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Sample records for claw muscle atrophy

  1. Ca2+-dependent proteolytic activity in crab claw muscle: effects of inhibitors and specificity for myofibrillar proteins

    International Nuclear Information System (INIS)

    Mykles, D.L.; Skinner, D.M.

    1983-01-01

    The claw closer muscle of the Bermuda land crab, Gecarcinus lateralis, undergoes a sequential atrophy and restoration during each molting cycle. The role of Ca 2+ -dependent proteinases in the turn-over of myofibrillar protein in normal anecdysial (intermolt) claw muscle is described. Crab Ca 2+ -dependent proteinase degrades the myofibrillar proteins actin, myosin heavy and light chains, paramyosin, tropomyosin, and troponin-T and -I. Ca 2+ -dependent proteinase activity in whole homogenates and 90,000 x g supernatant fractions from muscle homogenates has been characterized with respect to Ca 2+ requirement, substrate specificity, and effects of proteinase inhibitors. The enzyme is inhibited by antipain, leupeptin, E-64, and iodoacetamide; it is insensitive to pepstatin A. The specificity of crab Ca 2+ -dependent proteinase was examined with native myosin with normal ATPase activity as well as with radioiodinated myosin and radioiodinated hemolymph proteins. Hydrolysis of 125 I-myosin occurs in two phases, both Ca 2+ -dependent: (1) heavy chain (M/sub r/ = 200,000) is cleaved into four large fragments (M/sub r/ = 160,000, 110,000, 73,000, 60,000) and numerous smaller fragments; light chain (M/sub r/ = 18,000) is cleaved to a 15,000-Da fragment; (2) the fragments produced in the first phase are hydrolyzed to acid-soluble material. Although radioiodinated native hemolymph proteins are not susceptible to the Ca 2+ -dependent proteinase, those denatured by carboxymethylation are degraded. These data suggest that crab Ca 2+ -dependent proteinase is involved in turnover of myofibrillar protein in normal muscle and muscle undergoing proecdysial atrophy

  2. Skeletal muscle atrophy in bioengineered skeletal muscle: a new model system.

    Science.gov (United States)

    Lee, Peter H U; Vandenburgh, Herman H

    2013-10-01

    Skeletal muscle atrophy has been well characterized in various animal models, and while certain pathways that lead to disuse atrophy and its associated functional deficits have been well studied, available drugs to counteract these deficiencies are limited. An ex vivo tissue-engineered skeletal muscle offers a unique opportunity to study skeletal muscle physiology in a controlled in vitro setting. Primary mouse myoblasts isolated from adult muscle were tissue engineered into bioartificial muscles (BAMs) containing hundreds of aligned postmitotic muscle fibers expressing sarcomeric proteins. When electrically stimulated, BAMs generated measureable active forces within 2-3 days of formation. The maximum isometric tetanic force (Po) increased for ∼3 weeks to 2587±502 μN/BAM and was maintained at this level for greater than 80 days. When BAMs were reduced in length by 25% to 50%, muscle atrophy occurred in as little as 6 days. Length reduction resulted in significant decreases in Po (50.4%), mean myofiber cross-sectional area (21.7%), total protein synthesis rate (22.0%), and noncollagenous protein content (6.9%). No significant changes occurred in either the total metabolic activity or protein degradation rates. This study is the first in vitro demonstration that length reduction alone can induce skeletal muscle atrophy, and establishes a novel in vitro model for the study of skeletal muscle atrophy.

  3. Characterization of disuse skeletal muscle atrophy and the efficacy of a novel muscle atrophy countermeasure during spaceflight and simulated microgravity

    Science.gov (United States)

    Hanson, Andrea Marie

    Humans are an integral part of the engineered systems that will enable return to the Moon and eventually travel to Mars. Major advancements in countermeasure development addressing deleterious effects of microgravity and reduced gravity on the musculoskeletal system need to be made to ensure mission safety and success. The primary objectives of this dissertation are to advance the knowledge and understanding of skeletal muscle atrophy, and support development of novel countermeasures for disuse atrophy to enable healthy long-duration human spaceflight. Models simulating microgravity and actual spaceflight were used to examine the musculoskeletal adaptations during periods of unloading. Myostatin inhibition, a novel anti-atrophy drug therapy, and exercise were examined as a means of preventing and recovering from disuse atrophy. A combination of assays was used to quantify adaptation responses to unloading and examine efficacy of the countermeasures. Body and muscle masses were collected to analyze systemic changes due to treatments. Hindlimb strength and individual muscle forces were measured to demonstrate functional adaptations to treatments. Muscle fiber morphology and myosin heavy chain (MHC) expression was examined to identify adaptations at the cellular level. Protein synthesis signals insulin-like growth factor-1 (IGF-1), Akt, and p70s6 kinase; and the degradation signals Atrogin-1 and MuRF-1 were examined to identify adaptations at the molecular level that ultimately lead to muscle hypertrophy and atrophy. A time course study provided a thorough characterization of the adaptation of skeletal muscle during unloading in C57BL/6 mice, and baseline data for comparison to and evaluation of subsequent studies. Time points defining the on-set and endpoints of disuse muscle atrophy were identified to enable characterization of rapid vs. long-term responses of skeletal muscle to hindlimb suspension. Unloading-induced atrophy primarily resulted from increased protein

  4. Cellular and molecular mechanisms of muscle atrophy

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    Paolo Bonaldo

    2013-01-01

    Full Text Available Skeletal muscle is a plastic organ that is maintained by multiple pathways regulating cell and protein turnover. During muscle atrophy, proteolytic systems are activated, and contractile proteins and organelles are removed, resulting in the shrinkage of muscle fibers. Excessive loss of muscle mass is associated with poor prognosis in several diseases, including myopathies and muscular dystrophies, as well as in systemic disorders such as cancer, diabetes, sepsis and heart failure. Muscle loss also occurs during aging. In this paper, we review the key mechanisms that regulate the turnover of contractile proteins and organelles in muscle tissue, and discuss how impairments in these mechanisms can contribute to muscle atrophy. We also discuss how protein synthesis and degradation are coordinately regulated by signaling pathways that are influenced by mechanical stress, physical activity, and the availability of nutrients and growth factors. Understanding how these pathways regulate muscle mass will provide new therapeutic targets for the prevention and treatment of muscle atrophy in metabolic and neuromuscular diseases.

  5. Botulinum Toxin and Muscle Atrophy: A Wanted or Unwanted Effect.

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    Durand, Paul D; Couto, Rafael A; Isakov, Raymond; Yoo, Donald B; Azizzadeh, Babak; Guyuron, Bahman; Zins, James E

    2016-04-01

    While the facial rejuvenating effect of botulinum toxin type A is well known and widespread, its use in body and facial contouring is less common. We first describe its use for deliberate muscle volume reduction, and then document instances of unanticipated and undesirable muscle atrophy. Finally, we investigate the potential long-term adverse effects of botulinum toxin-induced muscle atrophy. Although the use of botulinum toxin type A in the cosmetic patient has been extensively studied, there are several questions yet to be addressed. Does prolonged botulinum toxin treatment increase its duration of action? What is the mechanism of muscle atrophy and what is the cause of its reversibility once treatment has stopped? We proceed to examine how prolonged chemodenervation with botulinum toxin can increase its duration of effect and potentially contribute to muscle atrophy. Instances of inadvertent botulinum toxin-induced atrophy are also described. These include the "hourglass deformity" secondary to botulinum toxin type A treatment for migraine headaches, and a patient with atrophy of multiple facial muscles from injections for hemifacial spasm. Numerous reports demonstrate that muscle atrophy after botulinum toxin type A treatment occurs and is both reversible and temporary, with current literature supporting the notion that repeated chemodenervation with botulinum toxin likely responsible for both therapeutic and incidental temporary muscle atrophy. Furthermore, duration of response may be increased with subsequent treatments, thus minimizing frequency of reinjection. Practitioners should be aware of the temporary and reversible effect of botulinum toxin-induced muscle atrophy and be prepared to reassure patients on this matter. © 2016 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.

  6. Biochemical adaptations of antigravity muscle fibers to disuse atrophy

    Science.gov (United States)

    Booth, F. W.

    1978-01-01

    Studies are presented in four parts of this report. The four parts include; (1) studies to gain information on the molecular basis of atrophy by antigravity muscle; (2) studies on the work capacity of antigravity muscles during atrophy and during recovery from atrophy; (3) studies on recovery of degenerated antigravity fibers after removal of hind-limb casts; and (4) studies on the atrophy and recovery of bone. The philosophy of these studies was to identify the time sequence of events in the soleus muscle of the rat following immobilization of the hind limbs, so that the length of the soleus muscle within the fixed limb is less than its resting length. In two separate studies, no decline in the weight of the soleus muscle could be detected during the first 72 hours of limb immobilization.

  7. Effect of Oenothera odorata Root Extract on Microgravity and Disuse-Induced Muscle Atrophy.

    Science.gov (United States)

    Lee, Yong-Hyeon; Seo, Dong-Hyun; Park, Ji-Hyung; Kabayama, Kazuya; Opitz, Joerg; Lee, Kwang Ho; Kim, Han-Sung; Kim, Tack-Joong

    2015-01-01

    Muscle atrophy, a reduction of muscle mass, strength, and volume, results from reduced muscle use and plays a key role in various muscular diseases. In the microgravity environment of space especially, muscle atrophy is induced by muscle inactivity. Exposure to microgravity induces muscle atrophy through several biological effects, including associations with reactive oxygen species (ROS). This study used 3D-clinostat to investigate muscle atrophy caused by oxidative stress in vitro, and sciatic denervation was used to investigate muscle atrophy in vivo. We assessed the effect of Oenothera odorata root extract (EVP) on muscle atrophy. EVP helped recover cell viability in C2C12 myoblasts exposed to microgravity for 24 h and delayed muscle atrophy in sciatic denervated mice. However, the expressions of HSP70, SOD1, and ceramide in microgravity-exposed C2C12 myoblasts and in sciatic denervated mice were either decreased or completely inhibited. These results suggested that EVP can be expected to have a positive effect on muscle atrophy by disuse and microgravity. In addition, EVP helped characterize the antioxidant function in muscle atrophy.

  8. Can endurance exercise preconditioning prevention disuse muscle atrophy?

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    Michael P Wiggs

    2015-03-01

    Full Text Available Emerging evidence suggests that exercise training can provide a level of protection against disuse muscle atrophy. Endurance exercise training imposes oxidative, metabolic, and heat stress on skeletal muscle which activates a variety of cellular signaling pathways that ultimately leads to the increased expression of proteins that have been demonstrated to protect muscle from inactivity –induced atrophy. This review will highlight the effect of exercise-induced oxidative stress on endogenous enzymatic antioxidant capacity (i.e., superoxide dismutase, glutathione peroxidase, and catalase, the role of oxidative and metabolic stress on PGC1-α, and finally highlight the effect heat stress and HSP70 induction. Finally, this review will discuss the supporting scientific evidence that these proteins can attenuate muscle atrophy through exercise preconditioning.

  9. Effect of Oenothera odorata Root Extract on Microgravity and Disuse-Induced Muscle Atrophy

    Directory of Open Access Journals (Sweden)

    Yong-Hyeon Lee

    2015-01-01

    Full Text Available Muscle atrophy, a reduction of muscle mass, strength, and volume, results from reduced muscle use and plays a key role in various muscular diseases. In the microgravity environment of space especially, muscle atrophy is induced by muscle inactivity. Exposure to microgravity induces muscle atrophy through several biological effects, including associations with reactive oxygen species (ROS. This study used 3D-clinostat to investigate muscle atrophy caused by oxidative stress in vitro, and sciatic denervation was used to investigate muscle atrophy in vivo. We assessed the effect of Oenothera odorata root extract (EVP on muscle atrophy. EVP helped recover cell viability in C2C12 myoblasts exposed to microgravity for 24 h and delayed muscle atrophy in sciatic denervated mice. However, the expressions of HSP70, SOD1, and ceramide in microgravity-exposed C2C12 myoblasts and in sciatic denervated mice were either decreased or completely inhibited. These results suggested that EVP can be expected to have a positive effect on muscle atrophy by disuse and microgravity. In addition, EVP helped characterize the antioxidant function in muscle atrophy.

  10. Claw asymmetry in lobsters: case study in developmental neuroethology.

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    Govind, C K

    1992-12-01

    An enduring debate in the study of development is the relative contribution of genetic and epigenetic factors in the genesis of an organism, that is, the nature vs. nurture debate. The behavior of the paired claws in the lobster offers promising material for pursuing this debate because of the way they develop. The paired claws and their closer muscles are initially symmetrical; both are slender in appearance and have a mixture of fast and slow fibers in their closer muscles. During a critical period of development, they become determined into a major (crusher) and minor (cutter) claw and during subsequent development acquire their final form and behavior: The crusher becomes a stout, molar-toothed claw capable of closing only slowly because its closer muscle has 100% slow fibers while the cutter becomes a slender, incisor-toothed claw capable of closing rapidly because its closer muscle has 90% fast fibers. Our initial hypothesis was that the more active claw became the crusher and its less active counterpart the cutter. Presumably, nerve activity would influence muscle transformation, which in turn would influence the exoskeleton to which they attach and hence claw morphology. Curtailing nerve activity to the claw prevented crusher development, while reflex activation of a claw promoted its development; both results support the notion that nerve activity directly regulates claw form and function. This is not, however, the case, for when both claws were reflexly exercised neither formed a crusher, signifying rather that bilateral differences in predominantly mechanoreceptive input to the paired claws somehow lateralized the claw ganglion [central nervous system (CNS)] into a crusher and cutter side. The side experiencing the greater activity becomes the crusher side while the contralateral side becomes the cutter and is also inhibited from ever becoming a crusher. This initial lateralization in the CNS is expressed, via as yet unknown pathways, at the periphery in

  11. Atomoxetine Prevents Dexamethasone-Induced Skeletal Muscle Atrophy in Mice

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    Jesinkey, Sean R.; Korrapati, Midhun C.; Rasbach, Kyle A.; Beeson, Craig C.

    2014-01-01

    Skeletal muscle atrophy remains a clinical problem in numerous pathologic conditions. β2-Adrenergic receptor agonists, such as formoterol, can induce mitochondrial biogenesis (MB) to prevent such atrophy. Additionally, atomoxetine, an FDA-approved norepinephrine reuptake inhibitor, was positive in a cellular assay for MB. We used a mouse model of dexamethasone-induced skeletal muscle atrophy to investigate the potential role of atomoxetine and formoterol to prevent muscle mass loss. Mice were administered dexamethasone once daily in the presence or absence of formoterol (0.3 mg/kg), atomoxetine (0.1 mg/kg), or sterile saline. Animals were euthanized at 8, 16, and 24 hours or 8 days later. Gastrocnemius muscle weights, changes in mRNA and protein expression of peroxisome proliferator–activated receptor-γ coactivator-1 α (PGC-1α) isoforms, ATP synthase β, cytochrome c oxidase subunit I, NADH dehydrogenase (ubiquinone) 1 β subcomplex, 8, ND1, insulin-like growth factor 1 (IGF-1), myostatin, muscle Ring-finger protein-1 (muscle atrophy), phosphorylated forkhead box protein O 3a (p-FoxO3a), Akt, mammalian target of rapamycin (mTOR), and ribosomal protein S6 (rp-S6; muscle hypertrophy) in naive and muscle-atrophied mice were measured. Atomoxetine increased p-mTOR 24 hours after treatment in naïve mice, but did not change any other biomarkers. Formoterol robustly activated the PGC-1α-4-IGF1–Akt-mTOR-rp-S6 pathway and increased p-FoxO3a as early as 8 hours and repressed myostatin at 16 hours. In contrast to what was observed with acute treatment, chronic treatment (7 days) with atomoxetine increased p-Akt and p-FoxO3a, and sustained PGC-1α expression and skeletal muscle mass in dexamethasone-treated mice, in a manner comparable to formoterol. In conclusion, chronic treatment with a low dose of atomoxetine prevented dexamethasone-induced skeletal muscle wasting and supports a potential role in preventing muscle atrophy. PMID:25292181

  12. Aspiration pneumonia induces muscle atrophy in the respiratory, skeletal, and swallowing systems.

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    Komatsu, Riyo; Okazaki, Tatsuma; Ebihara, Satoru; Kobayashi, Makoto; Tsukita, Yoko; Nihei, Mayumi; Sugiura, Hisatoshi; Niu, Kaijun; Ebihara, Takae; Ichinose, Masakazu

    2018-05-22

    Repetition of the onset of aspiration pneumonia in aged patients is common and causes chronic inflammation. The inflammation induces proinflammatory cytokine production and atrophy in the muscles. The proinflammatory cytokines induce muscle proteolysis by activating calpains and caspase-3, followed by further degradation by the ubiquitin-proteasome system. Autophagy is another pathway of muscle atrophy. However, little is known about the relationship between aspiration pneumonia and muscle. For swallowing muscles, it is not clear whether they produce cytokines. The main objective of this study was to determine whether aspiration pneumonia induces muscle atrophy in the respiratory (the diaphragm), skeletal (the tibialis anterior, TA), and swallowing (the tongue) systems, and their possible mechanisms. We employed a mouse aspiration pneumonia model and computed tomography (CT) scans of aged pneumonia patients. To induce aspiration pneumonia, mice were inoculated with low dose pepsin and lipopolysaccharide solution intra-nasally 5 days a week. The diaphragm, TA, and tongue were isolated, and total RNA, proteins, and frozen sections were stored. Quantitative real-time polymerase chain reaction determined the expression levels of proinflammatory cytokines, muscle E3 ubiquitin ligases, and autophagy related genes. Western blot analysis determined the activation of the muscle proteolysis pathway. Frozen sections determined the presence of muscle atrophy. CT scans were used to evaluate the muscle atrophy in aged aspiration pneumonia patients. The aspiration challenge enhanced the expression levels of proinflammatory cytokines in the diaphragm, TA, and tongue. Among muscle proteolysis pathways, the aspiration challenge activated caspase-3 in all the three muscles examined, whereas calpains were activated in the diaphragm and the TA but not in the tongue. Activation of the ubiquitin-proteasome system was detected in all the three muscles examined. The aspiration challenge

  13. Aging affects the transcriptional regulation of human skeletal muscle disuse atrophy

    DEFF Research Database (Denmark)

    Suetta, Charlotte Arneboe; Frandsen, Ulrik; Jensen, Line

    2012-01-01

    Important insights concerning the molecular basis of skeletal muscle disuse-atrophy and aging related muscle loss have been obtained in cell culture and animal models, but these regulatory signaling pathways have not previously been studied in aging human muscle. In the present study, muscle...... atrophy was induced by immobilization in healthy old and young individuals to study the time-course and transcriptional factors underlying human skeletal muscle atrophy. The results reveal that irrespectively of age, mRNA expression levels of MuRF-1 and Atrogin-1 increased in the very initial phase (2......-4 days) of human disuse-muscle atrophy along with a marked reduction in PGC-1α and PGC-1β (1-4 days) and a ∼10% decrease in myofiber size (4 days). Further, an age-specific decrease in Akt and S6 phosphorylation was observed in young muscle within the first days (1-4 days) of immobilization. In contrast...

  14. Disease-Induced Skeletal Muscle Atrophy and Fatigue

    NARCIS (Netherlands)

    Powers, Scott K.; Lynch, Gordon S.; Murphy, Kate T.; Reid, Michael B.; Zijdewind, Inge

    2016-01-01

    Numerous health problems including acute critical illness, cancer, diseases associated with chronic inflammation, and neurological disorders often result in skeletal muscle weakness and fatigue. Disease-related muscle atrophy and fatigue is an important clinical problem because acquired skeletal

  15. Haptoglobin is required to prevent oxidative stress and muscle atrophy.

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    Enrico Bertaggia

    Full Text Available BACKGROUND: Oxidative stress (OS plays a major role on tissue function. Several catabolic or stress conditions exacerbate OS, inducing organ deterioration. Haptoglobin (Hp is a circulating acute phase protein, produced by liver and adipose tissue, and has an important anti-oxidant function. Hp is induced in pro-oxidative conditions such as systemic inflammation or obesity. The role of systemic factors that modulate oxidative stress inside muscle cells is still poorly investigated. RESULTS: We used Hp knockout mice (Hp-/- to determine the role of this protein and therefore, of systemic OS in maintenance of muscle mass and function. Absence of Hp caused muscle atrophy and weakness due to activation of an atrophy program. When animals were stressed by acute exercise or by high fat diet (HFD, OS, muscle atrophy and force drop were exacerbated in Hp-/-. Depending from the stress condition, autophagy-lysosome and ubiquitin-proteasome systems were differently induced. CONCLUSIONS: Hp is required to prevent OS and the activation of pathways leading to muscle atrophy and weakness in normal condition and upon metabolic challenges.

  16. Muscle atrophy reversed by growth factor activation of satellite cells in a mouse muscle atrophy model.

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    Simon Hauerslev

    Full Text Available Muscular dystrophies comprise a large group of inherited disorders that lead to progressive muscle wasting. We wanted to investigate if targeting satellite cells can enhance muscle regeneration and thus increase muscle mass. We treated mice with hepatocyte growth factor and leukemia inhibitory factor under three conditions: normoxia, hypoxia and during myostatin deficiency. We found that hepatocyte growth factor treatment led to activation of the Akt/mTOR/p70S6K protein synthesis pathway, up-regulation of the myognic transcription factors MyoD and myogenin, and subsequently the negative growth control factor, myostatin and atrophy markers MAFbx and MuRF1. Hypoxia-induced atrophy was partially restored by hepatocyte growth factor combined with leukemia inhibitory factor treatment. Dividing satellite cells were three-fold increased in the treatment group compared to control. Finally, we demonstrated that myostatin regulates satellite cell activation and myogenesis in vivo following treatment, consistent with previous findings in vitro. Our results suggest, not only a novel in vivo pharmacological treatment directed specifically at activating the satellite cells, but also a myostatin dependent mechanism that may contribute to the progressive muscle wasting seen in severely affected patients with muscular dystrophy and significant on-going regeneration. This treatment could potentially be applied to many conditions that feature muscle wasting to increase muscle bulk and strength.

  17. Schisandrae Fructus Supplementation Ameliorates Sciatic Neurectomy-Induced Muscle Atrophy in Mice

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    Joo Wan Kim

    2015-01-01

    Full Text Available The objective of this study was to assess the possible beneficial skeletal muscle preserving effects of ethanol extract of Schisandrae Fructus (EESF on sciatic neurectomy- (NTX- induced hindlimb muscle atrophy in mice. Here, calf muscle atrophy was induced by unilateral right sciatic NTX. In order to investigate whether administration of EESF prevents or improves sciatic NTX-induced muscle atrophy, EESF was administered orally. Our results indicated that EESF dose-dependently diminished the decreases in markers of muscle mass and activity levels, and the increases in markers of muscle damage and fibrosis, inflammatory cell infiltration, cytokines, and apoptotic events in the gastrocnemius muscle bundles are induced by NTX. Additionally, destruction of gastrocnemius antioxidant defense systems after NTX was dose-dependently protected by treatment with EESF. EESF also upregulated muscle-specific mRNAs involved in muscle protein synthesis but downregulated those involved in protein degradation. The overall effects of 500 mg/kg EESF were similar to those of 50 mg/kg oxymetholone, but it showed more favorable antioxidant effects. The present results suggested that EESF exerts a favorable ameliorating effect on muscle atrophy induced by NTX, through anti-inflammatory and antioxidant effects related to muscle fiber protective effects and via an increase in protein synthesis and a decrease in protein degradation.

  18. Schisandrae Fructus Supplementation Ameliorates Sciatic Neurectomy-Induced Muscle Atrophy in Mice

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    Kim, Joo Wan; Ku, Sae-Kwang; Kim, Ki Young; Kim, Sung Goo; Han, Min Ho; Kim, Gi-Young; Hwang, Hye Jin; Kim, Byung Woo; Kim, Cheol Min

    2015-01-01

    The objective of this study was to assess the possible beneficial skeletal muscle preserving effects of ethanol extract of Schisandrae Fructus (EESF) on sciatic neurectomy- (NTX-) induced hindlimb muscle atrophy in mice. Here, calf muscle atrophy was induced by unilateral right sciatic NTX. In order to investigate whether administration of EESF prevents or improves sciatic NTX-induced muscle atrophy, EESF was administered orally. Our results indicated that EESF dose-dependently diminished the decreases in markers of muscle mass and activity levels, and the increases in markers of muscle damage and fibrosis, inflammatory cell infiltration, cytokines, and apoptotic events in the gastrocnemius muscle bundles are induced by NTX. Additionally, destruction of gastrocnemius antioxidant defense systems after NTX was dose-dependently protected by treatment with EESF. EESF also upregulated muscle-specific mRNAs involved in muscle protein synthesis but downregulated those involved in protein degradation. The overall effects of 500 mg/kg EESF were similar to those of 50 mg/kg oxymetholone, but it showed more favorable antioxidant effects. The present results suggested that EESF exerts a favorable ameliorating effect on muscle atrophy induced by NTX, through anti-inflammatory and antioxidant effects related to muscle fiber protective effects and via an increase in protein synthesis and a decrease in protein degradation. PMID:26064425

  19. Notch Signaling Mediates Skeletal Muscle Atrophy in Cancer Cachexia Caused by Osteosarcoma

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    Xiaodong Mu

    2016-01-01

    Full Text Available Skeletal muscle atrophy in cancer cachexia is mediated by the interaction between muscle stem cells and various tumor factors. Although Notch signaling has been known as a key regulator of both cancer development and muscle stem cell activity, the potential involvement of Notch signaling in cancer cachexia and concomitant muscle atrophy has yet to be elucidated. The murine K7M2 osteosarcoma cell line was used to generate an orthotopic model of sarcoma-associated cachexia, and the role of Notch signaling was evaluated. Skeletal muscle atrophy was observed in the sarcoma-bearing mice, and Notch signaling was highly active in both tumor tissues and the atrophic skeletal muscles. Systemic inhibition of Notch signaling reduced muscle atrophy. In vitro coculture of osteosarcoma cells with muscle-derived stem cells (MDSCs isolated from normal mice resulted in decreased myogenic potential of MDSCs, while the application of Notch inhibitor was able to rescue this repressed myogenic potential. We further observed that Notch-activating factors reside in the exosomes of osteosarcoma cells, which activate Notch signaling in MDSCs and subsequently repress myogenesis. Our results revealed that signaling between tumor and muscle via the Notch pathway may play an important role in mediating the skeletal muscle atrophy seen in cancer cachexia.

  20. Molecular events underlying skeletal muscle atrophy and the development of effective countermeasures

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    Booth, F. W.; Criswell, D. S.

    1997-01-01

    Skeletal muscle adapts to loading; atrophying when exposed to unloading on Earth or in spaceflight. Significant atrophy (decreases in muscle fiber cross-section of 11-24%) in humans has been noted after only 5 days in space. Since muscle strength is determined both by muscle cross-section and synchronization of motor unit recruitment, a loss in muscle size weakens astronauts, which would increase risks to their safety if an emergency required maximal muscle force. Numerous countermeasures have been tested to prevent atrophy. Resistant exercise together with growth hormone and IGF-I are effective countermeasures to unloading as most atrophy is prevented in animal models. The loss of muscle protein is due to an early decrease in protein synthesis rate and a later increase in protein degradation. The initial decrease in protein synthesis is a result of decreased protein translation, caused by a prolongation in the elongation rate. A decrease in HSP70 by a sight increase in ATP may be the factors prolonging elongation rate. Increases in the activities of proteolytic enzymes and in ubiquitin contribute to the increased protein degradation rate in unloaded muscle. Numerous mRNA concentrations have been shown to be altered in unloaded muscles. Decreases in mRNAs for contractile proteins usually occur after the initial fall in protein synthesis rates. Much additional research is needed to determine the mechanism by which muscle senses the absence of gravity with an adaptive atrophy. The development of effective countermeasures to unloading atrophy will require more research.

  1. Different atrophy-hypertrophy transcription pathways in muscles affected by severe and mild spinal muscular atrophy

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    Millino Caterina

    2009-04-01

    Full Text Available Abstract Background Spinal muscular atrophy (SMA is a neurodegenerative disorder associated with mutations of the survival motor neuron gene SMN and is characterized by muscle weakness and atrophy caused by degeneration of spinal motor neurons. SMN has a role in neurons but its deficiency may have a direct effect on muscle tissue. Methods We applied microarray and quantitative real-time PCR to study at transcriptional level the effects of a defective SMN gene in skeletal muscles affected by the two forms of SMA: the most severe type I and the mild type III. Results The two forms of SMA generated distinct expression signatures: the SMA III muscle transcriptome is close to that found under normal conditions, whereas in SMA I there is strong alteration of gene expression. Genes implicated in signal transduction were up-regulated in SMA III whereas those of energy metabolism and muscle contraction were consistently down-regulated in SMA I. The expression pattern of gene networks involved in atrophy signaling was completed by qRT-PCR, showing that specific pathways are involved, namely IGF/PI3K/Akt, TNF-α/p38 MAPK and Ras/ERK pathways. Conclusion Our study suggests a different picture of atrophy pathways in each of the two forms of SMA. In particular, p38 may be the regulator of protein synthesis in SMA I. The SMA III profile appears as the result of the concurrent presence of atrophic and hypertrophic fibers. This more favorable condition might be due to the over-expression of MTOR that, given its role in the activation of protein synthesis, could lead to compensatory hypertrophy in SMA III muscle fibers.

  2. The relationship between tear severity, fatty infiltration, and muscle atrophy in the supraspinatus.

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    Barry, Jeffrey J; Lansdown, Drew A; Cheung, Sunny; Feeley, Brian T; Ma, C Benjamin

    2013-01-01

    Fatty infiltration and muscle atrophy have been described as interrelated characteristic changes that occur within the muscles of the rotator cuff after cuff tears, and both are independently associated with poor outcomes after surgical repair. We hypothesize that fatty infiltration and muscle atrophy are two distinct processes independently associated with supraspinatus tears. A retrospective review of 377 patients who underwent shoulder magnetic resonance imaging at one institution was performed. Multivariate analysis was performed based on parameters including age, sex, rotator cuff tear severity, fatty infiltration grade, and muscle atrophy. A total of 116 patients (30.8%) had full-thickness tears of the supraspinatus, 153 (40.6%) had partial thickness tears, and 108 (28.7%) had no evidence of tear. With increasing tear severity, the prevalence of substantial fatty infiltration (grade ≥2) increased: 6.5% of patients with no tears vs 41.4% for complete tears (P tear severity: 36.1% of no tears vs 77.6% of complete tears (P muscle atrophy when taking into account sex, age, and tear severity. Fatty infiltration and muscle atrophy are independently associated processes. Fatty infiltration is also related to increasing age, muscle tear severity, and sex, whereas muscle atrophy is related to increasing age but not tear severity. In patients without rotator cuff tears, fatty infiltration and atrophy prevalence increased independently with increasing age. Copyright © 2013 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.

