, verbal short-term memory, or working memory, but rather with long-term memory and lexical skills. This may suggest that language-specific effects modulate the cognitive expressions of Duchenne Muscular Dystrophy and raises the possibility that the dysfunctions underlying the reading difficulties observed in affected readers of regular orthographies involve different neurocognitive systems than the cortico-cerebellar circuits usually invoked.

  7. Playground Apparatus Experience and Muscular Endurance among Children 4-6.

    ERIC Educational Resources Information Center

    Gabbard, Carl

    The effects of specific play apparatus experience on a test of upper body muscular endurance was investigated among a group of children 4-6 years old. Both the control and experimental group consisted of 45 subjects randomly selected on the basis of age from two private day care centers situated in the same community. The two groups were of…

  8. The Assessment of Intelligence in Boys with Duchenne Muscular Dystrophy.

    ERIC Educational Resources Information Center

    Mearig, Judith S.

    1979-01-01

    Challenges assumptions and research procedures leading to the position that below-average intellectual potential is an integral part of Duchenne muscular dystrophy. A study of 58 boys (ages 5 to 18) from urban, suburban, and rural settings indicated IQ range of 59 to 131 and no evidence of significant verbal deficit (reported in earlier studies).…

  9. Generation of muscular dystrophy model rats with a CRISPR/Cas system.

    PubMed

    Nakamura, Katsuyuki; Fujii, Wataru; Tsuboi, Masaya; Tanihata, Jun; Teramoto, Naomi; Takeuchi, Shiho; Naito, Kunihiko; Yamanouchi, Keitaro; Nishihara, Masugi

    2014-07-09

    Duchenne muscular dystrophy (DMD) is an X-linked lethal muscle disorder caused by mutations in the Dmd gene encoding Dystrophin. DMD model animals, such as mdx mice and canine X-linked muscular dystrophy dogs, have been widely utilized in the development of a treatment for DMD. Here, we demonstrate the generation of Dmd-mutated rats using a clustered interspaced short palindromic repeats (CRISPR)/Cas system, an RNA-based genome engineering technique that is also adaptive to rats. We simultaneously targeted two exons in the rat Dmd gene, which resulted in the absence of Dystrophin expression in the F0 generation. Dmd-mutated rats exhibited a decline in muscle strength, and the emergence of degenerative/regenerative phenotypes in the skeletal muscle, heart, and diaphragm. These mutations were heritable by the next generation, and F1 male rats exhibited similar phenotypes in their skeletal muscles. These model rats should prove to be useful for developing therapeutic methods to treat DMD.

  10. Psychometric properties of the Drive for Muscularity Scale in Malay men.

    PubMed

    Swami, Viren; Barron, David; Lau, Poh Li; Jaafar, Jas Laile

    2016-06-01

    The Drive for Muscularity Scale (DMS) is a widely used measure in studies of men's body image, but few studies have examined its psychometric properties outside English-speaking samples. Here, we assessed the factor structure of a Malay translation of the DMS. A community sample of 159 Malay men from Kuala Lumpur, Malaysia, completed the DMS, along with measures of self-esteem, body appreciation, and muscle discrepancy. Exploratory factor analysis led to the extraction of two factors, differentiating attitudes from behaviours, which mirrors the parent scale. Both factors also loaded on to a higher-order drive for muscularity factor. The subscales of the Malay DMS had adequate internal consistencies and good convergent validity, insofar as significant relationships were reported with self-esteem, body appreciation, muscle discrepancy, and body mass index. These results indicate that the Malay DMS has acceptable psychometric properties and can be used to assess body image concerns in Malay men. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Upper Girdle Imaging in Facioscapulohumeral Muscular Dystrophy

    PubMed Central

    Tasca, Giorgio; Monforte, Mauro; Iannaccone, Elisabetta; Laschena, Francesco; Ottaviani, Pierfrancesco; Leoncini, Emanuele; Boccia, Stefania; Galluzzi, Giuliana; Pelliccioni, Marco; Masciullo, Marcella; Frusciante, Roberto; Mercuri, Eugenio; Ricci, Enzo