  3. Inhibition of interleukin-6 decreases atrogene expression and ameliorates tail suspension-induced skeletal muscle atrophy

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    Yakabe, Mitsutaka; Ota, Hidetaka; Iijima, Katsuya; Eto, Masato; Ouchi, Yasuyoshi; Akishita, Masahiro

    2018-01-01

    Background Interleukin-6 (IL-6) is an inflammatory cytokine. Whether systemic IL-6 affects atrogene expression and disuse-induced skeletal muscle atrophy is unclear. Methods Tail-suspended mice were used as a disuse-induced muscle atrophy model. We administered anti-mouse IL-6 receptor antibody, beta-hydroxy-beta-methylbutyrate (HMB) and vitamin D to the mice and examined the effects on atrogene expression and muscle atrophy. Results Serum IL-6 levels were elevated in the mice. Inhibition of IL-6 receptor suppressed muscle RING finger 1 (MuRF1) expression and prevented muscle atrophy. HMB and vitamin D inhibited the serum IL-6 surge, downregulated the expression of MuRF1 and atrogin-1 in the soleus muscle, and ameliorated atrophy in the mice. Conclusion Systemic IL-6 affects MuRF1 expression and disuse-induced muscle atrophy. PMID:29351340

  4. Inhibition of interleukin-6 decreases atrogene expression and ameliorates tail suspension-induced skeletal muscle atrophy.

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    Mitsutaka Yakabe

    Full Text Available Interleukin-6 (IL-6 is an inflammatory cytokine. Whether systemic IL-6 affects atrogene expression and disuse-induced skeletal muscle atrophy is unclear.Tail-suspended mice were used as a disuse-induced muscle atrophy model. We administered anti-mouse IL-6 receptor antibody, beta-hydroxy-beta-methylbutyrate (HMB and vitamin D to the mice and examined the effects on atrogene expression and muscle atrophy.Serum IL-6 levels were elevated in the mice. Inhibition of IL-6 receptor suppressed muscle RING finger 1 (MuRF1 expression and prevented muscle atrophy. HMB and vitamin D inhibited the serum IL-6 surge, downregulated the expression of MuRF1 and atrogin-1 in the soleus muscle, and ameliorated atrophy in the mice.Systemic IL-6 affects MuRF1 expression and disuse-induced muscle atrophy.

  5. Three-Dimensional Culture Model of Skeletal Muscle Tissue with Atrophy Induced by Dexamethasone.

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    Shimizu, Kazunori; Genma, Riho; Gotou, Yuuki; Nagasaka, Sumire; Honda, Hiroyuki

    2017-06-15

    Drug screening systems for muscle atrophy based on the contractile force of cultured skeletal muscle tissues are required for the development of preventive or therapeutic drugs for atrophy. This study aims to develop a muscle atrophy model by inducing atrophy in normal muscle tissues constructed on microdevices capable of measuring the contractile force and to verify if this model is suitable for drug screening using the contractile force as an index. Tissue engineered skeletal muscles containing striated myotubes were prepared on the microdevices for the study. The addition of 100 µM dexamethasone (Dex), which is used as a muscle atrophy inducer, for 24 h reduced the contractile force significantly. An increase in the expression of Atrogin-1 and MuRF-1 in the tissues treated with Dex was established. A decrease in the number of striated myotubes was also observed in the tissues treated with Dex. Treatment with 8 ng/mL Insulin-like Growth Factor (IGF-I) for 24 h significantly increased the contractile force of the Dex-induced atrophic tissues. The same treatment, though, had no impact on the force of the normal tissues. Thus, it is envisaged that the atrophic skeletal muscle tissues induced by Dex can be used for drug screening against atrophy.

  6. Korean mistletoe (Viscum album coloratum) extract regulates gene expression related to muscle atrophy and muscle hypertrophy.

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    Jeong, Juseong; Park, Choon-Ho; Kim, Inbo; Kim, Young-Ho; Yoon, Jae-Min; Kim, Kwang-Soo; Kim, Jong-Bae

    2017-01-21

    Korean mistletoe (Viscum album coloratum) is a semi-parasitic plant that grows on various trees and has a diverse range of effects on biological functions, being implicated in having anti-tumor, immunostimulatory, anti-diabetic, and anti-obesity properties. Recently, we also reported that Korean mistletoe extract (KME) improves endurance exercise in mice, suggesting its beneficial roles in enhancing the capacity of skeletal muscle. We examined the expression pattern of several genes concerned with muscle physiology in C2C12 myotubes cells to identify whether KME inhibits muscle atrophy or promotes muscle hypertrophy. We also investigated these effects of KME in denervated mice model. Interestingly, KME induced the mRNA expression of SREBP-1c, PGC-1α, and GLUT4, known positive regulators of muscle hypertrophy, in C2C12 cells. On the contrary, KME reduced the expression of Atrogin-1, which is directly involved in the induction of muscle atrophy. In animal models, KME mitigated the decrease of muscle weight in denervated mice. The expression of Atrogin-1 was also diminished in those mice. Moreover, KME enhanced the grip strength and muscle weight in long-term feeding mice. Our results suggest that KME has beneficial effects on muscle atrophy and muscle hypertrophy.

  7. New mouse model of skeletal muscle atrophy using spiral wire immobilization.

    Science.gov (United States)

    Onda, Akiko; Kono, Hajime; Jiao, Qibin; Akimoto, Takayuki; Miyamoto, Toshikazu; Sawada, Yasuhiro; Suzuki, Katsuhiko; Kusakari, Yoichiro; Minamisawa, Susumu; Fukubayashi, Toru

    2016-10-01

    Disuse-induced skeletal muscle atrophy is a serious concern; however, there is not an effective mouse model to elucidate the molecular mechanisms. We developed a noninvasive atrophy model in mice. After the ankle joints of mice were bandaged into a bilateral plantar flexed position, either bilateral or unilateral hindlimbs were immobilized by wrapping in bonsai steel wire. After 3, 5, or 10 days of immobilization of the hip, knee, and ankle, the weight of the soleus and plantaris muscles decreased significantly in both bilateral and unilateral immobilization. MAFbx/atrogin-1 and MuRF1 mRNA was found to have significantly increased in both muscles, consistent with disuse-induced atrophy. Notably, the procedure did not result in either edema or necrosis in the fixed hindlimbs. This method allows repeated, direct access to the immobilized muscle, making it a useful procedure for concurrent application and assessment of various therapeutic interventions. Muscle Nerve 54: 788-791, 2016. © 2016 Wiley Periodicals, Inc.

  8. Biomechanical implications of skeletal muscle hypertrophy and atrophy: a musculoskeletal model

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    Andrew D. Vigotsky

    2015-11-01

    Full Text Available Muscle hypertrophy and atrophy occur frequently as a result of mechanical loading or unloading, with implications for clinical, general, and athletic populations. The effects of muscle hypertrophy and atrophy on force production and joint moments have been previously described. However, there is a paucity of research showing how hypertrophy and atrophy may affect moment arm (MA lengths. The purpose of this model was to describe the mathematical relationship between the anatomical cross-sectional area (ACSA of a muscle and its MA length. In the model, the ACSAs of the biceps brachii and brachialis were altered to hypertrophy up to twice their original size and to atrophy to one-half of their original size. The change in MA length was found to be proportional to the arcsine of the square root of the change in ACSA. This change in MA length may be a small but important contributor to strength, especially in sports that require large joint moments at slow joint angular velocities, such as powerlifting. The paradoxical implications of the increase in MA are discussed, as physiological factors influencing muscle contraction velocity appear to favor a smaller MA length for high velocity movements but a larger muscle MA length for low velocity, high force movements.

  9. Extracellular polysaccharides purified from Aureobasidium pullulans SM-2001 (Polycan) inhibit dexamethasone-induced muscle atrophy in mice

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    Cho, Hyung-Rae; Park, Dong-Chan; Jung, Go-Woon

    2018-01-01

    The present study assessed the beneficial skeletal muscle-preserving effects of extracellular polysaccharides from Aureobasidium pullulans SM-2001 (Polycan) (EAP) on dexamethasone (DEXA)-induced catabolic muscle atrophy in mice. To investigate whether EAP prevented catabolic DEXA-induced muscle atrophy, and to examine its mechanisms of action, EAP (100, 200 and 400 mg/kg) was administered orally, once a day for 24 days. EAP treatment was initiated 2 weeks prior to DEXA treatment (1 mg/kg, once a day for 10 days) in mice. Body weight alterations, serum biochemistry, calf thickness, calf muscle strength, gastrocnemius muscle thickness and weight, gastrocnemius muscle antioxidant defense parameters, gastrocnemius muscle mRNA expression, histology and histomorphometry were subsequently assessed. After 24 days, DEXA control mice exhibited muscle atrophy according to all criteria indices. However, these muscle atrophy symptoms were significantly inhibited by oral treatment with all three doses of EAP. Regarding possible mechanisms of action, EAP exhibited favorable ameliorating effects on DEXA-induced catabolic muscle atrophy via antioxidant and anti-inflammatory effects; these effects were mediated by modulation of the expression of genes involved in muscle protein synthesis (AKT serine/threonine kinase 1, phosphatidylinositol 3-kinase, adenosine A1 receptor and transient receptor potential cation channel subfamily V member 4) and degradation (atrogin-1, muscle RING-finger protein-1, myostatin and sirtuin 1). Therefore, these results indicated that EAP may be helpful in improving muscle atrophies of various etiologies. EAP at 400 mg/kg exhibited favorable muscle protective effects against DEXA-induced catabolic muscle atrophy, comparable with the effects of oxymetholone (50 mg/kg), which has been used to treat various muscle disorders. PMID:29138805

  10. Mechanisms of cisplatin-induced muscle atrophy

    International Nuclear Information System (INIS)

    Sakai, Hiroyasu; Sagara, Atsunobu; Arakawa, Kazuhiko; Sugiyama, Ryoto; Hirosaki, Akiko; Takase, Kazuhide; Jo, Ara; Sato, Ken; Chiba, Yoshihiko; Yamazaki, Mitsuaki; Matoba, Motohiro; Narita, Minoru

    2014-01-01

    Fatigue is the most common side effect of chemotherapy. However, the mechanisms of “muscle fatigue” induced by anti-cancer drugs are not fully understood. We therefore investigated the muscle-atrophic effect of cisplatin, a platinum-based anti-cancer drug, in mice. C57BL/6J mice were treated with cisplatin (3 mg/kg, i.p.) or saline for 4 consecutive days. On Day 5, hindlimb and quadriceps muscles were isolated from mice. The loss of body weight and food intake under the administration of cisplatin was the same as those in a dietary restriction (DR) group. Under the present conditions, the administration of cisplatin significantly decreased not only the muscle mass of the hindlimb and quadriceps but also the myofiber diameter, compared to those in the DR group. The mRNA expression levels of muscle atrophy F-box (MAFbx), muscle RING finger-1 (MuRF1) and forkhead box O3 (FOXO3) were significantly and further increased by cisplatin treated group, compared to DR. Furthermore, the mRNA levels of myostatin and p21 were significantly upregulated by the administration of cisplatin, compared to DR. On the other hand, the phosphorylation of Akt and FOXO3a, which leads to the blockade of the upregulation of MuRF1 and MAFbx, was significantly and dramatically decreased by cisplatin. These findings suggest that the administration of cisplatin increases atrophic gene expression, and may lead to an imbalance between protein synthesis and protein degradation pathways, which would lead to muscle atrophy. This phenomenon could, at least in part, explain the mechanism of cisplatin-induced muscle fatigue. - Highlights: • Cisplatin decreased mass and myofiber diameter in quadriceps muscle. • The mRNA of MAFbx, MuRF1 and FOXO3 were increased by the cisplatin. • The mRNA of myostatin and p21 were upregulated by cisplatin. • The phosphorylation of Akt and FOXO3a was decreased by cisplatin

  11. Mechanisms of cisplatin-induced muscle atrophy

    Energy Technology Data Exchange (ETDEWEB)

    Sakai, Hiroyasu, E-mail: sakai@hoshi.ac.jp [Department of Pharmacology, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 1428501 (Japan); Division of Pharmacy Professional Development and Research, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 1428501 (Japan); Sagara, Atsunobu; Arakawa, Kazuhiko; Sugiyama, Ryoto; Hirosaki, Akiko; Takase, Kazuhide; Jo, Ara [Department of Pharmacology, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 1428501 (Japan); Sato, Ken [Department of Pharmacology, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 1428501 (Japan); Division of Pharmacy Professional Development and Research, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 1428501 (Japan); Chiba, Yoshihiko [Department of Biology, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 1428501 (Japan); Yamazaki, Mitsuaki [Department of Anesthesiology, Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, 2630 Sugitani, Toyama-shi, Toyama 9300194 (Japan); Matoba, Motohiro [Department of Palliative Medicine and Psychooncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 1040045 (Japan); Narita, Minoru, E-mail: narita@hoshi.ac.jp [Department of Pharmacology, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 1428501 (Japan)

    2014-07-15

    Fatigue is the most common side effect of chemotherapy. However, the mechanisms of “muscle fatigue” induced by anti-cancer drugs are not fully understood. We therefore investigated the muscle-atrophic effect of cisplatin, a platinum-based anti-cancer drug, in mice. C57BL/6J mice were treated with cisplatin (3 mg/kg, i.p.) or saline for 4 consecutive days. On Day 5, hindlimb and quadriceps muscles were isolated from mice. The loss of body weight and food intake under the administration of cisplatin was the same as those in a dietary restriction (DR) group. Under the present conditions, the administration of cisplatin significantly decreased not only the muscle mass of the hindlimb and quadriceps but also the myofiber diameter, compared to those in the DR group. The mRNA expression levels of muscle atrophy F-box (MAFbx), muscle RING finger-1 (MuRF1) and forkhead box O3 (FOXO3) were significantly and further increased by cisplatin treated group, compared to DR. Furthermore, the mRNA levels of myostatin and p21 were significantly upregulated by the administration of cisplatin, compared to DR. On the other hand, the phosphorylation of Akt and FOXO3a, which leads to the blockade of the upregulation of MuRF1 and MAFbx, was significantly and dramatically decreased by cisplatin. These findings suggest that the administration of cisplatin increases atrophic gene expression, and may lead to an imbalance between protein synthesis and protein degradation pathways, which would lead to muscle atrophy. This phenomenon could, at least in part, explain the mechanism of cisplatin-induced muscle fatigue. - Highlights: • Cisplatin decreased mass and myofiber diameter in quadriceps muscle. • The mRNA of MAFbx, MuRF1 and FOXO3 were increased by the cisplatin. • The mRNA of myostatin and p21 were upregulated by cisplatin. • The phosphorylation of Akt and FOXO3a was decreased by cisplatin.

  12. Differential response of skeletal muscles to mTORC1 signaling during atrophy and hypertrophy

    Science.gov (United States)

    2013-01-01

    Background Skeletal muscle mass is determined by the balance between protein synthesis and degradation. Mammalian target of rapamycin complex 1 (mTORC1) is a master regulator of protein translation and has been implicated in the control of muscle mass. Inactivation of mTORC1 by skeletal muscle-specific deletion of its obligatory component raptor results in smaller muscles and a lethal dystrophy. Moreover, raptor-deficient muscles are less oxidative through changes in the expression PGC-1α, a critical determinant of mitochondrial biogenesis. These results suggest that activation of mTORC1 might be beneficial to skeletal muscle by providing resistance to muscle atrophy and increasing oxidative function. Here, we tested this hypothesis by deletion of the mTORC1 inhibitor tuberous sclerosis complex (TSC) in muscle fibers. Method Skeletal muscles of mice with an acute or a permanent deletion of raptor or TSC1 were examined using histological, biochemical and molecular biological methods. Response of the muscles to changes in mechanical load and nerve input was investigated by ablation of synergistic muscles or by denervation . Results Genetic deletion or knockdown of raptor, causing inactivation of mTORC1, was sufficient to prevent muscle growth and enhance muscle atrophy. Conversely, short-term activation of mTORC1 by knockdown of TSC induced muscle fiber hypertrophy and atrophy-resistance upon denervation, in both fast tibialis anterior (TA) and slow soleus muscles. Surprisingly, however, sustained activation of mTORC1 by genetic deletion of Tsc1 caused muscle atrophy in all but soleus muscles. In contrast, oxidative capacity was increased in all muscles examined. Consistently, TSC1-deficient soleus muscle was atrophy-resistant whereas TA underwent normal atrophy upon denervation. Moreover, upon overloading, plantaris muscle did not display enhanced hypertrophy compared to controls. Biochemical analysis indicated that the atrophy response of muscles was based on the

  13. The quasi-parallel lives of satellite cells and atrophying muscle

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    Stefano eBiressi

    2015-07-01

    Full Text Available Skeletal muscle atrophy or wasting accompanies various chronic illnesses and the aging process, thereby reducing muscle function. One of the most important components contributing to effective muscle repair in postnatal organisms, the satellite cells, have recently become the focus of several studies examining factors participating in the atrophic process. We critically examine here the experimental evidence linking satellite cell function with muscle loss in connection with various diseases as well as aging, and in the subsequent recovery process. Several recent reports have investigated the changes in satellite cells in terms of their differentiation and proliferative capacity in response to various atrophic stimuli. In this regard, we review the molecular changes within satellite cells that contribute to their dysfunctional status in atrophy, with the intention of shedding light on novel potential pharmacological targets to counteract the loss of muscle mass.

  14. p53 and ATF4 mediate distinct and additive pathways to skeletal muscle atrophy during limb immobilization

    Science.gov (United States)

    Fox, Daniel K.; Ebert, Scott M.; Bongers, Kale S.; Dyle, Michael C.; Bullard, Steven A.; Dierdorff, Jason M.; Kunkel, Steven D.

    2014-01-01

    Immobilization causes skeletal muscle atrophy via complex signaling pathways that are not well understood. To better understand these pathways, we investigated the roles of p53 and ATF4, two transcription factors that mediate adaptations to a variety of cellular stresses. Using mouse models, we demonstrate that 3 days of muscle immobilization induces muscle atrophy and increases expression of p53 and ATF4. Furthermore, muscle fibers lacking p53 or ATF4 are partially resistant to immobilization-induced muscle atrophy, and forced expression of p53 or ATF4 induces muscle fiber atrophy in the absence of immobilization. Importantly, however, p53 and ATF4 do not require each other to promote atrophy, and coexpression of p53 and ATF4 induces more atrophy than either transcription factor alone. Moreover, muscle fibers lacking both p53 and ATF4 are more resistant to immobilization-induced atrophy than fibers lacking only p53 or ATF4. Interestingly, the independent and additive nature of the p53 and ATF4 pathways allows for combinatorial control of at least one downstream effector, p21. Using genome-wide mRNA expression arrays, we identified p21 mRNA as a skeletal muscle transcript that is highly induced in immobilized muscle via the combined actions of p53 and ATF4. Additionally, in mouse muscle, p21 induces atrophy in a manner that does not require immobilization, p53 or ATF4, and p21 is required for atrophy induced by immobilization, p53, and ATF4. Collectively, these results identify p53 and ATF4 as essential and complementary mediators of immobilization-induced muscle atrophy and discover p21 as a critical downstream effector of the p53 and ATF4 pathways. PMID:24895282

  15. Protective Effects of Clenbuterol against Dexamethasone-Induced Masseter Muscle Atrophy and Myosin Heavy Chain Transition.

    Directory of Open Access Journals (Sweden)

    Daisuke Umeki

    Full Text Available Glucocorticoid has a direct catabolic effect on skeletal muscle, leading to muscle atrophy, but no effective pharmacotherapy is available. We reported that clenbuterol (CB induced masseter muscle hypertrophy and slow-to-fast myosin heavy chain (MHC isoform transition through direct muscle β2-adrenergic receptor stimulation. Thus, we hypothesized that CB would antagonize glucocorticoid (dexamethasone; DEX-induced muscle atrophy and fast-to-slow MHC isoform transition.We examined the effect of CB on DEX-induced masseter muscle atrophy by measuring masseter muscle weight, fiber diameter, cross-sectional area, and myosin heavy chain (MHC composition. To elucidate the mechanisms involved, we used immunoblotting to study the effects of CB on muscle hypertrophic signaling (insulin growth factor 1 (IGF1 expression, Akt/mammalian target of rapamycin (mTOR pathway, and calcineurin pathway and atrophic signaling (Akt/Forkhead box-O (FOXO pathway and myostatin expression in masseter muscle of rats treated with DEX and/or CB.Masseter muscle weight in the DEX-treated group was significantly lower than that in the Control group, as expected, but co-treatment with CB suppressed the DEX-induced masseter muscle atrophy, concomitantly with inhibition of fast-to-slow MHC isoforms transition. Activation of the Akt/mTOR pathway in masseter muscle of the DEX-treated group was significantly inhibited compared to that of the Control group, and CB suppressed this inhibition. DEX also suppressed expression of IGF1 (positive regulator of muscle growth, and CB attenuated this inhibition. Myostatin protein expression was unchanged. CB had no effect on activation of the Akt/FOXO pathway. These results indicate that CB antagonizes DEX-induced muscle atrophy and fast-to-slow MHC isoform transition via modulation of Akt/mTOR activity and IGF1 expression. CB might be a useful pharmacological agent for treatment of glucocorticoid-induced muscle atrophy.

  16. Curcumin ameliorates skeletal muscle atrophy in type 1 diabetic mice by inhibiting protein ubiquitination.

    Science.gov (United States)

    Ono, Taisuke; Takada, Shingo; Kinugawa, Shintaro; Tsutsui, Hiroyuki

    2015-09-01

    What is the central question of this study? We sought to examine whether curcumin could ameliorate skeletal muscle atrophy in diabetic mice by inhibiting protein ubiquitination, inflammatory cytokines and oxidative stress. What is the main finding and its importance? We found that curcumin ameliorated skeletal muscle atrophy in streptozotocin-induced diabetic mice by inhibiting protein ubiquitination without affecting protein synthesis. This favourable effect of curcumin was possibly due to the inhibition of inflammatory cytokines and oxidative stress. Curcumin may be beneficial for the treatment of muscle atrophy in type 1 diabetes mellitus. Skeletal muscle atrophy develops in patients with diabetes mellitus (DM), especially in type 1 DM, which is associated with chronic inflammation. Curcumin, the active ingredient of turmeric, has various biological actions, including anti-inflammatory and antioxidant properties. We hypothesized that curcumin could ameliorate skeletal muscle atrophy in mice with streptozotocin-induced type 1 DM. C57BL/6 J mice were injected with streptozotocin (200 mg kg(-1) i.p.; DM group) or vehicle (control group). Each group of mice was randomly subdivided into two groups of 10 mice each and fed a diet with or without curcumin (1500 mg kg(-1) day(-1)) for 2 weeks. There were significant decreases in body weight, skeletal muscle weight and cellular cross-sectional area of the skeletal muscle in DM mice compared with control mice, and these changes were significantly attenuated in DM+Curcumin mice without affecting plasma glucose and insulin concentrations. Ubiquitination of protein was increased in skeletal muscle from DM mice and decreased in DM+Curcumin mice. Gene expressions of muscle-specific ubiquitin E3 ligase atrogin-1/MAFbx and MuRF1 were increased in DM and inhibited in DM+Curcumin mice. Moreover, nuclear factor-κB activation, concentrations of the inflammatory cytokines tumour necrosis factor-α and interleukin-1β and oxidative

  17. CT findings of cervical spondylosis associated with muscle atrophy in the upper extremity

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    Torigoe, Yasuyuki [Okayama Univ. (Japan). School of Medicine

    1995-11-01

    The shape, site and size of osteophytes in cervical spondylosis associated with muscle atrophy were studied by CT to know their relation with pathogenesis. Subjects were: muscle atrophy group (30 cases, 59.5-year-old in a mean, operation was performed on 26), spondylosis group (20, 60.0 year-old) and normal group (10, 60.2-year-old). Their cervical vertebral regions were subjected to the scout roentgenography, CT and myelography. Osteophytes were measured on the x-ray film copied from CT-monitoring image. In the muscle atrophy group, about the shape around vertebral foramen, the occipitofrontal diameter of vertebral canal was found larger than in spondylosis group. Osteophytes were often localized at the outer position of paramedian site, of which constriction was rather smaller. The shape of the vertebral arch was keen. Clinically, the muscle atrophy group was considered to be of myelosis under such conditions as having less affective lesion on spinal cord. (H.O.)

  18. Soy Glycinin Contains a Functional Inhibitory Sequence against Muscle-Atrophy-Associated Ubiquitin Ligase Cbl-b

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    Tomoki Abe

    2013-01-01

    Full Text Available Background. Unloading stress induces skeletal muscle atrophy. We have reported that Cbl-b ubiquitin ligase is a master regulator of unloading-associated muscle atrophy. The present study was designed to elucidate whether dietary soy glycinin protein prevents denervation-mediated muscle atrophy, based on the presence of inhibitory peptides against Cbl-b ubiquitin ligase in soy glycinin protein. Methods. Mice were fed either 20% casein diet, 20% soy protein isolate diet, 10% glycinin diet containing 10% casein, or 20% glycinin diet. One week later, the right sciatic nerve was cut. The wet weight, cross sectional area (CSA, IGF-1 signaling, and atrogene expression in hindlimb muscles were examined at 1, 3, 3.5, or 4 days after denervation. Results. 20% soy glycinin diet significantly prevented denervation-induced decreases in muscle wet weight and myofiber CSA. Furthermore, dietary soy protein inhibited denervation-induced ubiquitination and degradation of IRS-1 in tibialis anterior muscle. Dietary soy glycinin partially suppressed the denervation-mediated expression of atrogenes, such as MAFbx/atrogin-1 and MuRF-1, through the protection of IGF-1 signaling estimated by phosphorylation of Akt-1. Conclusions. Soy glycinin contains a functional inhibitory sequence against muscle-atrophy-associated ubiquitin ligase Cbl-b. Dietary soy glycinin protein significantly prevented muscle atrophy after denervation in mice.

  19. Petri net-based prediction of therapeutic targets that recover abnormally phosphorylated proteins in muscle atrophy.

    Science.gov (United States)

    Jung, Jinmyung; Kwon, Mijin; Bae, Sunghwa; Yim, Soorin; Lee, Doheon

    2018-03-05

    Muscle atrophy, an involuntary loss of muscle mass, is involved in various diseases and sometimes leads to mortality. However, therapeutics for muscle atrophy thus far have had limited effects. Here, we present a new approach for therapeutic target prediction using Petri net simulation of the status of phosphorylation, with a reasonable assumption that the recovery of abnormally phosphorylated proteins can be a treatment for muscle atrophy. The Petri net model was employed to simulate phosphorylation status in three states, i.e. reference, atrophic and each gene-inhibited state based on the myocyte-specific phosphorylation network. Here, we newly devised a phosphorylation specific Petri net that involves two types of transitions (phosphorylation or de-phosphorylation) and two types of places (activation with or without phosphorylation). Before predicting therapeutic targets, the simulation results in reference and atrophic states were validated by Western blotting experiments detecting five marker proteins, i.e. RELA, SMAD2, SMAD3, FOXO1 and FOXO3. Finally, we determined 37 potential therapeutic targets whose inhibition recovers the phosphorylation status from an atrophic state as indicated by the five validated marker proteins. In the evaluation, we confirmed that the 37 potential targets were enriched for muscle atrophy-related terms such as actin and muscle contraction processes, and they were also significantly overlapping with the genes associated with muscle atrophy reported in the Comparative Toxicogenomics Database (p-value net. We generated a list of the potential therapeutic targets whose inhibition recovers abnormally phosphorylated proteins in an atrophic state. They were evaluated by various approaches, such as Western blotting, GO terms, literature, known muscle atrophy-related genes and shortest path analysis. We expect the new proposed strategy to provide an understanding of phosphorylation status in muscle atrophy and to provide assistance towards

  20. Cancer cachexia-induced muscle atrophy: evidence for alterations in microRNAs important for muscle size.

    Science.gov (United States)

    Lee, David E; Brown, Jacob L; Rosa-Caldwell, Megan E; Blackwell, Thomas A; Perry, Richard A; Brown, Lemuel A; Khatri, Bhuwan; Seo, Dongwon; Bottje, Walter G; Washington, Tyrone A; Wiggs, Michael P; Kong, Byung-Whi; Greene, Nicholas P

    2017-05-01

    Muscle atrophy is a hallmark of cancer cachexia resulting in impaired function and quality of life and cachexia is the immediate cause of death for 20-40% of cancer patients. Multiple microRNAs (miRNAs) have been identified as being involved in muscle development and atrophy; however, less is known specifically on miRNAs in cancer cachexia. The purpose of this investigation was to examine the miRNA profile of skeletal muscle atrophy induced by cancer cachexia to uncover potential miRNAs involved with this catabolic condition. Phosphate-buffered saline (PBS) or Lewis lung carcinoma cells (LLC) were injected into C57BL/6J mice at 8 wk of age. LLC animals were allowed to develop tumors for 4 wk to induce cachexia. Tibialis anterior muscles were extracted and processed to isolate small RNAs, which were used for miRNA sequencing. Sequencing results were assembled with mature miRNAs, and functions of miRNAs were analyzed by Ingenuity Pathway Analysis. LLC animals developed tumors that contributed to significantly smaller tibialis anterior muscles (18.5%) and muscle cross-sectional area (40%) compared with PBS. We found 371 miRNAs to be present in the muscle above background levels. Of these, nine miRNAs were found to be differentially expressed. Significantly altered groups of miRNAs were categorized into primary functionalities including cancer, cell-to-cell signaling, and cellular development among others. Gene network analysis predicted specific alterations of factors contributing to muscle size including Akt, FOXO3, and others. These results create a foundation for future research into the sufficiency of targeting these genes to attenuate muscle loss in cancer cachexia. Copyright © 2017 the American Physiological Society.

  1. Is the Supraspinatus Muscle Atrophy Truly Irreversible after Surgical Repair of Rotator Cuff Tears?

    Science.gov (United States)

    Chung, Seok Won; Kim, Sae Hoon; Tae, Suk-Kee; Yoon, Jong Pil; Choi, Jung-Ah

    2013-01-01

    Background Atrophy of rotator cuff muscles has been considered an irreversible phenomenon. The purpose of this study is to evaluate whether atrophy is truly irreversible after rotator cuff repair. Methods We measured supraspinatus muscle atrophy of 191 patients with full-thickness rotator cuff tears on preoperative magnetic resonance imaging and postoperative multidetector computed tomography images, taken at least 1 year after operation. The occupation ratio was calculated using Photoshop CS3 software. We compared the change between pre- and postoperative occupation ratios after modifying the preoperative occupation ratio. In addition, possible relationship between various clinical factors and the change of atrophy, and between the change of atrophy and cuff integrity after surgical repair were evaluated. Results The mean occupation ratio was significantly increased postoperatively from 0.44 ± 0.17 to 0.52 ± 0.17 (p < 0.001). Among 191 patients, 81 (42.4%) showed improvement of atrophy (more than a 10% increase in occupation ratio) and 33 (17.3%) worsening (more than a 10% decrease). Various clinical factors such as age tear size, or initial degree of atrophy did not affect the change of atrophy. However, the change of atrophy was related to repair integrity: cuff healing failure rate of 48.5% (16 of 33) in worsened atrophy; and 22.2% (18 of 81) in improved atrophy (p = 0.007). Conclusions The supraspinatus muscle atrophy as measured by occupation ratio could be improved postoperatively in case of successful cuff repair. PMID:23467404

  2. Molecular mechanisms of muscle atrophy in myotonic dystrophies

    OpenAIRE

    Timchenko, Lubov

    2013-01-01

    Myotonic dystrophy type 1 (DM1) and myotonic dystrophy type 2 (DM2) are multisystemic diseases that primarily affect skeletal muscle, causing myotonia, muscle atrophy, and muscle weakness. DM1 and DM2 pathologies are caused by expansion of CTG and CCTG repeats in non-coding regions of the genes encoding myotonic dystrophy protein kinase (DMPK) and Zinc finger protein 9 (ZNF9) respectively. These expansions cause DM pathologies through accumulation of mutant RNAs that alter RNA metabolism in p...

  3. Skeletal muscle mass recovery from atrophy in IL-6 knockout mice.

    Science.gov (United States)

    Washington, T A; White, J P; Davis, J M; Wilson, L B; Lowe, L L; Sato, S; Carson, J A

    2011-08-01

    Skeletal muscle interleukin-6 (IL-6) expression is induced by continuous contraction, overload-induced hypertrophy and during muscle regeneration. The loss of IL-6 can alter skeletal muscle's growth and extracellular matrix remodelling response to overload-induced hypertrophy. Insulin-like growth factor-1 (IGF-1) gene expression and related signalling through Akt/mTOR is a critical regulator of muscle mass. The significance of IL-6 expression during the recovery from muscle atrophy is unclear. This study's purpose was to determine the effect of IL-6 loss on mouse gastrocnemius (GAS) muscle mass during recovery from hindlimb suspension (HS)-induced atrophy. Female C57BL/6 [wild type (WT)] and IL-6 knockout (IL-6 KO) mice at 10 weeks of age were assigned to control, HS or HS followed by normal cage ambulation groups. GAS muscle atrophy was induced by 10 days of HS. HS induced a 20% loss of GAS mass in both WT and IL-6 KO mice. HS+7 days of recovery restored WT GAS mass to cage-control values. GAS mass from IL-6 KO mice did not return to cage-control values until HS+14 days of recovery. Both IGF-1 mRNA expression and Akt/mTOR signalling were increased in WT muscle after 1 day of recovery. In IL-6 KO muscle, IGF-1 mRNA expression was decreased and Akt/mTOR signalling was not induced after 1 day of recovery. MyoD and myogenin mRNA expression were both induced in WT muscle after 1 day of recovery, but not in IL-6 KO muscle.   Muscle IL-6 expression appears important for the initial growth response during the recovery from disuse. © 2011 The Authors. Acta Physiologica © 2011 Scandinavian Physiological Society.

  4. β–Hydroxy β–Methylbutyrate Improves Dexamethasone-Induced Muscle Atrophy by Modulating the Muscle Degradation Pathway in SD Rat

    Science.gov (United States)

    Choi, Yeon Ja; Park, Min Hi; Jang, Eun Ji; Park, Chan Hum; Yoon, Changshin; Kim, Nam Deuk; Kim, Mi Kyung; Chung, Hae Young

    2014-01-01

    Skeletal muscle atrophy results from various conditions including high levels of glucocorticoids, and β–hydroxy β–methylbutyrate (HMB; a metabolite of leucine) is a potent therapeutical supplement used to treat various muscle disorders. Recent studies have demonstrated that HMB inhibits dexamethasone-induced atrophy in cultured myotubes, but its effect on dexamethasone-induced muscle atrophy has not been determined in vivo. In the present study, we investigated the effect of HMB on dexamethasone-induced muscle atrophy in rats. Treatment with dexamethasone weakened grip strengths and increased muscle damage as determined by increased serum creatine kinase levels and by histological analysis. Dexamethasone treatment also reduced both soleus and gastrocnemius muscle masses. However, HMB supplementation significantly prevented reductions in grip strengths, reduced muscle damage, and prevented muscle mass and protein concentration decrease in soleus muscle. Biochemical analysis demonstrated that dexamethasone markedly increased levels of MuRF1 protein, which causes the ubiquitination and degradation of MyHC. Indeed, dexamethasone treatment decreased MyHC protein expression and increased the ubiquitinated-MyHC to MyHC ratio. However, HMB supplementation caused the down-regulations of MuRF1 protein and of ubiquitinated-MyHC. Furthermore, additional experiments provided evidence that HMB supplementation inhibited the nuclear translocation of FOXO1 induced by dexamethasone, and showed increased MyoD expression in the nuclear fractions of soleus muscles. These findings suggest that HMB supplementation attenuates dexamethasone-induced muscle wasting by regulating FOXO1 transcription factor and subsequent MuRF1 expression. Accordingly, our results suggest that HMB supplementation could be used to prevent steroid myopathy. PMID:25032690

  5. Dynamic changes in the mouse skeletal muscle proteome during denervation-induced atrophy

    Directory of Open Access Journals (Sweden)

    Franziska Lang

    2017-07-01

    Full Text Available Loss of neuronal stimulation enhances protein breakdown and reduces protein synthesis, causing rapid loss of muscle mass. To elucidate the pathophysiological adaptations that occur in atrophying muscles, we used stable isotope labelling and mass spectrometry to quantify protein expression changes accurately during denervation-induced atrophy after sciatic nerve section in the mouse gastrocnemius muscle. Additionally, mice were fed a stable isotope labelling of amino acids in cell culture (SILAC diet containing 13C6-lysine for 4, 7 or 11 days to calculate relative levels of protein synthesis in denervated and control muscles. Ubiquitin remnant peptides (K-ε-GG were profiled by immunoaffinity enrichment to identify potential substrates of the ubiquitin-proteasomal pathway. Of the 4279 skeletal muscle proteins quantified, 850 were differentially expressed significantly within 2 weeks after denervation compared with control muscles. Moreover, pulse labelling identified Lys6 incorporation in 4786 proteins, of which 43 had differential Lys6 incorporation between control and denervated muscle. Enrichment of diglycine remnants identified 2100 endogenous ubiquitination sites and revealed a metabolic and myofibrillar protein diglycine signature, including myosin heavy chains, myomesins and titin, during denervation. Comparative analysis of these proteomic data sets with known atrogenes using a random forest approach identified 92 proteins subject to atrogene-like regulation that have not previously been associated directly with denervation-induced atrophy. Comparison of protein synthesis and proteomic data indicated that upregulation of specific proteins in response to denervation is mainly achieved by protein stabilization. This study provides the first integrated analysis of protein expression, synthesis and ubiquitin signatures during muscular atrophy in a living animal.

  6. Taurine Rescues Cisplatin-Induced Muscle Atrophy In Vitro: A Morphological Study

    Directory of Open Access Journals (Sweden)

    Alessandra Stacchiotti

    2014-01-01

    Full Text Available Cisplatin (CisPt is a widely used chemotherapeutic drug whose side effects include muscle weakness and cachexia. Here we analysed CisPt-induced atrophy in C2C12 myotubes by a multidisciplinary morphological approach, focusing on the onset and progression of autophagy, a protective cellular process that, when excessively activated, may trigger protein hypercatabolism and atrophy in skeletal muscle. To visualize autophagy we used confocal and transmission electron microscopy at different times of treatment and doses of CisPt. Moreover we evaluated the effects of taurine, a cytoprotective beta-amino acid able to counteract oxidative stress, apoptosis, and endoplasmic reticulum stress in different tissues and organs. Our microscopic results indicate that autophagy occurs very early in 50 μM CisPt challenged myotubes (4 h–8 h before overt atrophy but it persists even at 24 h, when several autophagic vesicles, damaged mitochondria, and sarcoplasmic blebbings engulf the sarcoplasm. Differently, 25 mM taurine pretreatment rescues the majority of myotubes size upon 50 μM CisPt at 24 h. Taurine appears to counteract atrophy by restoring regular microtubular apparatus and mitochondria and reducing the overload and the localization of autophagolysosomes. Such a promising taurine action in preventing atrophy needs further molecular and biochemical studies to best define its impact on muscle homeostasis and the maintenance of an adequate skeletal mass in vivo.

  7. Myostatin propeptide gene delivery by gene gun ameliorates muscle atrophy in a rat model of botulinum toxin-induced nerve denervation.

    Science.gov (United States)

    Tsai, Sen-Wei; Tung, Yu-Tang; Chen, Hsiao-Ling; Yang, Shang-Hsun; Liu, Chia-Yi; Lu, Michelle; Pai, Hui-Jing; Lin, Chi-Chen; Chen, Chuan-Mu

    2016-02-01

    Muscle atrophy is a common symptom after nerve denervation. Myostatin propeptide, a precursor of myostatin, has been documented to improve muscle growth. However, the mechanism underlying the muscle atrophy attenuation effects of myostatin propeptide in muscles and the changes in gene expression are not well established. We investigated the possible underlying mechanisms associated with myostatin propeptide gene delivery by gene gun in a rat denervation muscle atrophy model, and evaluated gene expression patterns. In a rat botulinum toxin-induced nerve denervation muscle atrophy model, we evaluated the effects of wild-type (MSPP) and mutant-type (MSPPD75A) of myostatin propeptide gene delivery, and observed changes in gene activation associated with the neuromuscular junction, muscle and nerve. Muscle mass and muscle fiber size was moderately increased in myostatin propeptide treated muscles (pmyostatin propeptide gene delivery, especially the mutant-type of MSPPD75A, attenuates muscle atrophy through myogenic regulatory factors and acetylcholine receptor regulation. Our data concluded that myostatin propeptide gene therapy may be a promising treatment for nerve denervation induced muscle atrophy. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Prevalence and pattern of gluteus medius and minimus tendon pathology and muscle atrophy in older individuals using MRI

    Energy Technology Data Exchange (ETDEWEB)

    Chi, Andrew S. [University of Pennsylvania, Department of Radiology, Philadelphia, PA (United States); Long, Suzanne S.; Zoga, Adam C.; Read, Paul J.; Deely, Diane M.; Parker, Laurence; Morrison, William B. [Thomas Jefferson University Hospital, Department of Radiology, Philadelphia, PA (United States)

    2015-12-15

    To evaluate gluteus medius and minimus tendon pathology and muscle atrophy in older individuals using MRI. A retrospective MRI study of 185 individuals was performed. The inclusion criterion was age ≥50. Exclusion criteria were hip surgery, fracture, infection, tumor, or inadequate image quality. Greater trochanteric bursitis was graded none, mild, moderate, or severe. Gluteus medius, gluteus minimus, and iliopsoas tendinopathy was graded normal, tendinosis, low-grade partial tear, high-grade partial tear, or full thickness tear. Gluteus medius, gluteus minimus, tensor fascia lata, and iliopsoas muscle atrophy was scored using a standard scale. Insertion site of tendinopathy and location of muscle atrophy were assessed. Descriptive and statistical analysis was performed. There was increasing greater trochanteric bursitis and gluteus medius and minimus tendinopathy and atrophy with advancing age with moderate to strong positive associations (p < 0.0001) for age and tendinopathy, age and atrophy, bursitis and tendinopathy, and tendinopathy and atrophy for the gluteus medius and minimus. There is a weak positive association (p < 0.0001) for age and tensor fascia lata atrophy, and no statistically significant association between age and tendinopathy or between age and atrophy for the iliopsoas. Fisher's exact tests were statistically significant (p < 0.0001) for insertion site of tendon pathology and location of muscle atrophy for the gluteus medius. Gluteus medius and minimus tendon pathology and muscle atrophy increase with advancing age with progression of tendinosis to low-grade tendon tears to high-grade tendon tears. There is an associated progression in atrophy of these muscles, which may be important in fall-related hip fractures. (orig.)

  9. Prevalence and pattern of gluteus medius and minimus tendon pathology and muscle atrophy in older individuals using MRI

    International Nuclear Information System (INIS)

    Chi, Andrew S.; Long, Suzanne S.; Zoga, Adam C.; Read, Paul J.; Deely, Diane M.; Parker, Laurence; Morrison, William B.

    2015-01-01

    To evaluate gluteus medius and minimus tendon pathology and muscle atrophy in older individuals using MRI. A retrospective MRI study of 185 individuals was performed. The inclusion criterion was age ≥50. Exclusion criteria were hip surgery, fracture, infection, tumor, or inadequate image quality. Greater trochanteric bursitis was graded none, mild, moderate, or severe. Gluteus medius, gluteus minimus, and iliopsoas tendinopathy was graded normal, tendinosis, low-grade partial tear, high-grade partial tear, or full thickness tear. Gluteus medius, gluteus minimus, tensor fascia lata, and iliopsoas muscle atrophy was scored using a standard scale. Insertion site of tendinopathy and location of muscle atrophy were assessed. Descriptive and statistical analysis was performed. There was increasing greater trochanteric bursitis and gluteus medius and minimus tendinopathy and atrophy with advancing age with moderate to strong positive associations (p < 0.0001) for age and tendinopathy, age and atrophy, bursitis and tendinopathy, and tendinopathy and atrophy for the gluteus medius and minimus. There is a weak positive association (p < 0.0001) for age and tensor fascia lata atrophy, and no statistically significant association between age and tendinopathy or between age and atrophy for the iliopsoas. Fisher's exact tests were statistically significant (p < 0.0001) for insertion site of tendon pathology and location of muscle atrophy for the gluteus medius. Gluteus medius and minimus tendon pathology and muscle atrophy increase with advancing age with progression of tendinosis to low-grade tendon tears to high-grade tendon tears. There is an associated progression in atrophy of these muscles, which may be important in fall-related hip fractures. (orig.)

  10. Computed tomography of skeletal muscles in childhood spinal progressive muscular atrophies

    International Nuclear Information System (INIS)

    Arai, Yumi; Osawa, Makiko; Sumida, Sawako; Shishikura, Keiko; Suzuki, Haruko; Fukuyama, Yukio; Kohno, Atsushi

    1992-01-01

    Computed tomographic (CT) scanning of skeletal muscles was performed in patients with type 1 and type 2 spinal progressive muscular atrophy (SPMA) and Kugelberg-Welander disease (K-W) to delineate the characteristic CT features of each category. Marked muscular atrophy was observed in type 1 SPMA, and both muscular atrophy and intramuscular low density areas in type 2 SPMA, changes being more pronounced in older patients. In contrast, in K-W, muscular atrophy was slight, and intramuscular low density areas constituted the most prominent findings. These observations indicate that SPMA and K-W are each characterized by distinct CT findings. (author)

  11. Lipomatous muscle atrophy caused by irradiation exposure

    International Nuclear Information System (INIS)

    Rhomberg, W.; Hergan, K.

    1990-01-01

    As compared to other organs and tissues liable to sustain delayed injury from radiotherapy, the musculature seems to be a hard-wearing, radiation-resistant organ. Apart from the possibility of inducing Myodegeneratio cordis, muscles are merely threatened, as far as is known today, by possible fibrosis in the surrounding area. Certainly, extremely high doses of more than 100 Gy occasionally may trigger necrosis and atrophies in tissues. The article reports on a patient suffering from carcinoma of the bladder who developed muscle and tendon degeneration following telecobalt irradiation after a latency period of eight years, forcing him ultimately to quit work. (orig.) [de

  12. Muscle atrophy and metal-on-metal hip implants: a serial MRI study of 74 hips.

    Science.gov (United States)

    Berber, Reshid; Khoo, Michael; Cook, Erica; Guppy, Andrew; Hua, Jia; Miles, Jonathan; Carrington, Richard; Skinner, John; Hart, Alister

    2015-06-01

    Muscle atrophy is seen in patients with metal-on-metal (MOM) hip implants, probably because of inflammatory destruction of the musculo-tendon junction. However, like pseudotumors, it is unclear when atrophy occurs and whether it progresses with time. Our objective was to determine whether muscle atrophy associated with MOM hip implants progresses with time. We retrospectively reviewed 74 hips in 56 patients (32 of them women) using serial MRI. Median age was 59 (23-83) years. The median time post-implantation was 83 (35-142) months, and the median interval between scans was 11 months. Hip muscles were scored using the Pfirrmann system. The mean scores for muscle atrophy were compared between the first and second MRI scans. Blood cobalt and chromium concentrations were determined. The median blood cobalt was 6.84 (0.24-90) ppb and median chromium level was 4.42 (0.20-45) ppb. The median Oxford hip score was 34 (5-48). The change in the gluteus minimus mean atrophy score between first and second MRI was 0.12 (p = 0.002). Mean change in the gluteus medius posterior portion (unaffected by surgical approach) was 0.08 (p = 0.01) and mean change in the inferior portion was 0.10 (p = 0.05). Mean pseudotumor grade increased by 0.18 (p = 0.02). Worsening muscle atrophy and worsening pseudotumor grade occur over a 1-year period in a substantial proportion of patients with MOM hip implants. Serial MRI helps to identify those patients who are at risk of developing worsening soft-tissue pathology. These patients should be considered for revision surgery before irreversible muscle destruction occurs.

  13. CT findings of leg muscles in the hemiplegics due to cerebrovascular accidents. Correlation to disuse atrophy

    Energy Technology Data Exchange (ETDEWEB)

    Odajima, Natsu; Ishiai, Sumio; Okiyama, Ryouichi; Furukawa, Tetsuo; Tsukagoshi, Hiroshi

    1987-09-01

    Muscle wastings in hemiplegics due to cerebrovascular accidents were studied with CT scanning in the mid-portion of the thigh and largest-diameter section of the calf bilaterally. Muscle size and average CT density of muscle were measured. The 80 patients were classified into one of the following three stages of disability, i.e. stage 1, severely disabled (wheel-chair-bound but capable of self care (20 patients)); stage 2, moderately disabled (poorly ambulatory (41 patients)); and stage 3, mildly disabled (well ambulatory (19 patients)). Muscle cross-sectional area and CT density in both legs of non-ambulatory patients were smaller and lower than those of other groups. The atrophic change was marked in the affected side, but it was also noticeable in the non-affected side. Gracilis muscle was relatively well spared in all 3 stages. These CT findings of hemiplegics were similar to those of disuse atropy in patients with knee or hip joint lesions. Atrophy was seen first in the quadriceps in thigh and flexor muscle group in calf. These findings were similar to the systemic myogenic or neurogenic atrophies. Although gracilis and sartorius muscles were spared in these systemic deseases, only gracilis muscle was spared in hemiplegics and in patients with disuse atrophy. The ratios of the size of quadriceps, adductor group and sartorius muscle of thigh in affected side to that of non-affected side were smaller in more severely disabled group. Those of the other muscles showed no differences among each stages. In stage 3, there was significant negative correlation between the ratio of quadriceps muscle and periods from the attack. There was no relationship between the severity of the muscle atrophy and parietal lobe lesion. The atrophy is considered to be the result of disuse from immobilization.

  14. Inhibitors of the proteasome reduce the accelerated proteolysis in atrophying rat skeletal muscles.

    Science.gov (United States)

    Tawa, N E; Odessey, R; Goldberg, A L

    1997-07-01

    Several observations have suggested that the enhanced proteolysis and atrophy of skeletal muscle in various pathological states is due primarily to activation of the ubiquitin-proteasome pathway. To test this idea, we investigated whether peptide aldehyde inhibitors of the proteasome, N-acetyl-leucyl-leucyl-norleucinal (LLN), or the more potent CBZ-leucyl-leucyl-leucinal (MG132) suppressed proteolysis in incubated rat skeletal muscles. These agents (e.g., MG132 at 10 microM) inhibited nonlysosomal protein breakdown by up to 50% (P protein synthesis or amino acid pools, but improved overall protein balance in the muscle. Upon treatment with MG132, ubiquitin-conjugated proteins accumulated in the muscle. The inhibition of muscle proteolysis correlated with efficacy against the proteasome, although these agents could also inhibit calpain-dependent proteolysis induced with Ca2+. These inhibitors had much larger effects on proteolysis in atrophying muscles than in controls. In the denervated soleus undergoing atrophy, the increase in ATP-dependent proteolysis was reduced 70% by MG132 (P muscle proteolysis induced by administering thyroid hormones was reduced 40-70% by the inhibitors. Finally, in rats made septic by cecal puncture, the increase in muscle proteolysis was completely blocked by MG132. Thus, the enhanced proteolysis in many catabolic states (including denervation, hyperthyroidism, and sepsis) is due to a proteasome-dependent pathway, and inhibition of proteasome function may be a useful approach to reduce muscle wasting.

  15. Preventive effect of dietary quercetin on disuse muscle atrophy by targeting mitochondria in denervated mice.

    Science.gov (United States)

    Mukai, Rie; Matsui, Naoko; Fujikura, Yutaka; Matsumoto, Norifumi; Hou, De-Xing; Kanzaki, Noriyuki; Shibata, Hiroshi; Horikawa, Manabu; Iwasa, Keiko; Hirasaka, Katsuya; Nikawa, Takeshi; Terao, Junji

    2016-05-01

    Quercetin is a major dietary flavonoid in fruits and vegetables. We aimed to clarify the preventive effect of dietary quercetin on disuse muscle atrophy and the underlying mechanisms. We established a mouse denervation model by cutting the sciatic nerve in the right leg (SNX surgery) to lack of mobilization in hind-limb. Preintake of a quercetin-mixed diet for 14days before SNX surgery prevented loss of muscle mass and atrophy of muscle fibers in the gastrocnemius muscle (GM). Phosphorylation of Akt, a key phosphorylation pathway of suppression of protein degradation, was activated in the quercetin-mixed diet group with and without SNX surgery. Intake of a quercetin-mixed diet suppressed the generation of hydrogen peroxide originating from mitochondria and elevated mitochondrial peroxisome proliferator-activated receptor-γ coactivator 1α mRNA expression as well as NADH dehydrogenase 4 expression in the GM with SNX surgery. Quercetin and its conjugated metabolites reduced hydrogen peroxide production in the mitochondrial fraction obtained from atrophied muscle. In C2C12 myotubes, quercetin reached the mitochondrial fraction. These findings suggest that dietary quercetin can prevent disuse muscle atrophy by targeting mitochondria in skeletal muscle tissue through protecting mitochondria from decreased biogenesis and reducing mitochondrial hydrogen peroxide release, which can be related to decreased hydrogen peroxide production and/or improvements on antioxidant capacity of mitochondria. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Atrophy of sacrospinal muscle groups in patients with chronic, diffusely radiating lumbar back pain

    Energy Technology Data Exchange (ETDEWEB)

    Laasonen, E.M.

    1984-01-01

    After surgery necessitated by lumbar back pain syndromes, radiolucency verified by CT may appear in the sacrospinal muscle group on the operate side. This radiolucency represents muscular atrophy and is in its most severe form a result of the replacement of muscle tissue with adipose tissue. Such muscular atrophy appeared in the present series in 31 out of all 156 patients (19.9%) and in 29 out of 94 patients operated on because of radiating lumbar back pain (30.9%). The radiological appearance, extent, and HU values of this muscular atrophy are presented in detail. Only weak correlations with the multitude of clinical symptoms and signs were found in this retrospective study. The effects of irreversible muscular atrophy on the indications for surgery and physiotherapy are discussed.

  17. Pharmacological inhibition of myostatin suppresses systemic inflammation and muscle atrophy in mice with chronic kidney disease

    Science.gov (United States)

    Zhang, Liping; Rajan, Vik; Lin, Eugene; Hu, Zhaoyong; Han, H. Q.; Zhou, Xiaolan; Song, Yanping; Min, Hosung; Wang, Xiaonan; Du, Jie; Mitch, William E.

    2011-01-01

    Chronic kidney disease (CKD) and several other catabolic conditions are characterized by increased circulating inflammatory cytokines, defects in IGF-1 signaling, abnormal muscle protein metabolism, and progressive muscle atrophy. In these conditions, no reliable treatments successfully block the development of muscle atrophy. In mice with CKD, we found a 2- to 3-fold increase in myostatin expression in muscle. Its pharmacological inhibition by subcutaneous injections of an anti-myostatin peptibody into CKD mice (IC50 ∼1.2 nM) reversed the loss of body weight (≈5–7% increase in body mass) and muscle mass (∼10% increase in muscle mass) and suppressed circulating inflammatory cytokines vs. results from CKD mice injected with PBS. Pharmacological myostatin inhibition also decreased the rate of protein degradation (16.38±1.29%; Pmyostatin expression via a NF-κB-dependent pathway, whereas muscle cells exposed to myostatin stimulated IL-6 production via p38 MAPK and MEK1 pathways. Because IL-6 stimulates muscle protein breakdown, we conclude that CKD increases myostatin through cytokine-activated pathways, leading to muscle atrophy. Myostatin antagonism might become a therapeutic strategy for improving muscle growth in CKD and other conditions with similar characteristics.—Zhang, L., Rajan, V., Lin, E., Hu, Z., Han, H.Q., Zhou, X., Song, Y., Min, H., Wang, X., Du, J., Mitch, W. E. Pharmacological inhibition of myostatin suppresses systemic inflammation and muscle atrophy in mice with chronic kidney disease. PMID:21282204

  18. Implication of altered ubiquitin-proteasome system and ER stress in the muscle atrophy of diabetic rats.

    Science.gov (United States)

    Reddy, S Sreenivasa; Shruthi, Karnam; Prabhakar, Y Konda; Sailaja, Gummadi; Reddy, G Bhanuprakash

    2018-02-01

    Skeletal muscle is adversely affected in type-1 diabetes, and excessively stimulated ubiquitin-proteasome system (UPS) was found to be a leading cause of muscle wasting or atrophy. The role of endoplasmic reticulum (ER) stress in muscle atrophy of type-1 diabetes is not known. Hence, we investigated the role of UPS and ER stress in the muscle atrophy of chronic diabetes rat model. Diabetes was induced with streptozotocin (STZ) in male Sprague-Dawley rats and were sacrificed 2- and 4-months thereafter to collect gastrocnemius muscle. In another experiment, 2-months post-STZ-injection diabetic rats were treated with MG132, a proteasome inhibitor, for the next 2-months and gastrocnemius muscle was collected. The muscle fiber cross-sectional area was diminished in diabetic rats. The expression of UPS components: E1, MURF1, TRIM72, UCHL1, UCHL5, ubiquitinated proteins, and proteasome activity were elevated in the diabetic rats indicating activated UPS. Altered expression of ER-associated degradation (ERAD) components and increased ER stress markers were detected in 4-months diabetic rats. Proteasome inhibition by MG132 alleviated alterations in the UPS and ER stress in diabetic rat muscle. Increased UPS activity and ER stress were implicated in the muscle atrophy of diabetic rats and proteasome inhibition exhibited beneficiary outcome. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Balanced Diet-Fed Fat-1 Transgenic Mice Exhibit Lower Hindlimb Suspension-Induced Soleus Muscle Atrophy.

    Science.gov (United States)

    Marzuca-Nassr, Gabriel Nasri; Murata, Gilson Masahiro; Martins, Amanda Roque; Vitzel, Kaio Fernando; Crisma, Amanda Rabello; Torres, Rosângela Pavan; Mancini-Filho, Jorge; Kang, Jing Xuan; Curi, Rui

    2017-10-06

    The consequences of two-week hindlimb suspension (HS) on skeletal muscle atrophy were investigated in balanced diet-fed Fat-1 transgenic and C57BL/6 wild-type mice. Body composition and gastrocnemius fatty acid composition were measured. Skeletal muscle force, cross-sectional area (CSA), and signaling pathways associated with protein synthesis (protein kinase B, Akt; ribosomal protein S6, S6, eukaryotic translation initiation factor 4E-binding protein 1, 4EBP1; glycogen synthase kinase3-beta, GSK3-beta; and extracellular-signal-regulated kinases 1/2, ERK 1/2) and protein degradation (atrophy gene-1/muscle atrophy F-box, atrogin-1/MAFbx and muscle RING finger 1, MuRF1) were evaluated in the soleus muscle. HS decreased soleus muscle wet and dry weights (by 43% and 26%, respectively), muscle isotonic and tetanic force (by 29% and 18%, respectively), CSA of the soleus muscle (by 36%), and soleus muscle fibers (by 45%). Fat-1 transgenic mice had a decrease in the ω-6/ω-3 polyunsaturated fatty acids (PUFAs) ratio as compared with C57BL/6 wild-type mice (56%, p Balanced diet-fed Fat-1 mice are able to preserve in part the soleus muscle mass, absolute isotonic force and CSA of the soleus muscle in a disuse condition.

  20. Inhibition of FoxO transcriptional activity prevents muscle fiber atrophy during cachexia and induces hypertrophy

    Science.gov (United States)

    Reed, Sarah A.; Sandesara, Pooja B.; Senf, Sarah M.; Judge, Andrew R.