    2014-01-01

    Background In Facioscapulohumeral muscular dystrophy (FSHD), the upper girdle is early involved and often difficult to assess only relying on physical examination. Our aim was to evaluate the pattern and degree of involvement of upper girdle muscles in FSHD compared with other muscle diseases with scapular girdle impairment. Methods We propose an MRI protocol evaluating neck and upper girdle muscles. One hundred-eight consecutive symptomatic FSHD patients and 45 patients affected by muscular dystrophies and myopathies with prominent upper girdle involvement underwent this protocol. Acquired scans were retrospectively analyzed. Results The trapezius (100% of the patients) and serratus anterior (85% of the patients) were the most and earliest affected muscles in FSHD, followed by the latissimus dorsi and pectoralis major, whilst spinati and subscapularis (involved in less than 4% of the patients) were consistently spared even in late disease stages. Asymmetry and hyperintensities on short-tau inversion recovery (STIR) sequences were common features, and STIR hyperintensities could also be found in muscles not showing signs of fatty replacement. The overall involvement appears to be disease-specific in FSHD as it significantly differed from that encountered in the other myopathies. Conclusions The detailed knowledge of single muscle involvement provides useful information for correctly evaluating patients' motor function and to set a baseline for natural history studies. Upper girdle imaging can also be used as an additional tool helpful in supporting the diagnosis of FSHD in unclear situations, and may contribute with hints on the currently largely unknown molecular pathogenesis of this disease. PMID:24932477

  12. Effects of intensity and duration of exercise on muscular responses to training of thoroughbred racehorses.

    PubMed

    Rivero, José-Luis L; Ruz, Antonio; Martí-Korff, Silvia; Estepa, José-Carlos; Aguilera-Tejero, Escolástico; Werkman, Jutta; Sobotta, Mathias; Lindner, Arno

    2007-05-01

    This study examined the effects of the intensity and duration of exercise on the nature and magnitude of training adaptations in muscle of adolescent (2-3 yr old) racehorses. Six thoroughbreds that had been pretrained for 2 mo performed six consecutive conditioning programs of varying lactate-guided intensities [velocities eliciting blood lactate concentrations of 2.5 mmol/l (v2.5) and 4 mmol/l (v4), respectively] and durations (5, 15, 25 min). Pre- and posttraining gluteus muscle biopsies were analyzed for myosin heavy chain content, fiber-type composition, fiber size, capillarization, and fiber histochemical oxidative and glycolytic capabilities. Although training adaptations were similar in nature, they varied greatly in magnitude among the different training protocols. Overall, the use of v4 as the exercise intensity for 25 min elicited the most consistent training adaptations in muscle, whereas the minimal training stimulus that evoked any significant change was identified with exercises of 15 min at v2.5. Within this range, muscular adaptations showed significant trends to be proportional to the exercise load of specific training programs. Taken together, these data suggest that muscular adaptations to training in horses occur on a continuum that is based on the exercise intensity and duration of training. The practical implications of this study are that exercises for 15 to 25 min/day at velocities between v2.5 and v4 can improve in the short term (3 wk) the muscular stamina in thoroughbreds. However, exercises of 5-15 min at v4 are necessary to enhance muscular features related to strength (hypertrophy).

  13. Myostatin inhibition by a follistatin-derived peptide ameliorates the pathophysiology of muscular dystrophy model mice.

    PubMed

    Tsuchida, K

    2008-07-01

    Gene-targeted therapies, such as adeno-associated viral vector (AAV)-mediated gene therapy and cell-mediated therapy using myogenic stem cells, are hopeful molecular strategies for muscular dystrophy. In addition, drug therapies based on the pathophysiology of muscular dystrophy patients are desirable. Multidisciplinary approaches to drug design would offer promising therapeutic strategies. Myostatin, a member of the transforming growth factor-beta superfamily, is predominantly produced by skeletal muscle and negatively regulates the growth and differentiation of cells of the skeletal muscle lineage. Myostatin inhibition would increase the skeletal muscle mass and prevent muscle degeneration, regardless of the type of muscular dystrophy. Myostatin inhibitors include myostatin antibodies, myostatin propeptide, follistatin and follistatin-related protein. Although follistatin possesses potent myostatin-inhibiting activity, it works as an efficient inhibitor of activins. Unlike myostatin, activins regulate the growth and differentiation of nearly all cell types, including cells of the gonads, pituitary gland and skeletal muscle. We have developed a myostatin-specific inhibitor derived from follistatin, designated FS I-I. Transgenic mice expressing this myostatin-inhibiting peptide under the control of a skeletal muscle-specific promoter showed increased skeletal muscle mass and strength. mdx mice were crossed with FS I-I transgenic mice and any improvement of the pathological signs was investigated. The resulting mdx/FS I-I mice exhibited increased skeletal muscle mass and reduced cell infiltration in muscles. Muscle strength was also recovered in mdx/FS I-I mice. Our data indicate that myostatin inhibition by this follistatin-derived peptide has therapeutic potential for muscular dystrophy.