    2012-01-01

    Cachexia is characterized by inexorable muscle wasting that significantly affects patient prognosis and increases mortality. Therefore, understanding the molecular basis of this muscle wasting is of significant importance. Recent work showed that components of the forkhead box O (FoxO) pathway are increased in skeletal muscle during cachexia. In the current study, we tested the physiological significance of FoxO activation in the progression of muscle atrophy associated with cachexia. FoxO-DNA binding dependent transcription was blocked in the muscles of mice through injection of a dominant negative (DN) FoxO expression plasmid prior to inoculation with Lewis lung carcinoma cells or the induction of sepsis. Expression of DN FoxO inhibited the increased mRNA levels of atrogin-1, MuRF1, cathepsin L, and/or Bnip3 and inhibited muscle fiber atrophy during cancer cachexia and sepsis. Interestingly, during control conditions, expression of DN FoxO decreased myostatin expression, increased MyoD expression and satellite cell proliferation, and induced fiber hypertrophy, which required de novo protein synthesis. Collectively, these data show that FoxO-DNA binding-dependent transcription is necessary for normal muscle fiber atrophy during cancer cachexia and sepsis, and further suggest that basal levels of FoxO play an important role during normal conditions to depress satellite cell activation and limit muscle growth.—Reed, S. A., Sandesara, P. B., Senf, S. F., Judge, A. R. Inhibition of FoxO transcriptional activity prevents muscle fiber atrophy during cachexia and induces hypertrophy. PMID:22102632

  1. Overexpression of IGF-I in skeletal muscle of transgenic mice does not prevent unloading-induced atrophy

    Science.gov (United States)

    Criswell, D. S.; Booth, F. W.; DeMayo, F.; Schwartz, R. J.; Gordon, S. E.; Fiorotto, M. L.

    1998-01-01

    This study examined the association between local insulin-like growth factor I (IGF-I) overexpression and atrophy in skeletal muscle. We hypothesized that endogenous skeletal muscle IGF-I mRNA expression would decrease with hindlimb unloading (HU) in mice, and that transgenic mice overexpressing human IGF-I (hIGF-I) specifically in skeletal muscle would exhibit less atrophy after HU. Male transgenic mice and nontransgenic mice from the parent strain (FVB) were divided into four groups (n = 10/group): 1) transgenic, weight-bearing (IGF-I/WB); 2) transgenic, hindlimb unloaded (IGF-I/HU); 3) nontransgenic, weight-bearing (FVB/WB); and 4) nontransgenic, hindlimb unloaded (FVB/HU). HU groups were hindlimb unloaded for 14 days. Body mass was reduced (P < 0.05) after HU in both IGF-I (-9%) and FVB mice (-13%). Contrary to our hypothesis, we found that the relative abundance of mRNA for the endogenous rodent IGF-I (rIGF-I) was unaltered by HU in the gastrocnemius (GAST) muscle of wild-type FVB mice. High-level expression of hIGF-I peptide and mRNA was confirmed in the GAST and tibialis anterior (TA) muscles of the transgenic mice. Nevertheless, masses of the GAST and TA muscles were reduced (P < 0.05) in both FVB/HU and IGF-I/HU groups compared with FVB/WB and IGF-I/WB groups, respectively, and the percent atrophy in mass of these muscles did not differ between FVB and IGF-I mice. Therefore, skeletal muscle atrophy may not be associated with a reduction of endogenous rIGF-I mRNA level in 14-day HU mice. We conclude that high local expression of hIGF-I mRNA and peptide in skeletal muscle alone cannot attenuate unloading-induced atrophy of fast-twitch muscle in mice.

  2. Visual MRI grading system to evaluate atrophy of the supeaspinatus muscle

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Hyun Kyoung; Hong, Sung Hwan; Yoo, Hye Jin; Choi, Ja Young; Kim, Sae Hoon; Choi, Jung Ah; Kang, Heung Sik [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2014-08-15

    To investigate the interobserver reproducibility and diagnostic feasibility of a visual grading system for assessing atrophy of the supraspinatus muscle on magnetic resonance imaging (MRI). Three independent radiologists retrospectively evaluated the occupying ratio of the supraspinatus muscle in the supraspinatus fossa on 192 shoulder MRI examinations in 188 patients using a 3-point visual grading system (1, ≥ 60%; 2, 30-59%; 3, < 30%) on oblique sagittal T1-weighted images. The inter-reader agreement and the agreement with the reference standard (3-point grades according to absolute occupying ratio values quantitatively measured by directly contouring the muscles on MRI) were analyzed using weighted kappa. The visual grading was applied by a single reader to a group of 100 consecutive patients who had undergone rotator cuff repair to retrospectively determine the association between the visual grades at preoperative state and postsurgical occurrences of retear. The inter-reader weighted kappa value for the visual grading was 0.74 when averaged across three reader pairs (0.70-0.77 for individual reader pairs). The weighted kappa value between the visual grading and the reference standard ranged from 0.75 to 0.83. There was a significant difference in retear rates of the rotator cuff between the 3 visual grades of supraspinatus muscle atrophy on MRI in univariable analysis (p < 0.001), but not in multivariable analysis (p = 0.026). The 3-point visual grading system may be a feasible method to assess the severity of supraspinatus muscle atrophy on MRI and assist in the clinical management of patients with rotator cuff tear.

  3. Visual MRI grading system to evaluate atrophy of the supeaspinatus muscle

    International Nuclear Information System (INIS)

    Lim, Hyun Kyoung; Hong, Sung Hwan; Yoo, Hye Jin; Choi, Ja Young; Kim, Sae Hoon; Choi, Jung Ah; Kang, Heung Sik

    2014-01-01

    To investigate the interobserver reproducibility and diagnostic feasibility of a visual grading system for assessing atrophy of the supraspinatus muscle on magnetic resonance imaging (MRI). Three independent radiologists retrospectively evaluated the occupying ratio of the supraspinatus muscle in the supraspinatus fossa on 192 shoulder MRI examinations in 188 patients using a 3-point visual grading system (1, ≥ 60%; 2, 30-59%; 3, < 30%) on oblique sagittal T1-weighted images. The inter-reader agreement and the agreement with the reference standard (3-point grades according to absolute occupying ratio values quantitatively measured by directly contouring the muscles on MRI) were analyzed using weighted kappa. The visual grading was applied by a single reader to a group of 100 consecutive patients who had undergone rotator cuff repair to retrospectively determine the association between the visual grades at preoperative state and postsurgical occurrences of retear. The inter-reader weighted kappa value for the visual grading was 0.74 when averaged across three reader pairs (0.70-0.77 for individual reader pairs). The weighted kappa value between the visual grading and the reference standard ranged from 0.75 to 0.83. There was a significant difference in retear rates of the rotator cuff between the 3 visual grades of supraspinatus muscle atrophy on MRI in univariable analysis (p < 0.001), but not in multivariable analysis (p = 0.026). The 3-point visual grading system may be a feasible method to assess the severity of supraspinatus muscle atrophy on MRI and assist in the clinical management of patients with rotator cuff tear.

  4. Atrophy of sacrospinal muscle groups in patients with chronic, diffusely radiating lumbar back pain

    International Nuclear Information System (INIS)

    Laasonen, E.M.

    1984-01-01

    After surgery necessitated by lumbar back pain syndromes, radiolucency verified by CT may appear in the sacrospinal muscle group on the operate side. This radiolucency represents muscular atrophy and is in its most severe form a result of the replacement of muscle tissue with adipose tissue. Such muscular atrophy appeared in the present series in 31 out of all 156 patients (19.9%) and in 29 out of 94 patients operated on because of radiating lumbar back pain (30.9%). The radiological appearance, extent, and HU values of this muscular atrophy are presented in detail. Only weak correlations with the multitude of clinical symptoms and signs were found in this retrospective study. The effects of irreversible muscular atrophy on the indications for surgery and physiotherapy are discussed. (orig.)

  5. Development of a functional food or drug against unloading-mediated muscle atrophy

    Science.gov (United States)

    Nikawa, Takeshi; Nakao, Reiko; Kagawa, Sachiko; Yamada, Chiharu; Abe, Manami; Tamura, Seiko; Kohno, Shohei; Sukeno, Akiko; Hirasaka, Katsuya; Okumura, Yuushi; Ishidoh, Kazumi

    The ubiquitin-proteasome pathway is a primary regulator of muscle protein turnover, providing a mechanism for selective degradation of regulatory and structural proteins. This pathway is constitutively active in muscle fibers and mediates both intracellular signaling events and normal muscle protein turnover. However, conditions of decreased muscle use, so called unloading, remarkably stimulate activity of this pathway, resulting in loss of muscle protein. In fact, we previously reported that expression of several ubiquitin ligase genes, such as MuRF-1, Cbl-b, and Siah-1A, which are rate-limiting enzymes of the ubiquitin-proteasome proteolytic pathway, are significantly up-regulated in rat skeletal muscle during spaceflight. Moreover, we found that Cbl-b-mediated ubiquitination and degradation of IRS-1, an important intermediates of IGF-1 signal transduction, contributes to muscle atrophy during unloading. Therefore, we hypothesized that inhibition of Cbl-b-mediated ubiquitination and degradation of IRS-1 leads to prevention of muscle atrophy during unloading. In this study, we aimed to evaluate oligopeptide as an inhibitor against ubiquitination of IRS-1 by Cbl-b. We synthesized various oligopeptides that may competitively inhibit the binding of Cbl-b to IRS-1 on the basis of their structures and screened inhibitory effects of these synthesized oligopeptides on Cbl-b-mediated ubiquitination of IRS-1 using in vitro ubiquitination systems. We found that two synthetic oligopeptides with specific amino acid sequences effectively inhibited interaction with Cbl-b and IRS-1, resulting in decreased ubiquitination and degradation of IRS-1 (Patent pending). In contrast, we also found inhibitory activity against Cbl-b-mediated ubiquitination of IRS-1 in soy protein-derived oligopeptides, whereas their inhibitory effects were weaker than those of synthetic oligopeptides. Our results suggest that specific oligopeptides may be available as a functional food against the muscle

  6. Progressive Muscle Atrophy and Weakness After Treatment by Mantle Field Radiotherapy in Hodgkin Lymphoma Survivors

    International Nuclear Information System (INIS)

    Leeuwen-Segarceanu, Elena M. van; Dorresteijn, Lucille D.A.; Pillen, Sigrid; Biesma, Douwe H.; Vogels, Oscar J.M.; Alfen, Nens van

    2012-01-01

    Purpose: To describe the damage to the muscles and propose a pathophysiologic mechanism for muscle atrophy and weakness after mantle field radiotherapy in Hodgkin lymphoma (HL) survivors. Methods and Materials: We examined 12 patients treated by mantle field radiotherapy between 1969 and 1998. Besides evaluation of their symptoms, the following tests were performed: dynamometry; ultrasound of the sternocleidomastoid, biceps, and antebrachial flexor muscles; and needle electromyography of the neck, deltoid, and ultrasonographically affected arm muscles. Results: Ten patients (83%) experienced neck complaints, mostly pain and muscle weakness. On clinical examination, neck flexors were more often affected than neck extensors. On ultrasound, the sternocleidomastoid was severely atrophic in 8 patients, but abnormal echo intensity was seen in only 3 patients. Electromyography of the neck muscles showed mostly myogenic changes, whereas the deltoid, biceps, and antebrachial flexor muscles seemed to have mostly neurogenic damage. Conclusions: Many patients previously treated by mantle field radiotherapy develop severe atrophy and weakness of the neck muscles. Neck muscles within the radiation field show mostly myogenic damage, and muscles outside the mantle field show mostly neurogenic damage. The discrepancy between echo intensity and atrophy suggests that muscle damage is most likely caused by an extrinsic factor such as progressive microvascular fibrosis. This is also presumed to cause damage to nerves within the radiated field, resulting in neurogenic damage of the deltoid and arm muscles.

  7. Distinct responses of protein turnover regulatory pathways in hypoxia- and semistarvation-induced muscle atrophy

    NARCIS (Netherlands)

    de Theije, Chiel C.; Langen, Ramon C. J.; Lamers, Wouter H.; Schols, Annemie M. W. J.; Köhler, S. Eleonore

    2013-01-01

    The balance of muscle protein synthesis and degradation determines skeletal muscle mass. We hypothesized that hypoxia-induced muscle atrophy and alterations in the regulation of muscle protein turnover include a hypoxia-specific component, in addition to the observed effects of reduction in food

  8. Effects of age and inactivity due to prolonged bed rest on atrophy of trunk muscles.

    Science.gov (United States)

    Ikezoe, Tome; Mori, Natsuko; Nakamura, Masatoshi; Ichihashi, Noriaki

    2012-01-01

    This study investigated the effects of age and inactivity due to being chronically bedridden on atrophy of trunk muscles. The subjects comprised 33 young women (young group) and 41 elderly women who resided in nursing homes or chronic care institutions. The elderly subjects were divided into two groups: independent elderly group who were able to perform activities of daily living involving walking independently (n = 28) and dependent elderly group who were chronically bedridden (n = 13). The thickness of the following six trunk muscles was measured by B-mode ultrasound: the rectus abdominis, external oblique, internal oblique, transversus abdominis, thoracic erector spinae (longissimus) and lumbar multifidus muscles. All muscles except for the transversus abdominis and lumbar multifidus muscles were significantly thinner in the independent elderly group compared with those in the young group. The thicknesses of all muscles in the dependent elderly group was significantly smaller than that in the young group, whereas there were no differences between the dependent elderly and independent elderly groups in the muscle thicknesses of the rectus abdominis and internal oblique muscles. In conclusion, our results suggest that: (1) age-related atrophy compared with young women was less in the deep antigravity trunk muscles than the superficial muscles in the independent elderly women; (2) atrophy associated with chronic bed rest was more marked in the antigravity muscles, such as the back and transversus abdominis.

  9. What do we really know about the ubiquitin-proteasome pathway in muscle atrophy?

    Science.gov (United States)

    Jagoe, R. T.; Goldberg, A. L.

    2001-01-01

    Studies of many different rodent models of muscle wasting have indicated that accelerated proteolysis via the ubiquitin-proteasome pathway is the principal cause of muscle atrophy induced by fasting, cancer cachexia, metabolic acidosis, denervation, disuse, diabetes, sepsis, burns, hyperthyroidism and excess glucocorticoids. However, our understanding about how muscle proteins are degraded, and how the ubiquitin-proteasome pathway is activated in muscle under these conditions, is still very limited. The identities of the important ubiquitin-protein ligases in skeletal muscle, and the ways in which they recognize substrates are still largely unknown. Recent in-vitro studies have suggested that one set of ubquitination enzymes, E2(14K) and E3(alpha), which are responsible for the 'N-end rule' system of ubiquitination, plays an important role in muscle, especially in catabolic states. However, their functional significance in degrading different muscle proteins is still unclear. This review focuses on the many gaps in our understanding of the functioning of the ubiquitin-proteasome pathway in muscle atrophy, and highlights the strengths and limitations of the different experimental approaches used in such studies.

  10. Agonist muscle adaptation accompanied by antagonist muscle atrophy in the hindlimb of mice following stretch-shortening contraction training.

    Science.gov (United States)

    Rader, Erik P; Naimo, Marshall A; Ensey, James; Baker, Brent A

    2017-02-02

    The vast majority of dynamometer-based animal models for investigation of the response to chronic muscle contraction exposure has been limited to analysis of isometric, lengthening, or shortening contractions in isolation. An exception to this has been the utilization of a rat model to study stretch-shortening contractions (SSCs), a sequence of consecutive isometric, lengthening, and shortening contractions common during daily activity and resistance-type exercise. However, the availability of diverse genetic strains of rats is limited. Therefore, the purpose of the present study was to develop a dynamometer-based SSC training protocol to induce increased muscle mass and performance in plantarflexor muscles of mice. Young (3 months old) C57BL/6 mice were subjected to 1 month of plantarflexion SSC training. Hindlimb muscles were analyzed for muscle mass, quantitative morphology, myogenesis/myopathy relevant gene expression, and fiber type distribution. The main aim of the research was achieved when training induced a 2-fold increase in plantarflexion peak torque output and a 19% increase in muscle mass for the agonist plantaris (PLT) muscle. In establishing this model, several outcomes emerged which raised the value of the model past that of being a mere recapitulation of the rat model. An increase in the number of muscle fibers per transverse muscle section accounted for the PLT muscle mass gain while the antagonist tibialis anterior (TA) muscle atrophied by 30% with preferential atrophy of type IIb and IIx fibers. These alterations were accompanied by distinct gene expression profiles. The findings confirm the development of a stretch-shortening contraction training model for the PLT muscle of mice and demonstrate that increased cross-sectional fiber number can occur following high-intensity SSC training. Furthermore, the TA muscle atrophy provides direct evidence for the concept of muscle imbalance in phasic non-weight bearing muscles, a concept largely

  11. Pharmacological inhibition of myostatin protects against skeletal muscle atrophy and weakness after anterior cruciate ligament tear.

    Science.gov (United States)

    Wurtzel, Caroline Nw; Gumucio, Jonathan P; Grekin, Jeremy A; Khouri, Roger K; Russell, Alan J; Bedi, Asheesh; Mendias, Christopher L

    2017-11-01

    Anterior cruciate ligament (ACL) tears are among the most frequent knee injuries in sports medicine, with tear rates in the US up to 250,000 per year. Many patients who suffer from ACL tears have persistent atrophy and weakness even after considerable rehabilitation. Myostatin is a cytokine that directly induces muscle atrophy, and previous studies rodent models and patients have demonstrated an upregulation of myostatin after ACL tear. Using a preclinical rat model, our objective was to determine if the use of a bioneutralizing antibody against myostatin could prevent muscle atrophy and weakness after ACL tear. Rats underwent a surgically induced ACL tear and were treated with either a bioneutralizing antibody against myostatin (10B3, GlaxoSmithKline) or a sham antibody (E1-82.15, GlaxoSmithKline). Muscles were harvested at either 7 or 21 days after induction of a tear to measure changes in contractile function, fiber size, and genes involved in muscle atrophy and hypertrophy. These time points were selected to evaluate early and later changes in muscle structure and function. Compared to the sham antibody group, 7 days after ACL tear, myostatin inhibition reduced the expression of proteolytic genes and induced the expression of hypertrophy genes. These early changes in gene expression lead to a 22% increase in muscle fiber cross-sectional area and a 10% improvement in maximum isometric force production that were observed 21 days after ACL tear. Overall, myostatin inhibition lead to several favorable, although modest, changes in molecular biomarkers of muscle regeneration and reduced muscle atrophy and weakness following ACL tear. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2499-2505, 2017. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  12. Effect of IR Laser on Myoblasts: Prospects of Application for Counteracting Microgravity-Induced Muscle Atrophy

    Science.gov (United States)

    Monici, Monica; Cialdai, Francesca; Romano, Giovanni; Corsetto, Paola Antonia; Rizzo, Angela Maria; Caselli, Anna; Ranaldi, Francesco

    2013-02-01

    Microgravity-induced muscle atrophy is a problem of utmost importance for the impact it may have on the health and performance of astronauts. Therefore, appropriate countermeasures are needed to prevent disuse atrophy and favour muscle recovery. Muscle atrophy is characterized by loss of muscle mass and strength, and a shift in substrate utilization from fat to glucose, that leads to a reduced metabolic efficiency and enhanced fatigability. Laser therapy is already used in physical medicine and rehabilitation to accelerate muscle recovery and in sports medicine to prevent damages produced by metabolic disturbances and inflammatory reactions after heavy exercise. The aim of the research we present was to get insights on possible benefits deriving from the application of an advanced infrared laser system to counteract deficits of muscle energy metabolism and stimulate the recovery of the hypotrophic tissue. The source used was a Multiwave Locked System (MLS) laser, which combines continuous and pulsed emissions at 808 nm and 905 nm, respectively. We studied the effect of MLS treatment on morphology and energy metabolism of C2C12 cells, a widely accepted myoblast model, previously exposed to microgravity conditions modelled by a Random Positioning Machine. The MLS laser treatment was able to restore basal levels of serine/threonine protein phosphatase activity and to counteract cytoskeletal alterations and increase in glycolytic enzymes activity that occurred following the exposure to modelled microgravity. In conclusion, the results provide interesting insights for the application of infrared laser in the treatment of muscle atrophy.

  13. Skeletal muscle wasting with disuse atrophy is multi-dimensional: the response and interaction of myonuclei, satellite cells and signaling pathways

    Directory of Open Access Journals (Sweden)

    Naomi Elisabeth Brooks

    2014-03-01

    Full Text Available Maintenance of skeletal muscle is essential for health and survival. There are marked losses of skeletal muscle mass as well as strength and physiological function under conditions of low mechanical load, such as space flight, as well as ground based models such as bed rest, immobilisation, disuse and various animal models. Disuse atrophy is caused by mechanical unloading of muscle and this leads to reduced muscle mass without fibre attrition. Skeletal muscle stem cells (satellite cells and myonuclei are integrally involved in skeletal muscle responses to environmental changes that induce atrophy. Myonuclear domain size is influenced differently in fast and slow twitch muscle, but also by different models of muscle wasting, a factor that is not yet understood. Although the myonuclear domain is 3-dimensional this is rarely considered. Apoptosis as a mechanism for myonuclear loss with atrophy is controversial, whereas cell death of satellite cells has not been considered. Molecular signals such as myostatin/SMAD pathway, MAFbx and MuRF1 E3 ligases of the ubiquitin proteasome pathway and IGF1-AKT-mTOR pathway are 3 distinctly different contributors to skeletal muscle protein adaptation to disuse. Molecular signalling pathways activated in muscle fibres by disuse are rarely considered within satellite cells themselves despite similar exposure to unloading or low mechanical load. These molecular pathways interact with each other during atrophy and also when various interventions are applied that could alleviate atrophy. Re-applying mechanical load is an obvious method to restore muscle mass, however how nutrient supplementation (e.g. amino acids may further enhance recovery (or reduce atrophy despite unloading or ageing is currently of great interest. Satellite cells are particularly responsive to myostatin and to growth factors. Recently, the hibernating squirrel has been identified as an innovative model to study resistance to atrophy.

  14. Inhibition of xanthine oxidase by allopurinol prevents skeletal muscle atrophy: role of p38 MAPKinase and E3 ubiquitin ligases.

    Directory of Open Access Journals (Sweden)

    Frederic Derbre

    Full Text Available Alterations in muscle play an important role in common diseases and conditions. Reactive oxygen species (ROS are generated during hindlimb unloading due, at least in part, to the activation of xanthine oxidase (XO. The major aim of this study was to determine the mechanism by which XO activation causes unloading-induced muscle atrophy in rats, and its possible prevention by allopurinol, a well-known inhibitor of this enzyme. For this purpose we studied one of the main redox sensitive signalling cascades involved in skeletal muscle atrophy i.e. p38 MAPKinase, and the expression of two well known muscle specific E3 ubiquitin ligases involved in proteolysis, the Muscle atrophy F-Box (MAFbx; also known as atrogin-1 and Muscle RING (Really Interesting New Gene Finger-1 (MuRF-1. We found that hindlimb unloading induced a significant increase in XO activity and in the protein expression of the antioxidant enzymes CuZnSOD and Catalase in skeletal muscle. The most relevant new fact reported in this paper is that inhibition of XO with allopurinol, a drug widely used in clinical practice, prevents soleus muscle atrophy by ~20% after hindlimb unloading. This was associated with the inhibition of the p38 MAPK-MAFbx pathway. Our data suggest that XO was involved in the loss of muscle mass via the activation of the p38MAPK-MAFbx pathway in unloaded muscle atrophy. Thus, allopurinol may have clinical benefits to combat skeletal muscle atrophy in bedridden, astronauts, sarcopenic, and cachexic patients.

  15. Clinical Report of Oriental Medicine Treatment with Bee Venom Therapy of Progressive muscle atrophy 1 Patient

    Directory of Open Access Journals (Sweden)

    Kim Young-Ho

    2000-07-01

    Full Text Available The authors reports in order to study the effect of Bee Venom therapy of progressive muscle atrophy. The authors investigated 1 patient who is treated at Woosuk University Oriental Medical Hospital. The patient diagnosed by MRI EMG Hematology Muscle biopsy as progressive muscle atrophy is administered by Bee Venom therapy for 4 months. Bee Venom therapy is operated by 2 times per a week(every 3 days, 0.1cc per one operation, 0.05cc per one acupuncture point. The authors checked changes of this patient's chief symptoms by comparing before and after Bee Venom therapy is operated at 30 times. After Bee Venom therapy, the patient increased motor power & ROM, decreased general cooling sense & swallowing disorder. As above, the authors conclude that better results can be obtained Oriental Medical Treatment with Bee Venom therapy in progressive muscle atrophy

  16. Polar bears experience skeletal muscle atrophy in response to food deprivation and reduced activity in winter and summer

    Science.gov (United States)

    Whiteman, John P.; Harlow, Henry J.; Durner, George M.; Regehr, Eric V.; Rourke, Bryan C.; Robles, Manuel; Amstrup, Steven C.; Ben-David, Merav

    2017-01-01

    When reducing activity and using stored energy during seasonal food shortages, animals risk degradation of skeletal muscles, although some species avoid or minimize the resulting atrophy while experiencing these conditions during hibernation. Polar bears may be food deprived and relatively inactive during winter (when pregnant females hibernate and hunting success declines for other demographic groups) as well as summer (when sea ice retreats from key foraging habitats). We investigated muscle atrophy in samples of biceps femoris collected from free-ranging polar bears in the Southern Beaufort Sea (SBS) throughout their annual cycle. Atrophy was most pronounced in April–May as a result of food deprivation during the previous winter, with muscles exhibiting reduced protein concentration, increased water content, and lower creatine kinase mRNA. These animals increased feeding and activity in spring (when seal prey becomes more available), initiating a period of muscle recovery. During the following ice melt of late summer, ~30% of SBS bears abandon retreating sea ice for land; in August, these ‘shore’ bears exhibited no muscle atrophy, indicating that they had fully recovered from winter food deprivation. These individuals subsequently scavenged whale carcasses deposited by humans and by October, had retained good muscle condition. In contrast, ~70% of SBS bears follow the ice north in late summer, into deep water with less prey. These ‘ice’ bears fast; by October, they exhibited muscle protein loss and rapid changes in myosin heavy-chain isoforms in response to reduced activity. These findings indicate that, unlike other bears during winter hibernation, polar bears without food in summer cannot mitigate atrophy. Consequently, prolonged summer fasting resulting from climate change-induced ice loss creates a risk of greater muscle atrophy and reduced abilities to travel and hunt.

  17. Polar bears experience skeletal muscle atrophy in response to food deprivation and reduced activity in winter and summer

    Science.gov (United States)

    Harlow, Henry J.; Durner, George M.; Regehr, Eric V.; Rourke, Bryan C.; Robles, Manuel; Amstrup, Steven C.; Ben-David, Merav

    2017-01-01

    Abstract When reducing activity and using stored energy during seasonal food shortages, animals risk degradation of skeletal muscles, although some species avoid or minimize the resulting atrophy while experiencing these conditions during hibernation. Polar bears may be food deprived and relatively inactive during winter (when pregnant females hibernate and hunting success declines for other demographic groups) as well as summer (when sea ice retreats from key foraging habitats). We investigated muscle atrophy in samples of biceps femoris collected from free-ranging polar bears in the Southern Beaufort Sea (SBS) throughout their annual cycle. Atrophy was most pronounced in April–May as a result of food deprivation during the previous winter, with muscles exhibiting reduced protein concentration, increased water content, and lower creatine kinase mRNA. These animals increased feeding and activity in spring (when seal prey becomes more available), initiating a period of muscle recovery. During the following ice melt of late summer, ~30% of SBS bears abandon retreating sea ice for land; in August, these ‘shore’ bears exhibited no muscle atrophy, indicating that they had fully recovered from winter food deprivation. These individuals subsequently scavenged whale carcasses deposited by humans and by October, had retained good muscle condition. In contrast, ~70% of SBS bears follow the ice north in late summer, into deep water with less prey. These ‘ice’ bears fast; by October, they exhibited muscle protein loss and rapid changes in myosin heavy-chain isoforms in response to reduced activity. These findings indicate that, unlike other bears during winter hibernation, polar bears without food in summer cannot mitigate atrophy. Consequently, prolonged summer fasting resulting from climate change-induced ice loss creates a risk of greater muscle atrophy and reduced abilities to travel and hunt. PMID:28835844

  18. Polar bears experience skeletal muscle atrophy in response to food deprivation and reduced activity in winter and summer.

    Science.gov (United States)

    Whiteman, John P; Harlow, Henry J; Durner, George M; Regehr, Eric V; Rourke, Bryan C; Robles, Manuel; Amstrup, Steven C; Ben-David, Merav

    2017-01-01

    When reducing activity and using stored energy during seasonal food shortages, animals risk degradation of skeletal muscles, although some species avoid or minimize the resulting atrophy while experiencing these conditions during hibernation. Polar bears may be food deprived and relatively inactive during winter (when pregnant females hibernate and hunting success declines for other demographic groups) as well as summer (when sea ice retreats from key foraging habitats). We investigated muscle atrophy in samples of biceps femoris collected from free-ranging polar bears in the Southern Beaufort Sea (SBS) throughout their annual cycle. Atrophy was most pronounced in April-May as a result of food deprivation during the previous winter, with muscles exhibiting reduced protein concentration, increased water content, and lower creatine kinase mRNA. These animals increased feeding and activity in spring (when seal prey becomes more available), initiating a period of muscle recovery. During the following ice melt of late summer, ~30% of SBS bears abandon retreating sea ice for land; in August, these 'shore' bears exhibited no muscle atrophy, indicating that they had fully recovered from winter food deprivation. These individuals subsequently scavenged whale carcasses deposited by humans and by October, had retained good muscle condition. In contrast, ~70% of SBS bears follow the ice north in late summer, into deep water with less prey. These 'ice' bears fast; by October, they exhibited muscle protein loss and rapid changes in myosin heavy-chain isoforms in response to reduced activity. These findings indicate that, unlike other bears during winter hibernation, polar bears without food in summer cannot mitigate atrophy. Consequently, prolonged summer fasting resulting from climate change-induced ice loss creates a risk of greater muscle atrophy and reduced abilities to travel and hunt.