  14. Cardiorespiratory Fitness and Muscular Strength as Mediators of the Influence of Fatness on Academic Achievement.

    PubMed

    García-Hermoso, Antonio; Esteban-Cornejo, Irene; Olloquequi, Jordi; Ramírez-Vélez, Robinson

    2017-08-01

    To examine the combined association of fatness and physical fitness components (cardiorespiratory fitness [CRF] and muscular strength) with academic achievement, and to determine whether CRF and muscular strength are mediators of the association between fatness and academic achievement in a nationally representative sample of adolescents from Chile. Data were obtained for a sample of 36 870 adolescents (mean age, 13.8 years; 55.2% boys) from the Chilean System for the Assessment of Educational Quality test for eighth grade in 2011, 2013, and 2014. Physical fitness tests included CRF (20-m shuttle run) and muscular strength (standing long jump). Weight, height, and waist circumference were assessed, and body mass index and waist circumference-to-height ratio were calculated. Academic achievement in language and mathematics was assessed using standardized tests. The PROCESS script developed by Hayes was used for mediation analysis. Compared with unfit and high-fatness adolescents, fit and low-fatness adolescents had significantly higher odds for attaining high academic achievement in language and mathematics. However, in language, unfit and low-fatness adolescents did not have significantly higher odds for obtaining high academic achievement. Those with high fatness had higher academic achievement (both language and mathematics) if they were fit. Linear regression models suggest a partial or full mediation of physical fitness in the association of fatness variables with academic achievement. CRF and muscular strength may attenuate or even counteract the adverse influence of fatness on academic achievement in adolescents. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Elderly Onset of Weakness in Facioscapulohumeral Muscular Dystrophy

    PubMed Central

    Fee, Dominic B.

    2012-01-01

    A 77-year-old male is presented. He had onset of proximal weakness 10 years earlier. His course was slowly progressive. Despite having phenotypic features of facioscapulohumeral muscular dystrophy (FSH), genetic testing for this was delayed because of his age of onset, lack of family history, and benign appearing muscle biopsy. This case is one of the oldest onset of weakness in genetically confirmed FSH and highlights the recognized expansion in phenotype that has occurred since the advent of genetic testing. PMID:23024867

  16. Elderly onset of weakness in facioscapulohumeral muscular dystrophy.

    PubMed

    Fee, Dominic B

    2012-01-01

    A 77-year-old male is presented. He had onset of proximal weakness 10 years earlier. His course was slowly progressive. Despite having phenotypic features of facioscapulohumeral muscular dystrophy (FSH), genetic testing for this was delayed because of his age of onset, lack of family history, and benign appearing muscle biopsy. This case is one of the oldest onset of weakness in genetically confirmed FSH and highlights the recognized expansion in phenotype that has occurred since the advent of genetic testing.

  17. Improved Muscle Function in Duchenne Muscular Dystrophy through L-Arginine and Metformin: An Investigator-Initiated, Open-Label, Single-Center, Proof-Of-Concept-Study.

    PubMed

    Hafner, Patricia; Bonati, Ulrike; Erne, Beat; Schmid, Maurice; Rubino, Daniela; Pohlman, Urs; Peters, Thomas; Rutz, Erich; Frank, Stephan; Neuhaus, Cornelia; Deuster, Stefanie; Gloor, Monika; Bieri, Oliver; Fischmann, Arne; Sinnreich, Michael; Gueven, Nuri; Fischer, Dirk