  19. miRNA targeted signaling pathway in the early stage of denervated fast and slow muscle atrophy

    Directory of Open Access Journals (Sweden)

    Gang Li

    2016-01-01

    Full Text Available Denervation often results in skeletal muscle atrophy. Different mechanisms seem to be involved in the determination between denervated slow and fast skeletal muscle atrophy. At the epigenetic level, miRNAs are thought to be highly involved in the pathophysiological progress of denervated muscles. We used miRNA microarrays to determine miRNA expression profiles from a typical slow muscle (soleus muscle and a typical fast muscle (tibialis anterior muscle at an early denervation stage in a rat model. Results showed that miR-206, miR-195, miR-23a, and miR-30e might be key factors in the transformation process from slow to fast muscle in denervated slow muscles. Additionally, certain miRNA molecules (miR-214, miR-221, miR-222, miR-152, miR-320, and Let-7e could be key regulatory factors in the denervated atrophy process involved in fast muscle. Analysis of signaling pathway networks revealed the miRNA molecules that were responsible for regulating certain signaling pathways, which were the final targets (e.g., p38 MAPK pathway; Pax3/Pax7 regulates Utrophin and follistatin by HDAC4; IGF1/PI3K/Akt/mTOR pathway regulates atrogin-1 and MuRF1 expression via FoxO phosphorylation. Our results provide a better understanding of the mechanisms of denervated skeletal muscle pathophysiology.

  20. Acylated and unacylated ghrelin impair skeletal muscle atrophy in mice

    Science.gov (United States)

    Cachexia is a wasting syndrome associated with cancer, AIDS, multiple sclerosis, and several other disease states. It is characterized by weight loss, fatigue, loss of appetite, and skeletal muscle atrophy and is associated with poor patient prognosis, making it an important treatment target. Ghreli...

  1. Aging augments the impact of influenza respiratory tract infection on mobility impairments, muscle-localized inflammation, and muscle atrophy.

    Science.gov (United States)

    Bartley, Jenna M; Pan, Sarah J; Keilich, Spencer R; Hopkins, Jacob W; Al-Naggar, Iman M; Kuchel, George A; Haynes, Laura

    2016-04-01

    Although the influenza virus only infects the respiratory system, myalgias are commonly experienced during infection. In addition to a greater risk of hospitalization and death, older adults are more likely to develop disability following influenza infection; however, this relationship is understudied. We hypothesized that upon challenge with influenza, aging would be associated with functional impairments, as well as upregulation of skeletal muscle inflammatory and atrophy genes. Infected young and aged mice demonstrated decreased mobility and altered gait kinetics. These declines were more prominent in hind limbs and in aged mice. Skeletal muscle expression of genes involved in inflammation, as well as muscle atrophy and proteolysis, increased during influenza infection with an elevated and prolonged peak in aged mice. Infection also decreased expression of positive regulators of muscle mass and myogenesis components to a greater degree in aged mice. Gene expression correlated to influenza-induced body mass loss, although evidence did not support direct muscle infection. Overall, influenza leads to mobility impairments with induction of inflammatory and muscle degradation genes and downregulation of positive regulators of muscle. These effects are augmented and prolonged with aging, providing a molecular link between influenza infection, decreased resilience and increased risk of disability in the elderly.

  2. Eccentric exercise training as a countermeasure to non-weight-bearing soleus muscle atrophy

    Science.gov (United States)

    Kirby, Christopher R.; Ryan, Mirelle J.; Booth, Frank W.

    1992-01-01

    This investigation tested whether eccentric resistance training could prevent soleus muscle atrophy during non-weight bearing. Adult female rats were randomly assigned to either weight bearing +/- intramuscular electrodes or non-weight bearing +/- intramuscular electrodes groups. Electrically stimulated maximal eccentric contractions were performed on anesthetized animals at 48-h intervals during the 10-day experiment. Non-weight bearing significantly reduced soleus muscle wet weight (28-31 percent) and noncollagenous protein content (30-31 percent) compared with controls. Eccentric exercise training during non-weight bearing attenuated but did not prevent the loss of soleus muscle wet weight and noncollagenous protein by 77 and 44 percent, respectively. The potential of eccentric exercise training as an effective and highly efficient counter-measure to non-weight-bearing atrophy is demonstrated in the 44 percent attenuation of soleus muscle noncollagenous protein loss by eccentric exercise during only 0.035 percent of the total non-weight-bearing time period.

  3. MRI of rotator cuff muscle atrophy in relation to glenohumeral joint incongruence in brachial plexus birth injury

    International Nuclear Information System (INIS)

    Poeyhiae, Tiina H.; Nietosvaara, Yrjaenae A.; Peltonen, Jari I.; Remes, Ville M.; Kirjavainen, Mikko O.; Lamminen, Antti E.

    2005-01-01

    Purpose: To evaluate rotator cuff muscles and the glenohumeral (GH) joint in brachial plexus birth injury (BPBI) using MRI and to determine whether any correlation exists between muscular abnormality and the development of glenoid dysplasia and GH joint incongruity. Thirty-nine consecutive BPBI patients with internal rotation contracture or absent active external rotation of the shoulder joint were examined clinically and imaged with MRI. In the physical examination, passive external rotation was measured to evaluate internal rotation contracture. Both shoulders were imaged and the glenoscapular angle, percentage of humeral head anterior to the middle of the glenoid fossa (PHHA) and the greatest thickness of the subscapular, infraspinous and supraspinous muscles were measured. The muscle ratio between the affected side and the normal side was calculated to exclude age variation in the assessment of muscle atrophy. All muscles of the rotator cuff were atrophic, with the subscapular and infraspinous muscles being most severely affected. A correlation was found between the percentage of humeral head anterior to the middle of the glenoid fossa (PHHA) and the extent of subscapular muscle atrophy (r s =0.45, P=0.01), as well as between its ratio (r s =0.5, P P=0.01). Severity of rotator cuff muscle atrophy correlated with increased glenoid retroversion and the degree of internal rotation contracture. Glenoid retroversion and subluxation of the humeral head are common in patients with BPBI. All rotator cuff muscles are atrophic, especially the subscapular muscle. Muscle atrophy due to neurogenic damage apparently results in an imbalance of the shoulder muscles and progressive retroversion and subluxation of the GH joint, which in turn lead to internal rotation contracture and deformation of the joint. (orig.)

  4. Muscle atrophy in patients wirh ckd results from fgf23/klotho-mediated supression of insulin/igf-i signaling

    Directory of Open Access Journals (Sweden)

    Shinsuke Kido

    2012-06-01

    Full Text Available Muscle atrophy is a significant consequence of chronic kidney disease (CKD that increases a patient’s risk of mortality and decrease their quality of life. In CKD patients, the circulation levels of FGF23 are significantly increased, but the exact pathological significance of the increase and relationship between FGF23 and muscle atrophy are not clear. Because of Klohto, acts as a co-receptor of FGF23 is detectable in limited tissues including in kidney and brain, but not in skeletal muscles. In contrast, recently reports indicated that the extracellular domain of klohto is cleavage for some reason on the cell surface and detected in the blood in animals. In this study, we attempted to identify the causative factors responsible for the shedding of Klotho, and whether both FGF23 and Klohto induced muscle atrophy via reduction of insulin/IGF-I signaling. We first investigated by treating kidney cells with various factors related in pathological factors in CKD. As a result, we found that advanced glycation endproducts (AGEs, an accumulated in patients with CKD and diabetes mellitus, increases shedding of Klohto in kidney cells. It is common knowledge that insulin/IGF-I signaling is necessary for normal skeletal growth. As a result, we showed that both FGF23 and Klohto inhibited differentiation of cultured skeletal muscle cells through down-regulation of insulin/IGF-I signaling. These observations suggested a divergent role of FGF23 and soluble klohto in the regulation of skeletal muscle differentiation and thereby muscle atrophy under pathological conditioned in CKD patients. Our results further imply that FGF23/Klohto may serve a new therapeutic target for CKD-induced muscle atrophy.

  5. Balanced Diet-Fed Fat-1 Transgenic Mice Exhibit Lower Hindlimb Suspension-Induced Soleus Muscle Atrophy

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    Gabriel Nasri Marzuca-Nassr

    2017-10-01

    Full Text Available The consequences of two-week hindlimb suspension (HS on skeletal muscle atrophy were investigated in balanced diet-fed Fat-1 transgenic and C57BL/6 wild-type mice. Body composition and gastrocnemius fatty acid composition were measured. Skeletal muscle force, cross-sectional area (CSA, and signaling pathways associated with protein synthesis (protein kinase B, Akt; ribosomal protein S6, S6, eukaryotic translation initiation factor 4E-binding protein 1, 4EBP1; glycogen synthase kinase3-beta, GSK3-beta; and extracellular-signal-regulated kinases 1/2, ERK 1/2 and protein degradation (atrophy gene-1/muscle atrophy F-box, atrogin-1/MAFbx and muscle RING finger 1, MuRF1 were evaluated in the soleus muscle. HS decreased soleus muscle wet and dry weights (by 43% and 26%, respectively, muscle isotonic and tetanic force (by 29% and 18%, respectively, CSA of the soleus muscle (by 36%, and soleus muscle fibers (by 45%. Fat-1 transgenic mice had a decrease in the ω-6/ω-3 polyunsaturated fatty acids (PUFAs ratio as compared with C57BL/6 wild-type mice (56%, p < 0.001. Fat-1 mice had lower soleus muscle dry mass loss (by 10% and preserved absolute isotonic force (by 17% and CSA of the soleus muscle (by 28% after HS as compared with C57BL/6 wild-type mice. p-GSK3B/GSK3B ratio was increased (by 70% and MuRF-1 content decreased (by 50% in the soleus muscle of Fat-1 mice after HS. Balanced diet-fed Fat-1 mice are able to preserve in part the soleus muscle mass, absolute isotonic force and CSA of the soleus muscle in a disuse condition.

  6. Apoptosis-inducing effect of selective sensory or motor nerve injury on skeletal muscle atrophy

    Directory of Open Access Journals (Sweden)

    Lei ZHAO

    2011-09-01

    Full Text Available Objective To explore the apoptosis-inducing effect of selective sensory or motor nerve injury on skeletal muscle atrophy.Methods Thirty healthy adult SD rats were randomly divided into three groups,namely,ventral root transection group(VRT group,received left L4-L6 ventral rhizotomy,dorsal root transection group(DRT group,received left L4-L6 dorsal rhizotomy,and sciatic nerve transection group(SNT group,received left sciatic nerve transection.Each group comprised 10 SD rats.The bilateral gastrocnemius was harvested 10 weeks after operation to observe the apoptosis and Fas/FasL expression of the skeletal muscle cells through fluorescent labeling,transmission electron microscopy,and immunohistochemistry.Result Ten weeks after the denervation,apoptosis-related changes,especially obvious changes of the nuclear apoptotic morphology,were observed in the skeletal muscle cells.The aggregation degree of the nucleus and the expression of Fas/FasL increased in the following order: DRT group,VRT group,and SNT group.No apoptotic body,but early apoptotic morphology,was found in the denervated gastrocnemius through transmission electron microscopy.Conclusions The effect of motor nerve injury on skeletal muscle atrophy is more serious than that of sensory nerve injury.The rebuilding of motor nerves should be preferentially considered in the clinical treatment of muscle atrophy induced by denervation.

  7. Local Overexpression of V1a-Vasopressin Receptor Enhances Regeneration in Tumor Necrosis Factor-Induced Muscle Atrophy

    Directory of Open Access Journals (Sweden)

    Alessandra Costa

    2014-01-01

    Full Text Available Skeletal muscle atrophy occurs during disuse and aging, or as a consequence of chronic diseases such as cancer and diabetes. It is characterized by progressive loss of muscle tissue due to hypotrophic changes, degeneration, and an inability of the regeneration machinery to replace damaged myofibers. Tumor necrosis factor (TNF is a proinflammatory cytokine known to mediate muscle atrophy in many chronic diseases and to inhibit skeletal muscle regeneration. In this study, we investigated the role of Arg-vasopressin-(AVP-dependent pathways in muscles in which atrophy was induced by local overexpression of TNF. AVP is a potent myogenesis-promoting factor and is able to enhance skeletal muscle regeneration by stimulating Ca2+/calmodulin-dependent kinase and calcineurin signaling. We performed morphological and molecular analyses and demonstrated that local over-expression of the AVP receptor V1a enhances regeneration of atrophic muscle. By upregulating the regeneration/differentiation markers, modulating the inflammatory response, and attenuating fibrogenesis, the stimulation of AVP-dependent pathways creates a favourable environment for efficient and sustained muscle regeneration and repair even in the presence of elevated levels of TNF. This study highlights a novel in vivo role for AVP-dependent pathways, which may represent an interesting strategy to counteract muscle decline in aging or in muscular pathologies.

  8. Protection against dexamethasone-induced muscle atrophy is related to modulation by testosterone of FOXO1 and PGC-1{alpha}

    Energy Technology Data Exchange (ETDEWEB)

    Qin, Weiping, E-mail: weiping.qin@mssm.edu [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peters VA Medical Center, Bronx, NY (United States); Department of Medicine, Mount Sinai School of Medicine, NY (United States); Pan, Jiangping; Wu, Yong [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peters VA Medical Center, Bronx, NY (United States); Bauman, William A. [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peters VA Medical Center, Bronx, NY (United States); Department of Medicine, Mount Sinai School of Medicine, NY (United States); Department of Rehabilitation Medicine, Mount Sinai School of Medicine, NY (United States); Cardozo, Christopher, E-mail: Chris.Cardozo@mssm.edu [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peters VA Medical Center, Bronx, NY (United States); Department of Medicine, Mount Sinai School of Medicine, NY (United States); Department of Rehabilitation Medicine, Mount Sinai School of Medicine, NY (United States)

    2010-12-17

    Research highlights: {yields} In rat gastrocnemius muscle, dexamethasone reduced PGC-1{alpha} cellular and nuclear levels without altering mRNA levels for this factor. {yields} Dexamethasone reduced phosphorylating of p38 MAPK, which stabilizes PGC-1{alpha} and promotes its nuclear entry. {yields} Co-administration of testosterone with dexamethasone increased cellular and nuclear levels of PGC-1{alpha} protein without changing its mRNA levels. {yields} Co-administration of testosterone restored p38 MAPK levels to those of controls. -- Abstract: Glucocorticoid-induced muscle atrophy results from muscle protein catabolism and reduced protein synthesis, associated with increased expression of two muscle-specific ubiquitin ligases (MAFbx and MuRF1), and of two inhibitors of protein synthesis, REDD1 and 4EBP1. MAFbx, MuRF1, REDD1 and 4EBP1 are up-regulated by the transcription factors FOXO1 and FOXO3A. The transcriptional co-activator PGC-1{alpha} has been shown to attenuate many forms of muscle atrophy and to repress FOXO3A-mediated transcription of atrophy-specific genes. Dexamethasone-induced muscle atrophy can be prevented by testosterone, which blocks up-regulation by dexamethasone of FOXO1. Here, an animal model of dexamethasone-induced muscle atrophy was used to further characterize effects of testosterone to abrogate adverse actions of dexamethasone on FOXO1 levels and nuclear localization, and to determine how these agents affect PGC-1{alpha}, and its upstream activators, p38 MAPK and AMPK. In rat gastrocnemius muscle, testosterone blunted the dexamethasone-mediated increase in levels of FOXO1 mRNA, and FOXO1 total and nuclear protein. Dexamethasone reduced total and nuclear PGC-1{alpha} protein levels in the gastrocnemius; co-administration of testosterone with dexamethasone increased total and nuclear PGC-1{alpha} levels above those present in untreated controls. Testosterone blocked dexamethasone-induced decreases in activity of p38 MAPK in the gastrocnemius

  9. Pattern Differences of Small Hand Muscle Atrophy in Amyotrophic Lateral Sclerosis and Mimic Disorders.

    Science.gov (United States)

    Fang, Jia; Liu, Ming-Sheng; Guan, Yu-Zhou; Du, Hua; Li, Ben-Hong; Cui, Bo; Ding, Qing-Yun; Cui, Li-Ying

    2016-04-05

    Amyotrophic lateral sclerosis (ALS) and some mimic disorders, such as distal-type cervical spondylotic amyotrophy (CSA), Hirayama disease (HD), and spinobulbar muscular atrophy (SBMA) may present with intrinsic hand muscle atrophy. This study aimed to investigate different patterns of small hand muscle involvement in ALS and some mimic disorders. We compared the abductor digiti minimi/abductor pollicis brevis (ADM/APB) compound muscle action potential (CMAP) ratios between 200 ALS patients, 95 patients with distal-type CSA, 88 HD patients, 43 SBMA patients, and 150 normal controls. The ADM/APB CMAP amplitude ratio was significantly higher in the ALS patients (P mimic disorders presumably reflect distinct pathophysiological mechanisms underlying different disorders, and may aid in distinguishing between ALS and mimic disorders.

  10. Effects of Nandrolone in the Counteraction of Skeletal Muscle Atrophy in a Mouse Model of Muscle Disuse: Molecular Biology and Functional Evaluation.

    Directory of Open Access Journals (Sweden)

    Giulia Maria Camerino

    Full Text Available Muscle disuse produces severe atrophy and a slow-to-fast phenotype transition in the postural Soleus (Sol muscle of rodents. Antioxidants, amino-acids and growth factors were ineffective to ameliorate muscle atrophy. Here we evaluate the effects of nandrolone (ND, an anabolic steroid, on mouse skeletal muscle atrophy induced by hindlimb unloading (HU. Mice were pre-treated for 2-weeks before HU and during the 2-weeks of HU. Muscle weight and total protein content were reduced in HU mice and a restoration of these parameters was found in ND-treated HU mice. The analysis of gene expression by real-time PCR demonstrates an increase of MuRF-1 during HU but minor involvement of other catabolic pathways. However, ND did not affect MuRF-1 expression. The evaluation of anabolic pathways showed no change in mTOR and eIF2-kinase mRNA expression, but the protein expression of the eukaryotic initiation factor eIF2 was reduced during HU and restored by ND. Moreover we found an involvement of regenerative pathways, since the increase of MyoD observed after HU suggests the promotion of myogenic stem cell differentiation in response to atrophy. At the same time, Notch-1 expression was down-regulated. Interestingly, the ND treatment prevented changes in MyoD and Notch-1 expression. On the contrary, there was no evidence for an effect of ND on the change of muscle phenotype induced by HU, since no effect of treatment was observed on the resting gCl, restCa and contractile properties in Sol muscle. Accordingly, PGC1α and myosin heavy chain expression, indexes of the phenotype transition, were not restored in ND-treated HU mice. We hypothesize that ND is unable to directly affect the phenotype transition when the specialized motor unit firing pattern of stimulation is lacking. Nevertheless, through stimulation of protein synthesis, ND preserves protein content and muscle weight, which may result advantageous to the affected skeletal muscle for functional recovery.

  11. An Antibody Blocking Activin Type II Receptors Induces Strong Skeletal Muscle Hypertrophy and Protects from Atrophy

    Science.gov (United States)

    Minetti, Giulia C.; Sheppard, KellyAnn; Ibebunjo, Chikwendu; Feige, Jerome N.; Hartmann, Steffen; Brachat, Sophie; Rivet, Helene; Koelbing, Claudia; Morvan, Frederic; Hatakeyama, Shinji

    2014-01-01

    The myostatin/activin type II receptor (ActRII) pathway has been identified to be critical in regulating skeletal muscle size. Several other ligands, including GDF11 and the activins, signal through this pathway, suggesting that the ActRII receptors are major regulatory nodes in the regulation of muscle mass. We have developed a novel, human anti-ActRII antibody (bimagrumab, or BYM338) to prevent binding of ligands to the receptors and thus inhibit downstream signaling. BYM338 enhances differentiation of primary human skeletal myoblasts and counteracts the inhibition of differentiation induced by myostatin or activin A. BYM338 prevents myostatin- or activin A-induced atrophy through inhibition of Smad2/3 phosphorylation, thus sparing the myosin heavy chain from degradation. BYM338 dramatically increases skeletal muscle mass in mice, beyond sole inhibition of myostatin, detected by comparing the antibody with a myostatin inhibitor. A mouse version of the antibody induces enhanced muscle hypertrophy in myostatin mutant mice, further confirming a beneficial effect on muscle growth beyond myostatin inhibition alone through blockade of ActRII ligands. BYM338 protects muscles from glucocorticoid-induced atrophy and weakness via prevention of muscle and tetanic force losses. These data highlight the compelling therapeutic potential of BYM338 for the treatment of skeletal muscle atrophy and weakness in multiple settings. PMID:24298022

  12. Direct optical activation of skeletal muscle fibres efficiently controls muscle contraction and attenuates denervation atrophy.

    Science.gov (United States)

    Magown, Philippe; Shettar, Basavaraj; Zhang, Ying; Rafuse, Victor F

    2015-10-13

    Neural prostheses can restore meaningful function to paralysed muscles by electrically stimulating innervating motor axons, but fail when muscles are completely denervated, as seen in amyotrophic lateral sclerosis, or after a peripheral nerve or spinal cord injury. Here we show that channelrhodopsin-2 is expressed within the sarcolemma and T-tubules of skeletal muscle fibres in transgenic mice. This expression pattern allows for optical control of muscle contraction with comparable forces to nerve stimulation. Force can be controlled by varying light pulse intensity, duration or frequency. Light-stimulated muscle fibres depolarize proportionally to light intensity and duration. Denervated triceps surae muscles transcutaneously stimulated optically on a daily basis for 10 days show a significant attenuation in atrophy resulting in significantly greater contractile forces compared with chronically denervated muscles. Together, this study shows that channelrhodopsin-2/H134R can be used to restore function to permanently denervated muscles and reduce pathophysiological changes associated with denervation pathologies.

  13. Regulatory circuitry of TWEAK-Fn14 system and PGC-1α in skeletal muscle atrophy program.

    Science.gov (United States)

    Hindi, Sajedah M; Mishra, Vivek; Bhatnagar, Shephali; Tajrishi, Marjan M; Ogura, Yuji; Yan, Zhen; Burkly, Linda C; Zheng, Timothy S; Kumar, Ashok

    2014-03-01

    Skeletal muscle wasting attributed to inactivity has significant adverse functional consequences. Accumulating evidence suggests that peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) and TNF-like weak inducer of apoptosis (TWEAK)-Fn14 system are key regulators of skeletal muscle mass in various catabolic states. While the activation of TWEAK-Fn14 signaling causes muscle wasting, PGC-1α preserves muscle mass in several conditions, including functional denervation and aging. However, it remains unknown whether there is any regulatory interaction between PGC-1α and TWEAK-Fn14 system during muscle atrophy. Here we demonstrate that TWEAK significantly reduces the levels of PGC-1α and mitochondrial content (∼50%) in skeletal muscle. Levels of PGC-1α are significantly increased in skeletal muscle of TWEAK-knockout (KO) and Fn14-KO mice compared to wild-type mice on denervation. Transgenic (Tg) overexpression of PGC-1α inhibited progressive muscle wasting in TWEAK-Tg mice. PGC-1α inhibited the TWEAK-induced activation of NF-κB (∼50%) and dramatically reduced (∼90%) the expression of atrogenes such as MAFbx and MuRF1. Intriguingly, muscle-specific overexpression of PGC-1α also prevented the inducible expression of Fn14 in denervated skeletal muscle. Collectively, our study demonstrates that TWEAK induces muscle atrophy through repressing the levels of PGC-1α. Overexpression of PGC-1α not only blocks the TWEAK-induced atrophy program but also diminishes the expression of Fn14 in denervated skeletal muscle.

  14. Muscle Plasticity and β2-Adrenergic Receptors: Adaptive Responses of β2-Adrenergic Receptor Expression to Muscle Hypertrophy and Atrophy

    OpenAIRE

    Shogo Sato; Ken Shirato; Kaoru Tachiyashiki; Kazuhiko Imaizumi

    2011-01-01

    We discuss the functional roles of β2-adrenergic receptors in skeletal muscle hypertrophy and atrophy as well as the adaptive responses of β2-adrenergic receptor expression to anabolic and catabolic conditions. β2-Adrenergic receptor stimulation using anabolic drugs increases muscle mass by promoting muscle protein synthesis and/or attenuating protein degradation. These effects are prevented ...

  15. Altered myoplasmic Ca(2+) handling in rat fast-twitch skeletal muscle fibres during disuse atrophy.

    Science.gov (United States)

    Weiss, Norbert; Andrianjafiniony, Tina; Dupré-Aucouturier, Sylvie; Pouvreau, Sandrine; Desplanches, Dominique; Jacquemond, Vincent

    2010-03-01

    Calcium-dependent signalling pathways are believed to play an important role in skeletal muscle atrophy, but whether intracellular Ca(2+) homeostasis is affected in that situation remains obscure. We show here that there is a 20% atrophy of the fast-type flexor digitorum brevis (FDB) muscle in rats hind limb unloaded (HU) for 2 weeks, with no change in fibre type distribution. In voltage-clamp experiments, the amplitude of the slow Ca(2+) current was found similar in fibres from control and HU animals. In fibres loaded with the Ca(2+) dye indo-1, the value for the rate of [Ca(2+)] decay after the end of 5-100-ms-long voltage-clamp depolarisations from -80 to +10 mV was found to be 30-50% lower in fibres from HU animals. This effect was consistent with a reduced contribution of both saturable and non-saturable components of myoplasmic Ca(2+) removal. However, there was no change in the relative amount of parvalbumin, and type 1 sarco-endoplasmic reticulum Ca(2+)-ATPase was increased by a factor of three in the atrophied muscles. Confocal imaging of mitochondrial membrane potential showed that atrophied FDB fibres had significantly depolarized mitochondria as compared to control fibres. Depolarization of mitochondria in control fibres with carbonyl cyanide-p-trifluoromethoxyphenylhydrazone induced a slowing of the decay of [Ca(2+)] transients accompanied by an increase in resting [Ca(2+)] and a reduction of the peak amplitude of the transients. Overall results provide the first functional evidence for severely altered intracellular Ca(2+) removal capabilities in atrophied fast-type muscle fibres and highlight the possible contribution of reduced mitochondrial polarisation.

  16. Pyrrolidine Dithiocarbamate (PDTC Attenuates Cancer Cachexia by Affecting Muscle Atrophy and Fat Lipolysis

    Directory of Open Access Journals (Sweden)

    Chunxiao Miao

    2017-12-01

    Full Text Available Cancer cachexia is a kind of whole body metabolic disorder syndrome accompanied with severe wasting of muscle and adipose tissue. NF-κB signaling plays an important role during skeletal muscle atrophy and fat lipolysis. As an inhibitor of NF-κB signaling, Pyrrolidine dithiocarbamate (PDTC was reported to relieve cancer cachexia; however, its mechanism remains largely unknown. In our study, we showed that PDTC attenuated cancer cachexia symptom in C26 tumor bearing mice models in vivo without influencing tumor volume. What’s more, PDTC inhibited muscle atrophy and lipolysis in cells models in vitro induced by TNFα and C26 tumor medium. PDTC suppressed atrophy of myotubes differentiated from C2C12 by reducing MyoD and upregulating MuRF1, and preserving the expression of perilipin as well as blocking the activation of HSL in 3T3-L1 mature adipocytes. Meaningfully, we observed that PDTC also inhibited p38 MAPK signaling besides the NF-κB signaling in cancer cachexia in vitro models. In addition, PDTC also influenced the protein synthesis of skeletal muscle by activating AKT signaling and regulated fat energy metabolism by inhibiting AMPK signaling. Therefore, PDTC primarily influenced different pathways in different tissues. The study not only established a simple and reliable screening drugs model of cancer cachexia in vitro but also provided new theoretical basis for future treatment of cancer cachexia.

  17. Anti-skeletal muscle atrophy effect of Oenothera odorata root extract via reactive oxygen species-dependent signaling pathways in cellular and mouse model.

    Science.gov (United States)

    Lee, Yong-Hyeon; Kim, Wan-Joong; Lee, Myung-Hun; Kim, Sun-Young; Seo, Dong-Hyun; Kim, Han-Sung; Gelinsky, Michael; Kim, Tack-Joong

    2016-01-01

    Skeletal muscle atrophy can be defined as a decrease of muscle volume caused by injury or lack of use. This condition is associated with reactive oxygen species (ROS), resulting in various muscular disorders. We acquired 2D and 3D images using micro-computed tomography in gastrocnemius and soleus muscles of sciatic-denervated mice. We confirmed that sciatic denervation-small animal model reduced muscle volume. However, the intraperitoneal injection of Oenothera odorata root extract (EVP) delayed muscle atrophy compared to a control group. We also investigated the mechanism of muscle atrophy's relationship with ROS. EVP suppressed expression of SOD1, and increased expression of HSP70, in both H2O2-treated C2C12 myoblasts and sciatic-denervated mice. Moreover, EVP regulated apoptotic signals, including caspase-3, Bax, Bcl-2, and ceramide. These results indicate that EVP has a positive effect on reducing the effect of ROS on muscle atrophy.

  18. Atrophy of the brachialis muscle after a displaced clavicle fracture in an Ironman triathlete: case report

    Directory of Open Access Journals (Sweden)

    Knechtle Patrizia

    2011-10-01

    Full Text Available Abstract Clavicle fractures are frequent injuries in athletes and midshaft clavicle fractures in particular are well-known injuries in Ironman triathletes. In 2000, Auzou et al. described the mechanism leading to an isolated truncular paralysis of the musculocutaneous nerve after a shoulder trauma. It is well-known that nerve palsies can lead to an atrophy of the associated muscle if they persist for months or even longer. In this case report we describe a new case of an Ironman triathlete suffering from a persistent isolated atrophy of the brachialis muscle. The atrophy occurred following a displaced midshaft clavicle fracture acquiring while falling off his bike after hitting a duck during a competition.

  19. Reversal of muscle atrophy by Zhimu and Huangbai herb pair via activation of IGF-1/Akt and autophagy signal in cancer cachexia.

    Science.gov (United States)

    Zhuang, Pengwei; Zhang, Jinbao; Wang, Yan; Zhang, Mixia; Song, Lili; Lu, Zhiqiang; Zhang, Lu; Zhang, Fengqi; Wang, Jing; Zhang, Yanjun; Wei, Hongjun; Li, Hongyan

    2016-03-01

    Muscle atrophy is the prominent clinical feature of cancer-induced cachexia. Zhimu and Huangbai herb pair (ZBHP) has been used since ancient China times and have been phytochemically investigated for constituents that might cause anti-cancer, diabetes, and their complication. In this study, the effects and mechanisms of ZBHP on reversal of muscle atrophy were explored. C57BL/6 mice implanted with colon-26 adenocarcinoma were chosen to develop cancer cachexia for evaluating the effects of ZBHP on reversal of muscle atrophy. The body weight, survival time, inflammatory cytokines, and pathological changes of muscle were monitored. In addition, IGF-1/Akt and autophagy pathway members were analyzed to interpret the mechanism of drug response. The function and morphology of skeletal muscle in cachexia model were significantly disturbed, and the survival time was shortened. Consistently, inflammatory cytokines and muscle atrophy-related atrogin-1, MuRF1, and FOXO3 were significantly increased, and IGF-1/Akt and autophagy signal pathways were depressed. Treatment with ZBHP significantly alleviated tumor-free body weight reduction and cachexia-induced changes in cytokines and prolonged survival. ZBHP treatment not only inhibited the muscle atrophy-related genes but also activated the IGF-1/Akt and autophagy signal pathways to facilitate the protein synthesis. The results revealed that ZBHP treatment could inhibit the muscle atrophy induced by cancer cachexia and prolong the survival time, and ZBHP may be of value as a pharmacological alternative in treatment of cancer cachexia.

  20. Rotator cuff muscle degeneration and tear severity related to myogenic, adipogenic, and atrophy genes in human muscle.

    Science.gov (United States)

    Shah, Shivam A; Kormpakis, Ioannis; Cavinatto, Leonardo; Killian, Megan L; Thomopoulos, Stavros; Galatz, Leesa M

    2017-12-01

    Large rotator cuff tear size and advanced muscle degeneration can affect reparability of tears and compromise tendon healing. Clinicians often rely on direct measures of rotator cuff tear size and muscle degeneration from magnetic resonance imaging (MRI) to determine whether the rotator cuff tear is repairable. The objective of this study was to identify the relationship between gene expression changes in rotator cuff muscle degeneration to standard data available to clinicians. Radiographic assessment of preoperative rotator cuff tear severity was completed for 25 patients with varying magnitudes of rotator cuff tears. Tear width and retraction were measured using MRI, and Goutallier grade, tangent (tan) sign, and Thomazeau grade were determined. Expression of myogenic-, adipogenic-, atrophy-, and metabolism-related genes in biopsied muscles were correlated with tear width, tear retraction, Goutallier grade, tan sign, and Thomazeau grade. Tear width positively correlated with Goutallier grade in both the supraspinatus (r = 0.73) and infraspinatus (r = 0.77), along with tan sign (r = 0.71) and Thomazeau grade (r = 0.68). Decreased myogenesis (Myf5), increased adipogenesis (CEBPα, Lep, Wnt10b), and decreased metabolism (PPARα) correlated with radiographic assessments. Gene expression changes suggest that rotator cuff tears lead to a dramatic molecular response in an attempt to maintain normal muscle tissue, increase adipogenesis, and decrease metabolism. Fat accumulation and muscle atrophy appear to stem from endogenous changes rather than from changes mediated by infiltrating cells. Results suggest that chronic unloading of muscle, induced by rotator cuff tear, disrupts muscle homeostasis. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2808-2814, 2017. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

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

    Science.gov (United States)

    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

  2. Molecular mechanisms of obesity induced osteoporosis and muscle atrophy: A Review

    Directory of Open Access Journals (Sweden)

    Bipradas Roy

    2016-09-01

    Full Text Available Obesity and osteoporosis are two alarming health disorders prominent among middle and old age populations, and the numbers of those affected by these two disorders are increasing. It is estimated that more than 600 million adults are obese and over 200 million people have osteoporosis worldwide. Interestingly, both of these abnormalities share some common features including a genetic predisposition, and a common origin: bone marrow mesenchymal stromal cells. Obesity is characterized by the expression of leptin, adiponectin, interleukin 6 (IL-6, interleukin 10 (IL-10, monocyte chemotactic protein-1 (MCP-1, tumor necrosis factor-alpha (TNF-α, macrophage colony stimulating factor (M-CSF, growth hormone (GH, parathyroid hormone (PTH, angiotensin II (Ang II, 5-hydroxy-tryptamine (5-HT, Advance glycation end products (AGE, and myostatin, which exert their effects by modulating the signaling pathways within bone and muscle. Chemical messengers (eg. TNF-α, IL-6, AGE, leptins that are upregulated or downregulated as a result of obesity have been shown to act as negative regulators of osteoblasts, osteocytes and muscles, as well as positive regulators of osteoclasts. These additive effects of obesity ultimately increase the risk for osteoporosis and muscle atrophy. The aim of this review is to identify the potential cellular mechanisms through which obesity may facilitate osteoporosis, muscle atrophy and bone fractures.

  3. Reversal of muscle atrophy by Zhimu-Huangbai herb-pair via Akt/mTOR/FoxO3 signal pathway in streptozotocin-induced diabetic mice.

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    Jinbao Zhang

    Full Text Available Skeletal muscle atrophy is one of the serious complications of diabetes. Zhimu-Huangbai herb-pair (ZB is widely used in Chinese traditional medicine formulas for treating Xiaoke (known as diabetes and its complications. However, the effect of ZB on reversal of muscle atrophy and the underlying mechanisms remain unknown. In this research, we investigated the effect and possible mechanisms of ZB on skeletal muscle atrophy in diabetic mice. Animal model of diabetic muscle atrophy was developed by high fat diet (HFD feeding plus streptozotocin (STZ injection. After oral adminstration of ZB for 6 weeks, the effects of ZB on reversal of muscle atrophy and the underlying mechanisms were evaluated by biochemical, histological and western blot methods. The skeletal muscle weight, strength, and cross-sectional area of diabetic mice were significantly increased by ZB treatment. Biochemical results showed that ZB treatment reduced the serum glucose level, and elevated the serum insulin-like growth factor 1 (IGF-1 and insulin levels significantly compared with untreated diabetic group. The western blot results showed that ZB activated the mTOR signal pathway, shown as increased phosphorylations (p- of Akt, mTOR, Raptor, S6K1 and reduced Foxo3 expression compared with the model group. ZB could reverse muscle atrophy in diabetic mice. This may be through activation of mTOR signaling pathway that promotes protein synthesis, and inactivation foxo3 protein that inhibits protein degradation. These findings suggested that ZB may be considered as a potential candidate drug in treatment of diabetic muscle atrophy.

  4. Calcineurin signaling and PGC-1alpha expression are suppressed during muscle atrophy due to diabetes.

    Science.gov (United States)

    Roberts-Wilson, Tiffany K; Reddy, Ramesh N; Bailey, James L; Zheng, Bin; Ordas, Ronald; Gooch, Jennifer L; Price, S Russ

    2010-08-01

    PGC-1alpha is a transcriptional coactivator that controls energy homeostasis through regulation of glucose and oxidative metabolism. Both PGC-1alpha expression and oxidative capacity are decreased in skeletal muscle of patients and animals undergoing atrophy, suggesting that PGC-1alpha participates in the regulation of muscle mass. PGC-1alpha gene expression is controlled by calcium- and cAMP-sensitive pathways. However, the mechanism regulating PGC-1alpha in skeletal muscle during atrophy remains unclear. Therefore, we examined the mechanism responsible for decreased PGC-1alpha expression using a rodent streptozotocin (STZ) model of chronic diabetes and atrophy. After 21days, the levels of PGC-1alpha protein and mRNA were decreased. We examined the activation state of CREB, a potent activator of PGC-1alpha transcription, and found that phospho-CREB was paradoxically high in muscle of STZ-rats, suggesting that the cAMP pathway was not involved in PGC-1alpha regulation. In contrast, expression of calcineurin (Cn), a calcium-dependent phosphatase, was suppressed in the same muscles. PGC-1alpha expression is regulated by two Cn substrates, MEF2 and NFATc. Therefore, we examined MEF2 and NFATc activity in muscles from STZ-rats. Target genes MRF4 and MCIP1.4 mRNAs were both significantly reduced, consistent with reduced Cn signaling. Moreover, levels of MRF4, MCIP1.4, and PGC-1alpha were also decreased in muscles of CnAalpha-/- and CnAbeta-/- mice without diabetes indicating that decreased Cn signaling, rather than changes in other calcium- or cAMP-sensitive pathways, were responsible for decreased PGC-1alpha expression. These findings demonstrate that Cn activity is a major determinant of PGC-1alpha expression in skeletal muscle during diabetes and possibly other conditions associated with loss of muscle mass.

  5. Calcineurin signaling and PGC-1α expression are suppressed during muscle atrophy due to diabetes

    Science.gov (United States)

    Roberts-Wilson, Tiffany K.; Reddy, Ramesh N.; Bailey, James L.; Zheng, Bin; Ordas, Ronald; Gooch, Jennifer L.; Price, S. Russ

    2010-01-01

    PGC-1α is a transcriptional coactivator that controls energy homeostasis through regulation of glucose and oxidative metabolism. Both PGC-1α expression and oxidative capacity are decreased in skeletal muscle of patients and animals undergoing atrophy, suggesting that PGC-1α participates in the regulation of muscle mass. PGC-1α gene expression is controlled by calcium- and cAMP-sensitive pathways. However, the mechanism regulating PGC-1α in skeletal muscle during atrophy remains unclear. Therefore, we examined the mechanism responsible for decreased PGC-1α expression using a rodent streptozotocin (STZ) model of chronic diabetes and atrophy. After 21d, the levels of PGC-1α protein and mRNA were decreased. We examined the activation state of CREB, a potent activator of PGC-1α transcription, and found that phospho-CREB was paradoxically high in muscle of STZ-rats, suggesting that the cAMP pathway was not involved in PGC-1α regulation. In contrast, expression of calcineurin (Cn), a calcium-dependent phosphatase, was suppressed in the same muscles. PGC-1α expression is regulated by two Cn substrates, MEF2 and NFATc. Therefore, we examined MEF2 and NFATc activity in muscles from STZ-rats. Target genes MRF4 and MCIP1.4 were both significantly reduced, consistent with reduced Cn signaling. Moreover, levels of MRF4, MCIP1.4, and PGC-1α were also decreased in muscles of CnAα-/- and CnAβ-/- mice without diabetes indicating that decreased Cn signaling, rather than changes in other calcium- or cAMP-sensitive pathways, were responsible for decreased PGC-1α expression. These findings demonstrate that Cn activity is a major determinant of PGC-1α expression in skeletal muscle during diabetes and possibly other conditions associated with loss of muscle mass. PMID:20359506

  6. Atrophy of foot muscles in diabetic patients can be detected with ultrasonography

    DEFF Research Database (Denmark)

    Severinsen, Kaare; Obel, Annette; Jakobsen, Johannes

    2007-01-01

    OBJECTIVE: To establish a bedside test with ultrasonography for evaluation of foot muscle atrophy in diabetic patients. RESEARCH DESIGN AND METHODS: Thickness and cross-sectional area (CSA) of the extensor digitorum brevis muscle (EDB) and of the muscles of the first interstitium (MILs) were...... determined in 26 diabetic patients and in 26 matched control subjects using ultrasonography. To estimate the validity, findings were related to the total volume of all foot muscles determined at magnetic resonance imaging (MRI-FM(vol)). Furthermore, the relations of ultrasonographic estimates to nerve...... than in nonneuropathic diabetic patients (5.8 +/- 2.1 vs. 7.5 +/- 1.7 mm [P foot muscles determined at ultrasonography is directly related to foot muscle volume determined by MRI and to various...

  7. Muscle atrophy as a consequence of rotator cuff tears: should we compare the muscles of the rotator cuff with those of the deltoid?

    Energy Technology Data Exchange (ETDEWEB)

    Ashry, Reem; Schweitzer, Mark E.; Cunningham, Patricia; Cohen, Jodi; Babb, James; Cantos, Andrew [Hospital for Joint Diseases, NYU Medical Center, Department of Radiology, New York, NY (United States)

    2007-09-15

    The quantitative assessment of muscle atrophy has a degree of importance in prognosticating rotator cuff treatment. However, it has been conjectured that muscle fat increases with aging. Therefore, we thought that the quantitative assessment of the supraspinatous would be better if made in comparison with a standard of reference such as the deltoid. Consequently, we performed a two-part study, first evaluating supraspinatous changes compared with the deltoid in ''normals'' with aging, and second, determining if in patients with cuff tears the supraspinatous fat exceeds that of the deltoid. In part 1, we studied 50 patients stratified by decade. In the first sitting, two blinded independent observers quantitatively graded the deltoid (with the supraspinatous obscured) and in the second sitting the same two observers quantitatively graded the supraspinatous (with the deltoid obscured). In part 2 of the study, we evaluated patients with moderate rotator cuff tears (>2 cm) and performed the same blinded, two-sitting, quantitative assessment (with the comparison muscle obscured). We found that muscle atrophy increases with age in patients without tears (0.011/0.028 U/year), although to a greater degree in the deltoid (p = 0.032). Also, in similarly aged patients, quantitative scores of the deltoid closely matched those of the supraspinatous (p = 0.071). Notably, however, in patients with large tears, the supraspinatous showed significant changes disproportionate to those of the deltoid, regardless of patient age (p = 0.044). In the presence of a normal rotator cuff, fatty infiltration increases with age. Age-related changes occur more frequently in the deltoid, verifying this muscle's potential as a standard of reference. With cuff tears, supraspinatous atrophy was disproportionate to that of the deltoid. Therefore, systematic assessment of supraspinatous muscle atrophy may be more reliable using the deltoid as a control for comparison than

  8. Muscle atrophy as a consequence of rotator cuff tears: should we compare the muscles of the rotator cuff with those of the deltoid?

    International Nuclear Information System (INIS)

    Ashry, Reem; Schweitzer, Mark E.; Cunningham, Patricia; Cohen, Jodi; Babb, James; Cantos, Andrew

    2007-01-01

    The quantitative assessment of muscle atrophy has a degree of importance in prognosticating rotator cuff treatment. However, it has been conjectured that muscle fat increases with aging. Therefore, we thought that the quantitative assessment of the supraspinatous would be better if made in comparison with a standard of reference such as the deltoid. Consequently, we performed a two-part study, first evaluating supraspinatous changes compared with the deltoid in ''normals'' with aging, and second, determining if in patients with cuff tears the supraspinatous fat exceeds that of the deltoid. In part 1, we studied 50 patients stratified by decade. In the first sitting, two blinded independent observers quantitatively graded the deltoid (with the supraspinatous obscured) and in the second sitting the same two observers quantitatively graded the supraspinatous (with the deltoid obscured). In part 2 of the study, we evaluated patients with moderate rotator cuff tears (>2 cm) and performed the same blinded, two-sitting, quantitative assessment (with the comparison muscle obscured). We found that muscle atrophy increases with age in patients without tears (0.011/0.028 U/year), although to a greater degree in the deltoid (p 0.032). Also, in similarly aged patients, quantitative scores of the deltoid closely matched those of the supraspinatous (p = 0.071). Notably, however, in patients with large tears, the supraspinatous showed significant changes disproportionate to those of the deltoid, regardless of patient age (p = 0.044). In the presence of a normal rotator cuff, fatty infiltration increases with age. Age-related changes occur more frequently in the deltoid, verifying this muscle's potential as a standard of reference. With cuff tears, supraspinatous atrophy was disproportionate to that of the deltoid. Therefore, systematic assessment of supraspinatous muscle atrophy may be more reliable using the deltoid as a control for comparison than assessing it in isolation

  9. Age and sex-based distribution of lumbar multifidus muscle atrophy and coexistence of disc hernia: an MRI study of 2028 patients.

    Science.gov (United States)

    Ekin, Elif Evrim; Kurtul Yıldız, Hülya; Mutlu, Harun

    2016-01-01

    We aimed to investigate the prevalence of lumbar multifidus muscle (LMM) atrophy in patients having mechanical low back pain with and without disc hernia. In total, 2028 lumbar magnetic resonance imaging scans of low back pain patients (age range, 18-88 years) were re-evaluated retrospectively. LMM atrophy was visually assessed in axial sections of L4-L5 and L5-S1 levels. LMM atrophy prevalence at both levels was significantly higher in subjects ≥40 years compared with younger adults (P hernia, LMM atrophy was significantly more frequent than normal muscle (n=559 vs. n=392; P disc hernia was 13%. Hernia was more frequent in patients with LMM atrophy compared with patients without atrophy (P disc hernia is found more frequently in individuals with LMM atrophy.

  10. Smad3 induces atrogin-1, inhibits mTOR and protein synthesis, and promotes muscle atrophy in vivo.

    Science.gov (United States)

    Goodman, Craig A; McNally, Rachel M; Hoffmann, F Michael; Hornberger, Troy A

    2013-11-01

    Myostatin, a member of the TGF superfamily, is sufficient to induce skeletal muscle atrophy. Myostatin-induced atrophy is associated with increases in E3-ligase atrogin-1 expression and protein degradation and decreases in Akt/mechanistic target of rapamycin (mTOR) signaling and protein synthesis. Myostatin signaling activates the transcription factor Smad3 (Small Mothers Against Decapentaplegic), which has been shown to be necessary for myostatin-induced atrogin-1 expression and atrophy; however, it is not known whether Smad3 is sufficient to induce these events or whether Smad3 simply plays a permissive role. Thus, the aim of this study was to address these questions with an in vivo model. To accomplish this goal, in vivo transfection of plasmid DNA was used to create transient transgenic mouse skeletal muscles, and our results show for the first time that Smad3 expression is sufficient to stimulate atrogin-1 promoter activity, inhibit Akt/mTOR signaling and protein synthesis, and induce muscle fiber atrophy. Moreover, we propose that Akt/mTOR signaling is inhibited by a Smad3-induced decrease in microRNA-29 (miR-29) expression and a subsequent increase in the translation of phosphatase and tensin homolog (PTEN) mRNA. Smad3 is also sufficient to inhibit peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α) promoter activity and to increase FoxO (Forkhead Box Protein, Subclass O)-mediated signaling and the promoter activity of plasminogen activator inhibitor 1 (PAI-1). Combined, this study provides the first evidence that Smad3 is sufficient to regulate many of the events associated with myostatin-induced atrophy and therefore suggests that Smad3 signaling may be a viable target for therapies aimed at preventing myostatin-induced muscle atrophy.

  11. N-myristoylated ubiquitin ligase Cbl-b inhibitor prevents on glucocorticoid-induced atrophy in mouse skeletal muscle.

    Science.gov (United States)

    Ochi, Arisa; Abe, Tomoki; Nakao, Reiko; Yamamoto, Yoriko; Kitahata, Kanako; Takagi, Marina; Hirasaka, Katsuya; Ohno, Ayako; Teshima-Kondo, Shigetada; Taesik, Gwag; Choi, Inho; Kawamura, Tomoyuki; Nemoto, Hisao; Mukai, Rie; Terao, Junji; Nikawa, Takeshi

    2015-03-15

    A DGpYMP peptide mimetic of tyrosine(608)-phosphorylated insulin receptor substrate-1 (IRS-1), named Cblin, was previously shown to significantly inhibit Cbl-b-mediated IRS-1 ubiquitination. In the present study, we developed N-myristoylated Cblin and investigated whether it was effective in preventing glucocorticoid-induced muscle atrophy. Using HEK293 cells overexpressing Cbl-b, IRS-1 and ubiquitin, we showed that the 50% inhibitory concentrations of Cbl-b-mediated IRS-1 ubiquitination by N-myristoylated Cblin and Cblin were 30 and 120 μM, respectively. Regarding the DEX-induced atrophy of C2C12 myotubes, N-myristoylated Cblin was more effective than Cblin for inhibiting the DEX-induced decreases in C2C12 myotube diameter and IRS-1 degradation. The inhibitory efficacy of N-myristoylated Cblin on IRS-1 ubiquitination in C2C12 myotubes was approximately fourfold larger than that of Cblin. Furthermore, N-myristoylation increased the incorporation of Cblin into HEK293 cells approximately 10-folds. Finally, we demonstrated that N-myristoylated Cblin prevented the wet weight loss, IRS-1 degradation, and MAFbx/atrogin-1 and MuRF-1 expression in gastrocnemius muscle of DEX-treated mice approximately fourfold more effectively than Cblin. Taken together, these results suggest that N-myristoylated Cblin prevents DEX-induced skeletal muscle atrophy in vitro and in vivo, and that N-myristoylated Cblin more effectively prevents muscle atrophy than unmodified Cblin. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. The effect of exercise hypertrophy and disuse atrophy on muscle contractile properties: a mechanomyographic analysis.

    Science.gov (United States)

    Than, Christian; Tosovic, Danijel; Seidl, Laura; Mark Brown, J

    2016-12-01

    To determine whether mechanomyographic (MMG) determined contractile properties of the biceps brachii change during exercise-induced hypertrophy and subsequent disuse atrophy. Healthy subjects (mean ± SD, 23.7 ± 2.6 years, BMI 21.8 ± 2.4, n = 19) performed unilateral biceps curls (9 sets × 12 repetitions, 5 sessions per week) for 8 weeks (hypertrophic phase) before ceasing exercise (atrophic phase) for the following 8 weeks (non-dominant limb; treatment, dominant limb; control). MMG measures of muscle contractile properties (contraction time; T c , maximum displacement; D max , contraction velocity; V c ), electromyographic (EMG) measures of muscle fatigue (median power frequency; MPF), strength measures (maximum voluntary contraction; MVC) and measures of muscle thickness (ultrasound) were obtained. Two-way repeated measures ANOVA showed significant differences (P muscle thickness was greater than control, reflecting gross hypertrophy. MMG variables Dmax (weeks 2, 7) and Vc (weeks 7, 8) declined. During the atrophic phase, MVC (weeks 9-12) and muscle thickness (weeks 9, 10) initially remained high before declining to control levels, reflecting gross atrophy. MMG variables D max (weeks 9, 14) and V c (weeks 9, 14, 15) also declined during the atrophic phase. No change in T c was found throughout the hypertrophic or atrophic phases. MMG detects changes in contractile properties during stages of exercise-induced hypertrophy and disuse atrophy suggesting its applicability as a clinical tool in musculoskeletal rehabilitation.

  13. Aerobic exercise training prevents heart failure-induced skeletal muscle atrophy by anti-catabolic, but not anabolic actions.

    Directory of Open Access Journals (Sweden)

    Rodrigo W A Souza

    Full Text Available Heart failure (HF is associated with cachexia and consequent exercise intolerance. Given the beneficial effects of aerobic exercise training (ET in HF, the aim of this study was to determine if the ET performed during the transition from cardiac dysfunction to HF would alter the expression of anabolic and catabolic factors, thus preventing skeletal muscle wasting.We employed ascending aortic stenosis (AS inducing HF in Wistar male rats. Controls were sham-operated animals. At 18 weeks after surgery, rats with cardiac dysfunction were randomized to 10 weeks of aerobic ET (AS-ET or to an untrained group (AS-UN. At 28 weeks, the AS-UN group presented HF signs in conjunction with high TNF-α serum levels; soleus and plantaris muscle atrophy; and an increase in the expression of TNF-α, NFκB (p65, MAFbx, MuRF1, FoxO1, and myostatin catabolic factors. However, in the AS-ET group, the deterioration of cardiac function was prevented, as well as muscle wasting, and the atrophy promoters were decreased. Interestingly, changes in anabolic factor expression (IGF-I, AKT, and mTOR were not observed. Nevertheless, in the plantaris muscle, ET maintained high PGC1α levels.Thus, the ET capability to attenuate cardiac function during the transition from cardiac dysfunction to HF was accompanied by a prevention of skeletal muscle atrophy that did not occur via an increase in anabolic factors, but through anti-catabolic activity, presumably caused by PGC1α action. These findings indicate the therapeutic potential of aerobic ET to block HF-induced muscle atrophy by counteracting the increased catabolic state.

  14. Will Preoperative Atrophy and Fatty Degeneration of the Shoulder Muscles Improve after Rotator Cuff Repair in Patients with Massive Rotator Cuff Tears?

    Directory of Open Access Journals (Sweden)

    Hiroshi Yamaguchi

    2012-01-01

    Full Text Available Recently, retear rate after repair for massive cuff tear have been improved through devised suture techniques. However, reported retear rate is relevant to preoperative atrophy and fatty degeneration. The purpose of this study was to investigate whether preoperative atrophy and fatty degeneration of rotator cuff muscles improve by successful repair. Twenty-four patients with massive rotator cuff tear were evaluated on the recovery of atrophy and fatty degeneration of supraspinatus and infraspinatus muscle after surgery. Atrophy was classified by the occupation ratio and fatty degeneration by modified Goutallier's classification. Both were assessed on magnetic resonance imaging (MRI before and after the operation. When the cuff was well repaired, improvement of the atrophy and fatty degeneration were observed in a half and a one-fourth of the cases, respectively. In retear cases, however, atrophy and fatty degeneration became worse. Improvement of atrophy and fatty degeneration of the rotator cuff muscles may be expected in the cases with successful achievement of rotator cuff repair for large and massive tear.

  15. Reversibility of Supraspinatus Muscle Atrophy in Tendon-Bone Healing After Arthroscopic Rotator Cuff Repair.

    Science.gov (United States)

    Park, Yong Bok; Ryu, Ho Young; Hong, Jin Ho; Ko, Young Hoo; Yoo, Jae Chul

    2016-04-01

    To date, there are few reports of the definite reversibility of rotator cuff muscle atrophy after repair. To evaluate the reversibility of rotator cuff muscle atrophy after successful arthroscopic repair. Case series; Level of evidence, 4. Included in this study were 47 patients (mean age, 61.2 ± 7.3 years; range, 49-73 years) who underwent arthroscopic rotator cuff repair as well as magnetic resonance imaging (MRI) preoperatively and at 6-month and last follow-up. Patients who had confirmed rotator cuff healing (grades 1-3 according to the Sugaya classification) on both series of postoperative MRI were enrolled in the study. The mean time from the onset of symptoms to surgery was 24.7 ± 25.6 months (range, 3-120 months). The minimum follow-up was 2 years, and the mean follow-up duration was 41.8 ± 14.4 months. Serial changes in the supraspinatus muscle area on the most matching MRI scans (sagittal-oblique view) were evaluated. The area was measured by 2 independent observers. Both independent observers reported no significant difference in the area of the supraspinatus muscle between the preoperative time point and 6-month follow-up (observer 1: P = .135; observer 2: P = .189). However, there was a significant difference between the 6-month and last follow-up (mean, 41.8 months; observers 1 and 2: P .999) or from 6-month to final follow-up (P = .077). After successful arthroscopic rotator cuff repair, there was a slight (11.3%-13.9%) increase in muscle volume from preoperatively to final follow-up, as seen on serial MRI. Fatty infiltration according to the Goutallier grade was not reversed (P = .077). Some reversibility of supraspinatus muscle atrophy may exist in tendon-bone healing after arthroscopic rotator cuff repair; further follow-up is needed to better elucidate this result. © 2016 The Author(s).

  16. Relationship between Lower Motor Neuron Atrophy and Wei Syndrome in Su Wen%下运动神经元瘫与《素问》痿病相关性分析

    Institute of Scientific and Technical Information of China (English)

    唐东一

    2016-01-01

    The clinical manifestations of the lower motor neuron atrophy are muscle weakness ,muscle atro-phy and fasciculation. They are similar to the wei disease described in Su Wen Wei Lun,which manifests as weak feet,claw dry and muscle tremor. Actually the muscle tremor is fasciculation,not the weakness and flaccidity of the muscles. Wei disease includes motor neuron disease or other lower motor neuron paralysis disease of the modern medicine,but not includes the upper motor neuron paralysis and muscle atrophy myo-genic disease. According to the theory that “treatment of atrophy should be focused on yangming channel”, invigrating spleen and tonifying stomach could achieve satisfactory effects.%下运动神经元瘫临床表现的肌无力、肌萎缩和肌束震颤与《素问·痿论》所述痿病之足痿不用、爪枯、肉蠕动相似。肉蠕动是指肌束颤动,而非肌肉软弱无力。根据临床表现,痿病应包含现代医学的运动神经元病或其他下运动神经元瘫痪性疾病,而不包含上运动神经元瘫和肌源性肌萎缩疾病。根据“治痿独取阳明”的理论,应用健脾养胃法治疗此类疾病效果较好。

  17. Green tea extracts ameliorate high-fat diet-induced muscle atrophy in senescence-accelerated mouse prone-8 mice.

    Science.gov (United States)

    Onishi, Shintaro; Ishino, Mayu; Kitazawa, Hidefumi; Yoto, Ai; Shimba, Yuki; Mochizuki, Yusuke; Unno, Keiko; Meguro, Shinichi; Tokimitsu, Ichiro; Miura, Shinji

    2018-01-01

    Muscle atrophy (loss of skeletal muscle mass) causes progressive deterioration of skeletal function. Recently, excessive intake of fats was suggested to induce insulin resistance, followed by muscle atrophy. Green tea extracts (GTEs), which contain polyphenols such as epigallocatechin gallate, have beneficial effects on obesity, hyperglycemia, and insulin resistance, but their effects against muscle atrophy are still unclear. Here, we found that GTEs prevented high-fat (HF) diet-induced muscle weight loss in senescence-accelerated mouse prone-8 (SAMP8), a murine model of senescence. SAMP8 mice were fed a control diet, an HF diet, or HF with 0.5% GTEs (HFGT) diet for 4 months. The HF diet induced muscle weight loss with aging (measured as quadriceps muscle weight), whereas GTEs prevented this loss. In HF diet-fed mice, blood glucose and plasma insulin concentrations increased in comparison with the control group, and these mice had insulin resistance as determined by homeostasis model assessment of insulin resistance (HOMA-IR). In these mice, serum concentrations of leukocyte cell-derived chemotaxin 2 (LECT2), which is known to induce insulin resistance in skeletal muscle, were elevated, and insulin signaling in muscle, as determined by the phosphorylation levels of Akt and p70 S6 kinases, tended to be decreased. In HFGT diet-fed mice, these signs of insulin resistance and elevation of serum LECT2 were not observed. Although our study did not directly show the effect of serum LECT2 on muscle weight, insulin resistance examined using HOMA-IR indicated an intervention effect of serum LECT2 on muscle weight, as revealed by partial correlation analysis. Accordingly, GTEs might have beneficial effects on age-related and HF diet-induced muscle weight loss, which correlates with insulin resistance and is accompanied by a change in serum LECT2.