    2016-01-01

    Altered neuronal nitric oxide synthase function in Duchenne muscular dystrophy leads to impaired mitochondrial function which is thought to be one cause of muscle damage in this disease. The study tested if increased intramuscular nitric oxide concentration can improve mitochondrial energy metabolism in Duchenne muscular dystrophy using a novel therapeutic approach through the combination of L-arginine with metformin. Five ambulatory, genetically confirmed Duchenne muscular dystrophy patients aged between 7–10 years were treated with L-arginine (3 x 2.5 g/d) and metformin (2 x 250 mg/d) for 16 weeks. Treatment effects were assessed using mitochondrial protein expression analysis in muscular biopsies, indirect calorimetry, Dual-Energy X-Ray Absorptiometry, quantitative thigh muscle MRI, and clinical scores of muscle performance. There were no serious side effects and no patient dropped out. Muscle biopsy results showed pre-treatment a significantly reduced mitochondrial protein expression and increased oxidative stress in Duchenne muscular dystrophy patients compared to controls. Post-treatment a significant elevation of proteins of the mitochondrial electron transport chain was observed as well as a reduction in oxidative stress. Treatment also decreased resting energy expenditure rates and energy substrate use shifted from carbohydrates to fatty acids. These changes were associated with improved clinical scores. In conclusion pharmacological stimulation of the nitric oxide pathway leads to improved mitochondria function and clinically a slowing of disease progression in Duchenne muscular dystrophy. This study shall lead to further development of this novel therapeutic approach into a real alternative for Duchenne muscular dystrophy patients. ClinicalTrials.gov NCT02516085.

  18. [Comparison of cardiopulmonary endurance and muscular fitness in teenagers between Hong Kong and inland cities].

    PubMed

    Hong, Y; Chan, K; Wang, Y

    1997-01-01

    A study on the data of the physique investigated in teenagers was carried out between Hong Kong and inland cities to compare their cardiopulmonary endurance and muscular fitness. Results revealed that cardiopulmonary endurance in school teenagers of both sex at different ages in inland cities was better than that in Hong Kong. Muscular strength and endurance of sports performance of teenagers, except for standing long jump, in Hong Kong were weaker than that in inland cities. It suggests that attention should be paid to the involvement of teenagers in physical education with the increase of people's living standard.

  19. Evaluation of Narrative Abilities in Patients Suffering from Duchenne Muscular Dystrophy

    ERIC Educational Resources Information Center

    Marini, A.; Lorusso, M. L.; D'Angelo, M. G.; Civati, F.; Turconi, A. C.; Fabbro, F.; Bresolin, N.

    2007-01-01

    The present work investigated cognitive, linguistic and narrative abilities in a group of children suffering from Duchenne Muscular Dystrophy, an allelic X-linked recessive disorder caused by mutations in the gene encoding dystrophin. The patients showed mildly reduced IQ with lower Verbal than Performance Intelligence Quotient and were mildly…

  20. Serum Creatinine Distinguishes Duchenne Muscular Dystrophy from Becker Muscular Dystrophy in Patients Aged ≤3 Years: A Retrospective Study.

    PubMed

    Wang, Liang; Chen, Menglong; He, Ruojie; Sun, Yiming; Yang, Juan; Xiao, Lulu; Cao, Jiqing; Zhang, Huili; Zhang, Cheng

    2017-01-01

    Here, we investigated correlations between serum creatinine (SCRN) levels and clinical phenotypes of dystrophinopathy in young patients. Sixty-eight patients with dystrophinopathy at the Neuromuscular Clinic, The First Affiliated Hospital, Sun Yat-sen University, were selected for this study. The diagnosis of dystrophinopathy was based on clinical manifestation, biochemical changes, and molecular analysis. Some patients underwent muscle biopsies; SCRN levels were tested when patients were ≤3 years old, and reading frame changes were analyzed. Each patient was followed up, and motor function and clinical phenotype were assessed when the same patients were ≥4 years old. Our findings indicated that in young patients, lower SCRN levels were associated with increased disease severity ( p  < 0.01) and that SCRN levels were the highest in patients exhibiting mild Becker muscular dystrophy (BMD) ( p  < 0.001) and the lowest in patients with Duchenne muscular dystrophy (DMD) ( p  < 0.01) and were significantly higher in patients carrying in-frame mutations than in patients carrying out-of-frame mutations ( p  < 0.001). SCRN level cutoff values for identifying mild BMD [18 µmol/L; area under the curve (AUC): 0.947; p  < 0.001] and DMD (17 µmol/L; AUC: 0.837; p  < 0.001) were established. These results suggest that SCRN might be a valuable biomarker for distinguishing DMD from BMD in patients aged ≤3 years and could assist in the selection of appropriate treatment strategies.