  18. Isoform-Specific Na,K-ATPase Alterations Precede Disuse-Induced Atrophy of Rat Soleus Muscle

    Directory of Open Access Journals (Sweden)

    Violetta V. Kravtsova

    2015-01-01

    Full Text Available This study examines the isoform-specific effects of short-term hindlimb suspension (HS on the Na,K-ATPase in rat soleus muscle. Rats were exposed to 24–72 h of HS and we analyzed the consequences on soleus muscle mass and contractile parameters; excitability and the resting membrane potential (RMP of muscle fibers; the electrogenic activity, protein, and mRNA content of the α1 and α2 Na,K-ATPase; the functional activity and plasma membrane localization of the α2 Na,K-ATPase. Our results indicate that 24–72 h of HS specifically decreases the electrogenic activity of the Na,K-ATPase α2 isozyme and the RMP of soleus muscle fibers. This decrease occurs prior to muscle atrophy or any change in contractile parameters. The α2 mRNA and protein content increased after 24 h of HS and returned to initial levels at 72 h; however, even the increased content was not able to restore α2 enzyme activity in the disused soleus muscle. There was no change in the membrane localization of α2 Na,K-ATPase. The α1 Na,K-ATPase electrogenic activity, protein and mRNA content did not change. Our findings suggest that skeletal muscle use is absolutely required for α2 Na,K-ATPase transport activity and provide the first evidence that Na,K-ATPase alterations precede HS-induced muscle atrophy.

  19. An MRI study on the relations between muscle atrophy, shoulder function and glenohumeral deformity in shoulders of children with obstetric brachial plexus injury

    Directory of Open Access Journals (Sweden)

    van Doorn-Loogman Mirjam H

    2009-05-01

    Full Text Available Abstract Background A substantial number of children with an obstetric brachial plexus lesion (OBPL will develop internal rotation adduction contractures of the shoulder, posterior humeral head subluxations and glenohumeral deformities. Their active shoulder function is generally limited and a recent study showed that their shoulder muscles were atrophic. This study focuses on the role of shoulder muscles in glenohumeral deformation and function. Methods This is a prospective study on 24 children with unilateral OBPL, who had internal rotation contractures of the shoulder (mean age 3.3 years, range 14.7 months to 7.3 years. Using MR imaging from both shoulders the following parameters were assessed: glenoid form, glenoscapular angle, subluxation of the humeral head, thickness and segmental volume of the subscapularis, infraspinatus and deltoid muscles. Shoulder function was assessed measuring passive external rotation of the shoulder and using the Mallet score for active function. Statistical tests used are t-tests, Spearman's rho, Pearsons r and logistic regression. Results The affected shoulders showed significantly reduced muscle sizes, increased glenoid retroversion and posterior subluxation. Mean muscle size compared to the normal side was: subscapularis 51%, infraspinatus 61% and deltoid 76%. Glenoid form was related to infraspinatus muscle atrophy. Subluxation was related to both infraspinatus and subscapularis atrophy. There was no relation between atrophy of muscles and passive external rotation. Muscle atrophy was not related to the Mallet score or its dimensions. Conclusion Muscle atrophy was more severe in the subscapularis muscle than in infraspinatus and deltoid. As the muscle ratios are not related to passive external rotation nor to active function of the shoulder, there must be other muscle properties influencing shoulder function.

  20. Effect of early implementation of electrical muscle stimulation to prevent muscle atrophy and weakness in patients after anterior cruciate ligament reconstruction.

    Science.gov (United States)

    Hasegawa, Satoshi; Kobayashi, Masahiko; Arai, Ryuzo; Tamaki, Akira; Nakamura, Takashi; Moritani, Toshio

    2011-08-01

    Following anterior cruciate ligament (ACL) reconstruction, restricted weight bearing and immobilization results in thigh and calf muscle atrophy and weakness. The purpose of this study was to assess the effect of electrical muscle stimulation (EMS) on prevention of muscle atrophy in patients during the early rehabilitation stage after ACL reconstruction. Twenty patients with acute ACL tears were divided into two groups randomly. The control group (CON group) participated in only the usual rehabilitation program. In addition to this protocol, the electrical muscle stimulation group (EMS group) received EMS training using the wave form of 20 Hz exponential pulse from the 2nd post-operative day to 4 weeks after the surgery. Muscle thickness of vastus lateralis and calf increased significantly 4 weeks after surgery in the EMS group, while it decreased significantly in the CON group. The decline of knee extension strength was significantly less in the EMS group than in the CON group at 4 weeks after the surgery, and the EMS group showed greater recovery of knee extension strength at 3 months after surgery. EMS implemented during the early rehabilitation stage is effective in maintaining and increasing muscle thickness and strength in the operated limb. Copyright © 2011 Elsevier Ltd. All rights reserved.

  1. Effects of edaravone on muscle atrophy and locomotor function in patients with ischemic stroke: a randomized controlled pilot study.

    Science.gov (United States)

    Naritomi, Hiroaki; Moriwaki, Hiroshi; Metoki, Norifumi; Nishimura, Hiroyuki; Higashi, Yasuto; Yamamoto, Yasumasa; Yuasa, Hiroyuki; Oe, Hiroshi; Tanaka, Kortaro; Saito, Kozue; Terayama, Yasuo; Oda, Tadafumi; Tanahashi, Norio; Kondo, Hisao

    2010-01-01

    Stroke patients with severe leg paralysis are often bedridden in the acute and subacute phase, which increases the risk of disuse muscle atrophy in the chronic phase. The evidence to date indicates that oxidative stress plays an important role in the mechanism of disuse muscle atrophy. Therefore, the aim of this study was to determine if long-term radical scavenger treatment with edaravone following an acute stroke prevents the progression of disuse muscle atrophy and improves leg locomotor function in the chronic phase. This randomized controlled pilot study was conducted at 19 acute stroke and rehabilitation centers across Japan. Forty-seven ischemic stroke patients with at least leg motor weakness admitted within 24 hours of onset were randomly assigned to receive continuous intravenous infusions of edaravone 30 mg twice daily for 3 days (short-term group) or 10-14 days (long-term group). The primary endpoints of the study included the degree of leg disuse muscle atrophy, as measured by the percentage change from baseline in femoral muscle circumference 15 cm above the knee, and the improvement in leg locomotor function, as assessed by the maximum walking speed over 10 m, 3 months after the onset of stroke. Three-month follow-up was completed by a total of 41 patients (21 in the short-term group and 20 in the long-term group). On admission, there was no significant difference in the severity of stroke or the grade of leg paresis between the two treatment groups. The grade of disuse muscle atrophy and incidence of gait impairment 3 weeks after stroke onset were also similar between the short- and long-term groups. However, disuse muscle atrophy of the paretic and non-paretic legs was significantly less severe in the long-term versus the short-term treatment group (3.6 ± 5.9% and 1.5 ± 6.0% vs 8.3 ± 5.2% and 5.7 ± 6.4%; p < 0.01 and p < 0.05) 3 months after stroke onset. Additionally, the maximum walking speed over a distance of 10 m

  2. Abdominal rectus muscle atrophy and midline shift after colostomy creation.

    Science.gov (United States)

    Timmermans, Lucas; Deerenberg, Eva B; van Dijk, Sven M; Lamme, Bas; Koning, Anton H; Kleinrensink, Gert-Jan; Jeekel, Johannes; Lange, Johan F

    2014-04-01

    Incisional hernia (IH) can be attributed to multiple factors. The presence of a parastomal hernia has shown to be a risk factor for IH after midline laparotomy. Our hypothesis is that this increased risk of IH may be caused by changes in biomechanical forces, such as midline shift to the contralateral side of the colostomy owing to decreased restraining forces at the site of the colostomy, and left abdominal rectus muscle (ARM) atrophy owing to intercostal nerve damage. Patients were selected if they underwent end-colostomy via open operation between 2004 and 2011. Patients were eligible if computed tomography (CT) had been performed postoperatively. If available, preoperative CTs were collected for case-control analyses. Midline shift was measured using V-scope application in the I-space, a CAVE-like virtual reality system. For the ARM atrophy hypothesis, measurements of ARM were performed at the level of colostomy, and 3 and 8 cm cranial and caudal of the colostomy. Postoperative CT were available for 77 patients; of these patients, 30 also had a preoperative CT. Median follow-up was 19 months. A mean shift to the right side was identified after preoperative and postoperative comparison; from -1.3 ± 4.6 to 2.1 ± 9.3 (P = .043). Furthermore, during rectus muscle measurements, a thinner left ARM was observed below the level of colostomy. Creation of a colostomy alters the abdominal wall. Atrophy of the left ARM was seen caudal to the level of the colostomy, and a midline shift to the right side was evident on CT. These changes may explain the increased rate of IH after colostomy creation. Copyright © 2014 Mosby, Inc. All rights reserved.

  3. Calpain 3 Expression Pattern during Gastrocnemius Muscle Atrophy and Regeneration Following Sciatic Nerve Injury in Rats

    Directory of Open Access Journals (Sweden)

    Ronghua Wu

    2015-11-01

    Full Text Available Calpain 3 (CAPN3, also known as p94, is a skeletal muscle-specific member of the calpain family that is involved in muscular dystrophy; however, the roles of CAPN3 in muscular atrophy and regeneration are yet to be understood. In the present study, we attempted to explain the effect of CAPN3 in muscle atrophy by evaluating CAPN3 expression in rat gastrocnemius muscle following reversible sciatic nerve injury. After nerve injury, the wet weight ratio and cross sectional area (CSA of gastrocnemius muscle were decreased gradually from 1–14 days and then recovery from 14–28 days. The active form of CAPN3 (~62 kDa protein decreased slightly on day 3 and then increased from day 7 to 14 before a decrease from day 14 to 28. The result of linear correlation analysis showed that expression of the active CAPN3 protein level was negatively correlated with muscle wet weight ratio. CAPN3 knockdown by short interfering RNA (siRNA injection improved muscle recovery on days 7 and 14 after injury as compared to that observed with control siRNA treatment. Depletion of CAPN3 gene expression could promote myoblast differentiation in L6 cells. Based on these findings, we conclude that the expression pattern of the active CAPN3 protein is linked to muscle atrophy and regeneration following denervation: its upregulation during early stages may promote satellite cell renewal by inhibiting differentiation, whereas in later stages, CAPN3 expression may be downregulated to stimulate myogenic differentiation and enhance recovery. These results provide a novel mechanistic insight into the role of CAPN3 protein in muscle regeneration after peripheral nerve injury.

  4. Neck muscle atrophy and soft-tissue fibrosis after neck dissection and postoperative radiotherapy for oral cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jinu; Shin, Eun Seow; Kim, Jeong Eon; Yoon, Sang Pil [Jeju National University School of Medicine, Jeju (Korea, Republic of); Kim, Young Suk [Dept. of Radiation Oncology, Jeju National University Hospital, Jeju National University School of Medicine, Jeju (Korea, Republic of)

    2015-12-15

    Late complications of head and neck cancer survivors include neck muscle atrophy and soft-tissue fibrosis. We present an autopsy case of neck muscle atrophy and soft-tissue fibrosis (sternocleidomastoid, omohyoid, digastric, sternohyoid, sternothyroid, and platysma muscles) within the radiation field after modified radical neck dissection type I and postoperative radiotherapy for floor of mouth cancer. A 70-year-old man underwent primary tumor resection of the left floor of mouth, left marginal mandibulectomy, left modified radical neck dissection type I, and reconstruction with a radial forearm free flap. The patient received adjuvant radiotherapy. The dose to the primary tumor bed and involved neck nodes was 63 Gy in 35 fractions over 7 weeks. Areas of subclinical disease (left lower neck) received 50 Gy in 25 fractions over 5 weeks. Adjuvant chemotherapy was not administered.

  5. Inhibitors of the proteasome reduce the accelerated proteolysis in atrophying rat skeletal muscles.

    OpenAIRE

    Tawa, N E; Odessey, R; Goldberg, A L

    1997-01-01

    Several observations have suggested that the enhanced proteolysis and atrophy of skeletal muscle in various pathological states is due primarily to activation of the ubiquitin-proteasome pathway. To test this idea, we investigated whether peptide aldehyde inhibitors of the proteasome, N-acetyl-leucyl-leucyl-norleucinal (LLN), or the more potent CBZ-leucyl-leucyl-leucinal (MG132) suppressed proteolysis in incubated rat skeletal muscles. These agents (e.g., MG132 at 10 microM) inhibited nonlyso...

  6. Muscular hypertrophy and atrophy in normal rats provoked by the administration of normal and denervated muscle extracts.

    Science.gov (United States)

    Agüera, Eduardo; Castilla, Salvador; Luque, Evelio; Jimena, Ignacio; Leiva-Cepas, Fernando; Ruz-Caracuel, Ignacio; Peña, José

    2016-12-01

    This study was conducted to determine the effects of extracts obtained from both normal and denervated muscles on different muscle types. Wistar rats were used and were divided into a control group and four experimental groups. Each experimental group was treated intraperitoneally during 10 consecutive days with a different extract. These extracts were obtained from normal soleus muscle, denervated soleus, normal extensor digitorum longus, and denervated extensor digitorum longus. Following treatment, the soleus and extensor digitorum longus muscles were obtained for study under optic and transmission electron microscope; morphometric parameters and myogenic responses were also analyzed. The results demonstrated that the treatment with normal soleus muscle and denervated soleus muscle extracts provoked hypertrophy and increased myogenic activity. In contrast, treatment with extracts from the normal and denervated EDL had a different effect depending on the muscle analyzed. In the soleus muscle it provoked hypertrophy of type I fibers and increased myogenic activity, while in the extensor digitorum longus atrophy of the type II fibers was observed without changes in myogenic activity. This suggests that the muscular responses of atrophy and hypertrophy may depend on different factors related to the muscle type which could be related to innervation.

  7. Invited review: Genetics and claw health: Opportunities to enhance claw health by genetic selection

    Science.gov (United States)

    Routine recording of claw health status at claw trimming of dairy cattle have been established in several countries, providing valuable data for genetic evaluation. In this review, issues related to genetic evaluation of claw health are examined, data sources, trait definitions and data validation p...

  8. Exercise training reverses skeletal muscle atrophy in an experimental model of VCP disease.

    Directory of Open Access Journals (Sweden)

    Angèle Nalbandian

    Full Text Available The therapeutic effects of exercise resistance and endurance training in the alleviation of muscle hypertrophy/atrophy should be considered in the management of patients with advanced neuromuscular diseases. Patients with progressive neuromuscular diseases often experience muscle weakness, which negatively impact independence and quality of life levels. Mutations in the valosin containing protein (VCP gene lead to Inclusion body myopathy associated with Paget's disease of bone and frontotemporal dementia (IBMPFD and more recently affect 2% of amyotrophic lateral sclerosis (ALS-diagnosed cases.The present investigation was undertaken to examine the effects of uphill and downhill exercise training on muscle histopathology and the autophagy cascade in an experimental VCP mouse model carrying the R155H mutation. Progressive uphill exercise in VCP(R155H/+ mice revealed significant improvement in muscle strength and performance by grip strength and Rotarod analyses when compared to the sedentary mice. In contrast, mice exercised to run downhill did not show any significant improvement. Histologically, the uphill exercised VCP(R155H/+ mice displayed an improvement in muscle atrophy, and decreased expression levels of ubiquitin, P62/SQSTM1, LC3I/II, and TDP-43 autophagy markers, suggesting an alleviation of disease-induced myopathy phenotypes. There was also an improvement in the Paget-like phenotype.Collectively, our data highlights that uphill exercise training in VCP(R155H/+ mice did not have any detrimental value to the function of muscle, and may offer effective therapeutic options for patients with VCP-associated diseases.

  9. Serum miRNAs miR-23a, 206, and 499 as Potential Biomarkers for Skeletal Muscle Atrophy

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    Fei Wang

    2017-01-01

    Full Text Available Muscle biopsy has long been expected to be replaced by noninvasive biomarkers with diagnostic value and prognostic applications for muscle atrophy. Growing evidence suggests that circulating microRNAs (miRNAs could act as biomarkers for numerous pathophysiological statuses. In the present study, our results showed that the serum levels of six muscle-specific miRNAs (miR-1/23a/133/206/208b/499 were all elevated in unloading induced mice. The medium levels of these six muscle-specific miRNAs were all elevated in starvation induced atrophic C2C12 myotubes. Moreover, the serum levels of miR-23a/206/499 were induced in participants after 45 days of head-down bed rest (HDBR. The levels of miR-23a/206/499 were positively correlated with the ratio of soleus volume loss in HDBR participants, indicating that they might represent the process of muscle loss. In conclusion, our results demonstrated that circulating miRNAs could serve as useful biochemical and molecular indicators for muscle atrophy diagnosis and disease progression.

  10. Myositis, Ganglioneuritis, and Myocarditis with Distinct Perifascicular Muscle Atrophy in a 2-Year-Old Male Boxer

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    Paul M. Rossman

    2018-02-01

    Full Text Available A 2-year-old male, intact Boxer was referred for chronic diarrhea, hyporexia, labored breathing, weakness and elevated creatine kinase, and alanine aminotransferase activities. Initial examination and diagnostics revealed a peripheral nervous system neurolocalization, atrial premature complexes, and generalized megaesophagus. Progressive worsening of the dog’s condition was noted after 36 h; the dog developed aspiration pneumonia, was febrile and oxygen dependent. The owners elected humane euthanasia. Immediately postmortem biopsies of the left cranial tibial and triceps muscles and the left peroneal nerve were obtained. Postmortem histology revealed concurrent myositis, myocarditis, endocarditis, and ganglioneuritis. Mixed mononuclear cell infiltrations and a distinct perifascicular pattern of muscle fiber atrophy was present in both muscles. This is a novel case of diffuse inflammatory myopathy with a distinct perifascicular pattern of atrophy in addition to endocarditis, myocarditis, and epicarditis.

  11. Myopathic EMG findings and type II muscle fiber atrophy in patients with Lambert-Eaton myasthenic syndrome

    DEFF Research Database (Denmark)

    Crone, Clarissa; Christiansen, Ingelise; Vissing, John

    2013-01-01

    Lambert-Eaton myasthenic syndrome (LEMS) is a rare condition, which may mimic myopathy. A few reports have described that EMG in LEMS may show changes compatible with myopathy, and muscle biopsies have been described with type II as well as type I atrophy. The EMG results were, however, based on ...... on qualitative EMG examination and the histopathological methods were not always clear. The objective of this study was to investigate if the previous EMG findings could be confirmed with quantitative EMG (QEMG) and to describe muscle histology in LEMS.......Lambert-Eaton myasthenic syndrome (LEMS) is a rare condition, which may mimic myopathy. A few reports have described that EMG in LEMS may show changes compatible with myopathy, and muscle biopsies have been described with type II as well as type I atrophy. The EMG results were, however, based...

  12. Aging is associated with diminished muscle re-growth and myogenic precursor cell expansion in the early recovery phase after immobility-induced atrophy in human skeletal muscle

    DEFF Research Database (Denmark)

    Suetta, Charlotte Arneboe; Frandsen, Ulrik; Mackey, Abigail L

    2013-01-01

    Recovery of skeletal muscle mass from immobilisation-induced atrophy is faster in young than older individuals, yet the cellular mechanisms remain unknown. We examined the cellular and molecular regulation of muscle recovery in young and old human subjects subsequent to 2 weeks of immobility...... expression analysis of key growth and transcription factors associated with local skeletal muscle milieu were performed after 2 weeks immobility (Imm) and following 3 days (+3d) and 4 weeks (+4wks) of re-training. OM demonstrated no detectable gains in MFA (VL muscle) and no increases in number of Pax7......-induced muscle atrophy. Re-training consisted of 4 weeks of supervised resistive exercise in 9 older (OM: 67.3yrs, range 61-74) and 11 young (YM: 24.4yrs, range 21-30) males. Measures of myofiber area (MFA), Pax7-positive satellite cells (SC) associated with type I and type II muscle fibres, as well as gene...

  13. Short-term, daily exposure to cold temperature may be an efficient way to prevent muscle atrophy and bone loss in a microgravity environment

    Science.gov (United States)

    Deng, Claudia; Wang, Ping; Zhang, Xiangming; Wang, Ya

    2015-04-01

    Microgravity induces less pressure on muscle/bone, which is a major reason for muscle atrophy as well as bone loss. Currently, physical exercise is the only countermeasure used consistently in the U.S. human space program to counteract the microgravity-induced skeletal muscle atrophy and bone loss. However, the routinely almost daily time commitment is significant and represents a potential risk to the accomplishment of other mission operational tasks. Therefore, development of more efficient exercise programs (with less time) to prevent astronauts from muscle atrophy and bone loss are needed. Consider the two types of muscle contraction: exercising forces muscle contraction and prevents microgravity-induced muscle atrophy/bone loss, which is a voluntary response through the motor nervous system; and cold temperature exposure-induced muscle contraction is an involuntary response through the vegetative nervous system, we formed a new hypothesis. The main purpose of this pilot study was to test our hypothesis that exercise at 4 °C is more efficient than at room temperature to prevent microgravity-induced muscle atrophy/bone loss and, consequently reduces physical exercise time. Twenty mice were divided into two groups with or without daily short-term (10 min × 2, at 12 h interval) cold temperature (4 °C) exposure for 30 days. The whole bodyweight, muscle strength and bone density were measured after terminating the experiments. The results from the one-month pilot study support our hypothesis and suggest that it would be reasonable to use more mice, in a microgravity environment and observe for a longer period to obtain a conclusion. We believe that the results from such a study will help to develop efficient exercise, which will finally benefit astronauts' heath and NASA's missions.

  14. Therapeutic potential of eccentric exercises for age-related muscle atrophy

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    Jae-Young Lim

    2016-09-01

    Full Text Available Recent studies have focused on evidence-based interventions to prevent mobility decline and enhance physical performance in older adults. Several modalities, in addition to traditional strengthening programs, have been designed to manage age-related functional decline more effectively. In this study, we reviewed the current relevant literatures to assess the therapeutic potential of eccentric exercises for age-related muscle atrophy (sarcopenia. Age-related changes in human skeletal muscle, and their relationship with physical performance, are discussed with reference to in vitro physiologic and human biomechanics studies. An overview of issues relevant to sarcopenia is provided in the context of the recent consensus on the diagnosis and management of the condition. A decline in mobility among the aging population is closely linked with changes in the muscle force–velocity relationship. Interventions based specifically on increasing velocity and eccentric strength can improve function more effectively compared with traditional strengthening programs. Eccentric strengthening programs are introduced as a specific method for improving both muscle force and velocity. To be more effective, exercise interventions for older adults should focus on enhancing the muscle force–velocity relationship. Exercises that can be performed easily, and that utilize eccentric strength (which is relatively spared during the aging process, are needed to improve both muscle force and velocity.

  15. Comparison of MRI and DXA to measure muscle size and age-related atrophy in thigh muscles.

    Science.gov (United States)

    Maden-Wilkinson, T M; Degens, H; Jones, D A; McPhee, J S

    2013-09-01

    Magnetic resonance imaging (MRI) and dual-energy x-ray absorptiometry (DXA) were used to examine the thigh lean mass in young and old men and women. A whole-body DXA scan was used to estimate thigh lean mass in young (20 men; 22.4±3.1y; 18 women; 22.1±2.0y) and older adults (25 men; 72.3±4.9y; 28 women; 72.0±4.5y). Thigh lean mass determined with a thigh scan on the DXA or full thigh MRI scans were compared. Although the thigh lean mass quantified by DXA and MRI in young and older participants were correlated (R(2)=0.88; polder than young individuals, while the other thigh muscles were only 18% smaller. DXA underestimates the age-related loss of thigh muscle mass in comparison to MRI. The quadriceps muscles were more susceptible to age-related atrophy compared with other thigh muscles.

  16. Multifidus Muscle Changes After Back Injury Are Characterized by Structural Remodeling of Muscle, Adipose and Connective Tissue, but Not Muscle Atrophy: Molecular and Morphological Evidence.

    Science.gov (United States)

    Hodges, Paul W; James, Gregory; Blomster, Linda; Hall, Leanne; Schmid, Annina; Shu, Cindy; Little, Chris; Melrose, James

    2015-07-15

    Longitudinal case-controlled animal study. To investigate putative cellular mechanisms to explain structural changes in muscle and adipose and connective tissues of the back muscles after intervertebral disc (IVD) injury. Structural back muscle changes are ubiquitous with back pain/injury and considered relevant for outcome, but their exact nature, time course, and cellular mechanisms remain elusive. We used an animal model that produces phenotypic back muscle changes after IVD injury to study these issues at the cellular/molecular level. Multifidus muscle was harvested from both sides of the spine at L1-L2 and L3-L4 IVDs in 27 castrated male sheep at 3 (n = 10) or 6 (n = 17) months after a surgical anterolateral IVD injury at both levels. Ten control sheep underwent no surgery (3 mo, n = 4; 6 mo, n = 6). Tissue was harvested at L4 for histological analysis of cross-sectional area of muscle and adipose and connective tissue (whole muscle), plus immunohistochemistry to identify proportion and cross-sectional area of individual muscle fiber types in the deepest fascicle. Quantitative polymerase chain reaction measured gene expression of typical cytokines/signaling molecules at L2. Contrary to predictions, there was no multifidus muscle atrophy (whole muscle or individual fiber). There was increased adipose and connective tissue (fibrotic proliferation) cross-sectional area and slow-to-fast muscle fiber transition at 6 but not 3 months. Within the multifidus muscle, increases in the expression of several cytokines (tumor necrosis factor α and interleukin-1β) and molecules that signal trophic/atrophic processes for the 3 tissue types (e.g., growth factor pathway [IGF-1, PI3k, Akt1, mTOR], potent tissue modifiers [calcineurin, PCG-1α, and myostatin]) were present. This study provides cellular evidence that refutes the presence of multifidus muscle atrophy accompanying IVD degeneration at this intermediate time point. Instead, adipose/connective tissue increased in

  17. The use of muscle biopsy in the diagnosis of undefined ataxia with cerebellar atrophy in children.

    Science.gov (United States)

    Terracciano, Alessandra; Renaldo, Florence; Zanni, Ginevra; D'Amico, Adele; Pastore, Anna; Barresi, Sabina; Valente, Enza Maria; Piemonte, Fiorella; Tozzi, Giulia; Carrozzo, Rosalba; Valeriani, Massimiliano; Boldrini, Renata; Mercuri, Eugenio; Santorelli, Filippo Maria; Bertini, Enrico

    2012-05-01

    Childhood cerebellar ataxias, and particularly congenital ataxias, are heterogeneous disorders and several remain undefined. We performed a muscle biopsy in patients with congenital ataxia and children with later onset undefined ataxia having neuroimaging evidence of cerebellar atrophy. Significant reduced levels of Coenzyme Q10 (COQ10) were found in the skeletal muscle of 9 out of 34 patients that were consecutively screened. A mutation in the ADCK3/Coq8 gene (R347X) was identified in a female patient with ataxia, seizures and markedly reduced COQ10 levels. In a 2.5-years-old male patient with non syndromic congenital ataxia and autophagic vacuoles in the muscle biopsy we identified a homozygous nonsense mutation R111X mutation in SIL1 gene, leading to early diagnosis of Marinesco-Sjogren syndrome. We think that muscle biopsy is a valuable procedure to improve diagnostic assesement in children with congenital ataxia or other undefined forms of later onset childhood ataxia associated to cerebellar atrophy at MRI. Copyright © 2011 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  18. Beneficial effects of GH/IGF-1 on skeletal muscle atrophy and function in experimental heart failure.

    Science.gov (United States)

    Dalla Libera, Luciano; Ravara, Barbara; Volterrani, Maurizio; Gobbo, Valerio; Della Barbera, Mila; Angelini, Annalisa; Danieli Betto, Daniela; Germinario, Elena; Vescovo, Giorgio

    2004-01-01

    Muscle atrophy is a determinant of exercise capacity in heart failure (CHF). Myocyte apoptosis, triggered by tumor necrosis factor-alpha (TNF-alpha) or its second messenger sphingosine (SPH), is one of the causes of atrophy. Growth hormone (GH) improves hemodynamic and cardiac trophism in several experimental models of CHF, but its effect on skeletal muscle in CHF is not yet clear. We tested the hypothesis that GH can prevent skeletal muscle apoptosis in rats with CHF. CHF was induced by injecting monocrotaline. After 2 wk, 2 groups of rats were treated with GH (0.2 mg.kg(-1).day(-1) and 1.0 mg.kg(-1).day(-1)) subcutaneously. A third group of controls had saline. After 2 additional weeks, rats were killed. Tibialis anterior cross-sectional area, myosin heavy chain (MHC) composition, and a study on myocyte apoptosis and serum levels of TNF-alpha and SPH were carried out. The number of apoptotic nuclei, muscle atrophy, and serum levels of TNF-alpha and SPH were decreased with GH at high but not at low doses compared with CHF rats. Bcl-2 was increased, whereas activated caspases and bax were decreased. The MHC pattern in GH-treated animals was similar to that of controls. Monocrotaline slowed down both contraction and relaxation but did not affect specific tetanic force, whereas absolute force was decreased. GH treatment restored contraction and relaxation to control values and brought muscle mass and absolute twitch and tetanic tension to normal levels. These findings may provide an insight into the therapeutic strategy of GH given to patients with CHF to improve exercise capacity.

  19. Association of claw disorders with claw horn colour in norwegian red cattle - a cross-sectional study of 2607 cows from 112 herds

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    Sogstad Åse M

    2011-11-01

    Full Text Available Abstract Claw disorders cause problems in dairy cattle all over the world. Nutrition, feeding, environment, claw trimming routines, hormonal changes related to calving and genetics are among the factors which influence the pathogenesis. The colour of the claw horn (pigmentation has been suggested to play a role. The aim of this study was to investigate if there were any associations between the colour of the sole horn and claw disorders detected at claw trimming. Altogether, 2607 cows on 112 farms were claw trimmed once and the colour (dark, mixed or light of the right lateral hind claw and hind claw disorders were recorded by 13 trained claw trimmers. The data were analysed using logistic regression models with logit link function, binomial distribution and herd and claw trimmer as repeated effects, with herd nested within claw trimmer. Haemorrhages of the sole (HS and white line (HWL were more frequently found in light than in dark claws (OR = 2.61 and 2.34, respectively. Both HS (OR = 1.43 and corkscrewed claws (OR = 1.84 were slightly more prevalent among cows which had claws with mixed colour versus dark claws. There were no significant associations of other claw disorders with claw horn colour.

  20. Effect of Electroacupuncture on the Expression of Glycyl-tRNA Synthetase and Ultrastructure Changes in Atrophied Rat Peroneus Longus Muscle Induced by Sciatic Nerve Injection Injury

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    Meng Wang

    2016-01-01

    Full Text Available Glycyl-tRNA synthetase (GlyRS is one of the key enzymes involved in protein synthesis. Its mutations have been reported to cause Charcot-Marie-Tooth disease which demonstrates muscular atrophy in distal extremities, particularly manifested in peroneus muscles. In this situation, the dysfunctions of mitochondria and sarcoplasmic reticulum (SR affect energy supply and excitation-contraction coupling of muscle fibers, therefore resulting in muscular atrophy. Although the treatment of muscular atrophy is a global urgent problem, it can be improved by electroacupuncture (EA treatment. To investigate the mechanism underlying EA treatment improving muscular atrophy, we focused on the perspective of protein synthesis by establishing a penicillin injection-induced sciatic nerve injury model. In our model, injured rats without treatment showed decreased sciatic functional index (SFI, decreased peroneus longus muscle weight and muscle fiber cross-sectional area, aggregated mitochondria with vacuoles appearing, swollen SR, and downregulated mRNA and protein expression levels of GlyRS and myosin heavy chain IIb (MHC-IIb. The injured rats with EA treatment showed significant recovery. These results indicated that EA stimulation can alleviate peroneus longus muscular atrophy induced by iatrogenic sciatic nerve injury through promoting the recovery of GlyRS and muscle ultrastructure and increasing muscle protein synthesis.

  1. Early Detection of Atrophy of Foot Muscles in Chinese Patients of Type 2 Diabetes Mellitus by High-Frequency Ultrasonography

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    Xiaohui Wang

    2014-01-01

    Full Text Available The aim of this study was to evaluate the diagnostic value of high-frequency ultrasonography in detecting atrophy of foot muscles in Chinese patients of type 2 diabetes mellitus (T2DM. Chinese patients of T2DM with (n=56 or without (n=50 diabetic peripheral neuropathy (DPN and the control subjects (n=50 were enrolled. The nondominant foot of all subjects was examined with high-frequency ultrasonography. The transverse diameter, thickness, and cross-sectional area of the extensor digitorum brevis muscle (EDB and the thickness of the muscles of the first interstitium (MILs were measured. The results showed that the ultrasonographic transverse diameter, thickness, and cross-sectional area of EDB and the thickness of MILs in patients of T2DM with DPN were significantly smaller than those in patients of T2DM without DPN (all P<0.01 and those in the control subjects (all P<0.01. The transverse diameter and cross-sectional area of the EDB and thickness of MILs in patients of T2DM without DPN were significantly smaller than those of the control subjects (all P<0.01. In conclusion, the atrophy of foot muscle in Chinese T2DM patients can be detected by high-frequency ultrasonography. Notably, ultrasonography may detect early atrophy of foot muscles in patients without DPN.

  2. Exposure to microgravity for 30 days onboard Bion M1 caused muscle atrophy and impaired regeneration in murine femoral Quadriceps

    Science.gov (United States)

    Radugina, E. A.; Almeida, E. A. C.; Blaber, E.; Poplinskaya, V. A.; Markitantova, Y. V.; Grigoryan, E. N.

    2018-02-01

    Mechanical unloading in microgravity during spaceflight is known to cause muscular atrophy, changes in muscle fiber composition, gene expression, and reduction in regenerative muscle growth. Although some limited data exists for long-term effects of microgravity in human muscle, these processes have mostly been studied in rodents for short periods of time. Here we report on how long-term (30-day long) mechanical unloading in microgravity affects murine muscles of the femoral Quadriceps group. To conduct these studies we used muscle tissue from 6 microgravity mice, in comparison to habitat (7), and vivarium (14) ground control mice from the NASA Biospecimen Sharing Program conducted in collaboration with the Institute for Biomedical Problems of the Russian Academy of Sciences, during the Russian Bion M1 biosatellite mission in 2013. Muscle histomorphology from microgravity specimens showed signs of extensive atrophy and regenerative hypoplasia relative to ground controls. Specifically, we observed a two-fold decrease in the number of myonuclei, compared to vivarium and ground controls, and central location of myonuclei, low density of myofibers in the tissue, and of myofibrils within a fiber, as well as fragmentation and swelling of myofibers. Despite obvious atrophy, muscle regeneration nevertheless appeared to have continued after 30 days in microgravity as evidenced by thin and short newly formed myofibers. Many of them, however, showed evidence of apoptotic cells and myofibril degradation, suggesting that long-term unloading in microgravity may affect late stages of myofiber differentiation. Ground asynchronous and vivarium control animals demonstrated normal, well-developed tissue structure with sufficient blood and nerve supply and evidence of regenerative formation of new myofibers free of apoptotic nuclei. Regenerative activity of satellite cells in muscles was observed both in microgravity and ground control groups, using Pax7 and Myogenin

  3. Clubbed fingers: the claws we lost?

    NARCIS (Netherlands)

    Brouwers, A.A.M.; Vermeij-Keers, C.; Zoelen, E.J.J. van; Gooren, L.J.G.

    2004-01-01

    Clubbed digits resemble the human embryonic fingers and toes, which took like the digits of a claw. Clubbed digits, thus, may represent the return of the embryonic claw and may even represent the claws man has lost during evolution, if ontogenesis realty recapitulates phylogenesis. We put forward

  4. Measurement of a MMP-2 degraded Titin fragment in serum reflects changes in muscle turnover induced by atrophy.

    Science.gov (United States)

    Sun, S; Henriksen, K; Karsdal, M A; Armbrecht, G; Belavý, D L; Felsenberg, D; Rittweger, J; Wang, Y; Zheng, Q; Nedergaard, A F

    2014-10-01

    In this study we sought to determine whether a Titin peptide fragment can serve as a clinical biomarker for changes in muscle mass. Mass spectrometry was used to identify Titin fragment in urine. An antibody against this Titin sequence was raised and used to develop a competitive ELISA assay for measurement in serum. Rat tissue extractions in the presence or absence of a series of proteases of interest were used to identify its enzymatic origin. A rat model of dexamethasone (DEX) induced muscle atrophy and a human 56-day bed rest study with and without vibration therapy were used to assess biological and clinical relevance. A technically robust ELISA measuring the Titin fragment was developed against a Titin peptide fragment identified in human urine. The fragment was shown to be produced primarily by MMP-2 cleavage of Titin. In the rat muscle DEX induced atrophy model, Titin-MMP2 fragment was decreased in the beginning of DEX treatment, and then significantly increased later on during DEX administration. In the human bed rest study, the Titin-MMP2 fragment was initially decreased 11.9 (±3.7) % after 1day of bed rest, and then gradually increased ending up at a 16.4 (±4.6) % increase at day 47. We developed a robust ELISA measuring a muscle derived MMP-2 generated Titin degradation fragment in rat and human serum. Importantly, the fragment can be measured in serum and that these levels are related to induction of skeletal muscle atrophy. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Short-term muscle atrophy caused by botulinum toxin-A local injection impairs fracture healing in the rat femur.

    Science.gov (United States)

    Hao, Yongqiang; Ma, Yongcheng; Wang, Xuepeng; Jin, Fangchun; Ge, Shengfang

    2012-04-01

    Damaged bone is sensitive to mechanical stimulation throughout the remodeling phase of bone healing. Muscle damage and muscular atrophy associated with open fractures and subsequent fixation are not beneficial to maintaining optimum conditions for mechanical stability. The aim of this study was to investigate whether local muscle atrophy and dysfunction affect fracture healing in a rat femur fracture model. We combined the rat model of a short period atrophy of the quadriceps with femur fracture. Forty-four-month-old male Wistar rats were adopted for this study. Two units of botulinum toxin-A (BXTA) were administered locally into the right side of the quadriceps of each rat, while the same dose of saline was injected into the contralateral quadriceps. After BXTA had been fully absorbed by the quadriceps, osteotomy was performed in both femurs with intramedullary fixation. Gross observation and weighing of muscle tissue, X-ray analysis, callus histology, and bone biomechanical testing were performed at different time points up to 8 weeks post-surgery. Local injection of BXTA led to a significant decrease in the volume and weight of the quadriceps compared to the control side. At the eighth week, the left side femurs of the saline-injected quadriceps almost reached bony union, and fibrous calluses were completely calcified into woven bone. However, a gap was still visible in the BXTA-treated side on X-ray images. As showed by bone histology, there were no mature osseous calluses or woven bone on the BXTA-treated side, but a resorption pattern was evident. Biomechanical testing indicated that the femurs of the BXTA-treated side exhibited inferior mechanical properties compared with the control side. The inferior outcome following BXTA injection, compared with saline injection, in terms of callus resistance may be the consequence of unexpected load and mechanical unsteadiness caused by muscle atrophy and dysfunction. Copyright © 2011 Orthopaedic Research Society.

  6. Serum Amyloid A Induces Toll-Like Receptor 2-Dependent Inflammatory Cytokine Expression and Atrophy in C2C12 Skeletal Muscle Myotubes.

    Science.gov (United States)

    Passey, Samantha L; Bozinovski, Steven; Vlahos, Ross; Anderson, Gary P; Hansen, Michelle J

    2016-01-01

    Skeletal muscle wasting is an important comorbidity of Chronic Obstructive Pulmonary Disease (COPD) and is strongly correlated with morbidity and mortality. Patients who experience frequent acute exacerbations of COPD (AECOPD) have more severe muscle wasting and reduced recovery of muscle mass and function after each exacerbation. Serum levels of the pro-inflammatory acute phase protein Serum Amyloid A (SAA) can rise more than 1000-fold in AECOPD and are predictively correlated with exacerbation severity. The direct effects of SAA on skeletal muscle are poorly understood. Here we have examined SAA effects on pro-inflammatory cachectic cytokine expression (IL-6 and TNFα) and atrophy in C2C12 myotubes. SAA increased IL-6 (31-fold) and TNFα (6.5-fold) mRNA levels compared to control untreated cells after 3h of SAA treatment, and increased secreted IL-6 protein at 24h. OxPAPC, a dual TLR2 and TLR4 inhibitor, reduced the response to SAA by approximately 84% compared to SAA alone, and the TLR2 neutralising antibody T2.5 abolished SAA-induced expression of IL-6, indicating that SAA signalling in C2C12 myotubes is primarily via TLR2. SAA also reduced myotube width by 10-13% and induced a 2.5-fold increase in the expression of the muscle atrophy gene Atrogin-1, suggesting direct effects of SAA on muscle wasting. Blocking of TLR2 inhibited the SAA-induced decrease in myotube width and Atrogin-1 gene expression, indicating that SAA induces atrophy through TLR2. These data demonstrate that SAA stimulates a robust pro-inflammatory response in skeletal muscle myotubes via the TLR2-dependent release of IL-6 and TNFα. Furthermore, the observed atrophy effects indicate that SAA could also be directly contributing to the wasting and poor recovery of muscle mass. Therapeutic strategies targeting this SAA-TLR2 axis may therefore ameliorate muscle wasting in AECOPD and a range of other inflammatory conditions associated with loss of muscle mass.

  7. Inhibition of Stat3 signaling ameliorates atrophy of the soleus muscles in mice lacking the vitamin D receptor.

    Science.gov (United States)

    Gopinath, Suchitra D

    2017-01-25

    Although skeletal muscle wasting has long been observed as a clinical outcome of impaired vitamin D signaling, precise molecular mechanisms that mediate the loss of muscle mass in the absence of vitamin D signaling are less clear. To determine the molecular consequences of vitamin D signaling, we analyzed the role of signal transducer and activator of transcription 3 (Stat3) signaling, a known contributor to various muscle wasting pathologies, in skeletal muscles. We isolated soleus (slow) and tibialis anterior (fast) muscles from mice lacking the vitamin D receptor (VDR -/- ) and used western blot analysis, quantitative RTPCR, and pharmacological intervention to analyze muscle atrophy in VDR -/- mice. We found that slow and fast subsets of muscles of the VDR -/- mice displayed elevated levels of phosphorylated Stat3 accompanied by an increase in Myostatin expression and signaling. Consequently, we observed reduced activity of mammalian target of rapamycin (mTOR) signaling components, ribosomal S6 kinase (p70S6K) and ribosomal S6 protein (rpS6), that regulate protein synthesis and cell size, respectively. Concomitantly, we observed an increase in atrophy regulators and a block in autophagic gene expression. An examination of the upstream regulation of Stat3 levels in VDR -/- muscles revealed an increase in IL-6 protein expression in the soleus, but not in the tibialis anterior muscles. To investigate the involvement of satellite cells (SCs) in atrophy in VDR -/- mice, we found that there was no significant deficit in SC numbers in VDR -/- muscles compared to the wild type. Unlike its expression within VDR -/- fibers, Myostatin levels in VDR -/- SCs from bulk muscles were similar to those of wild type. However, VDR -/- SCs induced to differentiate in culture displayed increased p-Stat3 signaling and Myostatin expression. Finally, VDR -/- mice injected with a Stat3 inhibitor displayed reduced Myostatin expression and function and restored active p70S6K and rpS6

  8. Reply to: Can we avoid rectus abdominis muscle atrophy and midline shift after colostomy creation?

    NARCIS (Netherlands)

    L. Timmermans (Lucas); E.B. Deerenberg (Eva); S.M. van Dijk (Sven); B. Lamme (Bas); A.H.J. Koning (Anton); G.J. Kleinrensink (Gert Jan); J. Jeekel (Johannes); J.F. Lange (Johan)

    2015-01-01

    markdownabstractWe read with interest the letter to the editor by Stephenson et al regarding our article “Abdominal rectus muscle atrophy and midline shift after colostomy creation.” Any attempt to decrease the risk of parastomal herniation should be applauded, because its incidence of greater than

  9. Atrophy of Swallowing Muscles Is Associated With Severity of Dysphagia and Age in Patients With Acute Stroke.

    Science.gov (United States)

    Sporns, Peter B; Muhle, Paul; Hanning, Uta; Suntrup-Krueger, Sonja; Schwindt, Wolfram; Eversmann, Julian; Warnecke, Tobias; Wirth, Rainer; Zimmer, Sebastian; Dziewas, Rainer

    2017-07-01

    Sarcopenia has been identified as an independent risk factor for dysphagia. Dysphagia is one of the most important and prognostically relevant complications of acute stroke. The role of muscle atrophy as a contributing factor for the occurrence of poststroke dysphagia is yet unclear. To assess whether there is a correlation between age and muscle volume and whether muscle volume is related to dysphagia in acute stroke patients. This retrospective, single-center study included 73 patients with acute ischemic or hemorrhagic stroke who underwent computed tomography angiography on admission and an objective dysphagia assessment by Fiberoptic Endoscopic Evaluation of Swallowing within 72 hours from admission. With the help of semiautomated muscle segmentation and 3-dimensional reconstruction volumetry of the digastric, temporal, and geniohyoid muscles was performed. For further analysis, participants were first divided into 4 groups according to their age (dysphagia severity using the Fiberoptic Endoscopic Dysphagia Severity Scale (FEDSS) (FEDSS 1 and 2, n = 25; FEDSS 3 and 4, n = 32; FEDSS 5 and 6, n = 16). Correlation of muscle volumes with age and dysphagia severity. Muscle volumes of single muscles (except for geniohyoid and the right digastric muscles) as well as the sum muscle volume were significantly and inversely related to dysphagia severity. We found a significant decline of muscle volume with advancing age for most muscle groups and, in particular, for the total muscle volume. Apart from features being determined by the acute stroke itself (eg, site and size of stroke), also premorbid conditions, in particular age-related muscle atrophy, have an impact on the complex pathophysiology of swallowing disorders poststroke. Copyright © 2017 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

  10. Agrin mutations lead to a congenital myasthenic syndrome with distal muscle weakness and atrophy.

    Science.gov (United States)

    Nicole, Sophie; Chaouch, Amina; Torbergsen, Torberg; Bauché, Stéphanie; de Bruyckere, Elodie; Fontenille, Marie-Joséphine; Horn, Morten A; van Ghelue, Marijke; Løseth, Sissel; Issop, Yasmin; Cox, Daniel; Müller, Juliane S; Evangelista, Teresinha; Stålberg, Erik; Ioos, Christine; Barois, Annie; Brochier, Guy; Sternberg, Damien; Fournier, Emmanuel; Hantaï, Daniel; Abicht, Angela; Dusl, Marina; Laval, Steven H; Griffin, Helen; Eymard, Bruno; Lochmüller, Hanns

    2014-09-01

    Congenital myasthenic syndromes are a clinically and genetically heterogeneous group of rare diseases resulting from impaired neuromuscular transmission. Their clinical hallmark is fatigable muscle weakness associated with a decremental muscle response to repetitive nerve stimulation and frequently related to postsynaptic defects. Distal myopathies form another clinically and genetically heterogeneous group of primary muscle disorders where weakness and atrophy are restricted to distal muscles, at least initially. In both congenital myasthenic syndromes and distal myopathies, a significant number of patients remain genetically undiagnosed. Here, we report five patients from three unrelated families with a strikingly homogenous clinical entity combining congenital myasthenia with distal muscle weakness and atrophy reminiscent of a distal myopathy. MRI and neurophysiological studies were compatible with mild myopathy restricted to distal limb muscles, but decrement (up to 72%) in response to 3 Hz repetitive nerve stimulation pointed towards a neuromuscular transmission defect. Post-exercise increment (up to 285%) was observed in the distal limb muscles in all cases suggesting presynaptic congenital myasthenic syndrome. Immunofluorescence and ultrastructural analyses of muscle end-plate regions showed synaptic remodelling with denervation-reinnervation events. We performed whole-exome sequencing in two kinships and Sanger sequencing in one isolated case and identified five new recessive mutations in the gene encoding agrin. This synaptic proteoglycan with critical function at the neuromuscular junction was previously found mutated in more typical forms of congenital myasthenic syndrome. In our patients, we found two missense mutations residing in the N-terminal agrin domain, which reduced acetylcholine receptors clustering activity of agrin in vitro. Our findings expand the spectrum of congenital myasthenic syndromes due to agrin mutations and show an unexpected

  11. Measurement of a MMP-2 degraded Titin fragment in serum reflects changes in muscle turnover induced by atrophy

    DEFF Research Database (Denmark)

    Sun, S; Henriksen, K; Karsdal, M A

    2014-01-01

    used to assess biological and clinical relevance. RESULTS: A technically robust ELISA measuring the Titin fragment was developed against a Titin peptide fragment identified in human urine. The fragment was shown to be produced primarily by MMP-2 cleavage of Titin. In the rat muscle DEX induced atrophy...... model, Titin-MMP2 fragment was decreased in the beginning of DEX treatment, and then significantly increased later on during DEX administration. In the human bed rest study, the Titin-MMP2 fragment was initially decreased 11.9 (±3.7) % after 1day of bed rest, and then gradually increased ending up...... at a 16.4 (±4.6) % increase at day 47. CONCLUSIONS: We developed a robust ELISA measuring a muscle derived MMP-2 generated Titin degradation fragment in rat and human serum. Importantly, the fragment can be measured in serum and that these levels are related to induction of skeletal muscle atrophy....

  12. Does successful rotator cuff repair improve muscle atrophy and fatty infiltration of the rotator cuff? A retrospective magnetic resonance imaging study performed shortly after surgery as a reference.

    Science.gov (United States)

    Hamano, Noritaka; Yamamoto, Atsushi; Shitara, Hitoshi; Ichinose, Tsuyoshi; Shimoyama, Daisuke; Sasaki, Tsuyoshi; Kobayashi, Tsutomu; Kakuta, Yohei; Osawa, Toshihisa; Takagishi, Kenji

    2017-06-01

    Muscle atrophy and fatty infiltration in the rotator cuff muscles are often observed in patients with chronic rotator cuff tears. The recovery from these conditions has not been clarified. Ninety-four patients were included in this study. The improvement in muscle atrophy and fatty infiltration in successfully repaired rotator cuff tears was evaluated by magnetic resonance imaging at 1 year and 2 years after surgery and was compared with muscle atrophy and fatty infiltration observed on magnetic resonance imaging at 2 weeks after surgery to discount any changes due to the medial retraction of the torn tendon. The patients' muscle strength was evaluated in abduction and external rotation. Muscle atrophy and fatty infiltration of the supraspinatus were significantly improved at 2 years after surgery in comparison to 2 weeks after surgery. The subjects' abduction and external rotation strength was also significantly improved at 2 years after surgery in comparison to the preoperative values. Patients whose occupation ratio was improved had a better abduction range of motion, stronger abduction strength, and higher Constant score. Patients whose fatty infiltration was improved had a better range of motion in flexion and abduction, whereas the improvements of muscle strength and the Constant score were similar in the group that showed an improvement of fatty infiltration and the group that did not. Muscle atrophy and fatty infiltration can improve after rotator cuff repair. The strengths of abduction and external rotation were also improved at 2 years after surgery. Copyright © 2016 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

  13. Unilateral hindlimb casting induced a delayed generalized muscle atrophy during rehabilitation that is prevented by a whey or a high protein diet but not a free leucine-enriched diet.

    Directory of Open Access Journals (Sweden)

    Hugues Magne

    Full Text Available Sarcopenia is the general muscle mass and strength loss associated with ageing. Muscle atrophy could be made worse by exposure to acute periods of immobilization, because muscle disuse by itself is a stimulus for atrophy. Using a model of unilateral hindlimb casting in old adult rats, we have already demonstrated that the primary effect of immobilization was atrophy in the casted leg, but was also surprisingly associated with a retarded atrophy in the non-casted leg during rehabilitation. In search of mechanisms involved in this generalized atrophy, we demonstrated in the present study that contrary to pair-fed non-immobilized control animals, muscle protein synthesis in the non-immobilized limb was unable to adapt and to respond positively to food intake. Because pair-fed control rats did not lose muscle mass, this defect in muscle protein synthesis may represent one of the explanation for the muscle mass loss observed in the non-immobilized rats. Nevertheless, in order to stimulate protein turn over and generate a positive nitrogen balance required to maintain the whole muscle mass in immobilized rats, we tested a dietary free leucine supplementation (an amino acid known for its stimulatory effect on protein metabolism during the rehabilitation period. Leucine supplementation was able to overcome the anabolic resistance in the non-immobilized limb. A greater muscle protein synthesis up-regulation associated with a stimulation of the mTOR signalling pathway was indeed recorded but it remained inefficient to prevent the loss of muscle in the non-immobilized limb. By contrast, we demonstrated here that whey protein or high protein diets were able to prevent the muscle mass loss of the non-immobilized limb by sustaining muscle protein synthesis during the entire rehabilitation period.

  14. Calpain 3 and CaMKIIβ signaling are required to induce HSP70 necessary for adaptive muscle growth after atrophy

    Science.gov (United States)

    Kramerova, Irina; Torres, Jorge A; Eskin, Ascia; Nelson, Stanley F; Spencer, Melissa J

    2018-01-01

    Abstract Mutations in CAPN3 cause autosomal recessive limb girdle muscular dystrophy 2A. Calpain 3 (CAPN3) is a calcium dependent protease residing in the myofibrillar, cytosolic and triad fractions of skeletal muscle. At the triad, it colocalizes with calcium calmodulin kinase IIβ (CaMKIIβ). CAPN3 knock out mice (C3KO) show reduced triad integrity and blunted CaMKIIβ signaling, which correlates with impaired transcriptional activation of myofibrillar and oxidative metabolism genes in response to running exercise. These data suggest a role for CAPN3 and CaMKIIβ in gene regulation that takes place during adaptation to endurance exercise. To assess whether CAPN3- CaMKIIβ signaling influences skeletal muscle remodeling in other contexts, we subjected C3KO and wild type mice to hindlimb unloading and reloading and assessed CaMKIIβ signaling and gene expression by RNA-sequencing. After induced atrophy followed by 4 days of reloading, both CaMKIIβ activation and expression of inflammatory and cellular stress genes were increased. C3KO muscles failed to activate CaMKIIβ signaling, did not activate the same pattern of gene expression and demonstrated impaired growth at 4 days of reloading. Moreover, C3KO muscles failed to activate inducible HSP70, which was previously shown to be indispensible for the inflammatory response needed to promote muscle recovery. Likewise, C3KO showed diminished immune cell infiltration and decreased expression of pro-myogenic genes. These data support a role for CaMKIIβ signaling in induction of HSP70 and promotion of the inflammatory response during muscle growth and remodeling that occurs after atrophy, suggesting that CaMKIIβ regulates remodeling in multiple contexts: endurance exercise and growth after atrophy. PMID:29528394

  15. Muscular atrophy in diabetic neuropathy

    DEFF Research Database (Denmark)

    Andersen, H; Gadeberg, P C; Brock, B

    1997-01-01

    Diabetic patients with polyneuropathy develop motor dysfunction. To establish whether motor dysfunction is associated with muscular atrophy the ankle dorsal and plantar flexors of the non-dominant leg were evaluated with magnetic resonance imaging in 8 patients with symptomatic neuropathy, in 8 non...... confirmed that the atrophy predominated distally. We conclude that muscular atrophy underlies motor weakness at the ankle in diabetic patients with polyneuropathy and that the atrophy is most pronounced in distal muscles of the lower leg indicating that a length dependent neuropathic process explains...

  16. Electrical Stimulation of Denervated Rat Skeletal Muscle Retards Capillary and Muscle Loss in Early Stages of Disuse Atrophy

    Directory of Open Access Journals (Sweden)

    Kouki Nakagawa

    2017-01-01

    Full Text Available The purpose of the present study is to investigate the effects of low-frequency electrical muscle stimulation (ES on the decrease in muscle mass, fiber size, capillary supply, and matrix metalloproteinase (MMP immunoreactivity in the early stages of denervation-induced limb disuse. Direct ES was performed on the tibialis anterior muscle following denervation in seven-week-old male rats. The rats were divided into the following groups: control (CON, denervation (DN, and denervation with direct ES (DN + ES. Direct ES was performed at an intensity of 16 mA and a frequency of 10 Hz for 30 min per day, six days a week, for one week. We performed immunohistochemical staining to determine the expression of dystrophin, CD34, and MMP-2 in transverse sections of TA muscles. The weight, myofiber cross-sectional area (FCSA, and capillary-to-fiber (C/F ratio of the tibialis anterior (TA muscle were significantly reduced in the DN group compared to the control and DN + ES groups. The MMP-2 positive area was significantly greater in DN and DN + ES groups compared to the control group. These findings suggest beneficial effects of direct ES in reducing muscle atrophy and capillary regression without increasing MMP-2 immunoreactivity in the early stages of DN-induced muscle disuse in rat hind limbs.

  17. Electrical Stimulation of Denervated Rat Skeletal Muscle Retards Capillary and Muscle Loss in Early Stages of Disuse Atrophy

    Science.gov (United States)

    Nakagawa, Kouki; Hayao, Keishi; Yotani, Kengo; Ogita, Futoshi; Yamamoto, Noriaki; Onishi, Hideaki

    2017-01-01

    The purpose of the present study is to investigate the effects of low-frequency electrical muscle stimulation (ES) on the decrease in muscle mass, fiber size, capillary supply, and matrix metalloproteinase (MMP) immunoreactivity in the early stages of denervation-induced limb disuse. Direct ES was performed on the tibialis anterior muscle following denervation in seven-week-old male rats. The rats were divided into the following groups: control (CON), denervation (DN), and denervation with direct ES (DN + ES). Direct ES was performed at an intensity of 16 mA and a frequency of 10 Hz for 30 min per day, six days a week, for one week. We performed immunohistochemical staining to determine the expression of dystrophin, CD34, and MMP-2 in transverse sections of TA muscles. The weight, myofiber cross-sectional area (FCSA), and capillary-to-fiber (C/F) ratio of the tibialis anterior (TA) muscle were significantly reduced in the DN group compared to the control and DN + ES groups. The MMP-2 positive area was significantly greater in DN and DN + ES groups compared to the control group. These findings suggest beneficial effects of direct ES in reducing muscle atrophy and capillary regression without increasing MMP-2 immunoreactivity in the early stages of DN-induced muscle disuse in rat hind limbs. PMID:28497057

  18. Muscle atrophy as pre-sarcopenia in Japanese patients with chronic liver disease: computed tomography is useful for evaluation

    OpenAIRE

    Hiraoka, Atsushi; Aibiki, Toshihiko; Okudaira, Tomonari; Toshimori, Akiko; Kawamura, Tomoe; Nakahara, Hiromasa; Suga, Yoshifumi; Azemoto, Nobuaki; Miyata, Hideki; Miyamoto, Yasunao; Ninomiya, Tomoyuki; Hirooka, Masashi; Abe, Masanori; Matsuura, Bunzo; Hiasa, Yoichi

    2015-01-01

    Background/Aim The definition of muscle atrophy (pre-sarcopenia) and its diagnostic criteria have not been well reported. To elucidate the frequency of pre-sarcopenia in chronic liver disease (CLD), we examined clinical features of Japanese CLD patients using abdominal computed tomography (CT) findings. Methods We enrolled 988 CLD (736 with na?ve hepatocellular carcinoma) and 372 normal control subjects (NCs). The psoas muscle area index [PI, psoas muscle area at the mid-L3 level in CT (cm2)/...

  19. Development, comparative morphology and cornification of reptilian claws in relation to claws evolution in tetrapods

    NARCIS (Netherlands)

    Alibardi, L.

    2009-01-01

    The development of claws in different reptiles and their cornification are analyzed using histological, ultrastructural and autoradiographic methods. Claws develop at the tip of digits in relation to the growth of the terminal phalanx and appear as modified scales. The apical epidermis of digit

  20. Insulin signaling and skeletal muscle atrophy and autophagy in transition dairy cows either overfed energy or fed a controlled energy diet prepartum.

    Science.gov (United States)

    Mann, S; Abuelo, A; Nydam, D V; Leal Yepes, F A; Overton, T R; Wakshlag, J J

    2016-05-01

    During periods of negative energy balance, mobilization of muscle is a physiologic process providing energy and amino acids. This is important in transition dairy cows experiencing negative energy and protein balance postpartum. Overconsumption of energy during late pregnancy affects resting glucose and insulin concentrations peripartum and increases the risk for hyperketonemia postpartum, but the effects on muscle tissue are not fully understood. Skeletal muscle accounts for the majority of insulin-dependent glucose utilization in ruminants. Our objective was to study peripartal skeletal muscle insulin signaling as well as muscle accretion and atrophy in cows with excess energy consumption prepartum. Skeletal muscle biopsies were obtained 28 and 10 days prepartum, as well as 4 and 21 days postpartum from 24 Holstein cows. Biopsies were taken immediately before and 60 min after intravenous glucose challenge causing endogenous release of insulin. Gene expression of IGF-1, myostatin, and atrogin-1, as well as immunoblot analysis of atrogin-1, muRF1, ubiquitinated proteins, LC3, and phosphorylation of AKT, ERK and mTORC1 substrate 4EBP1 was performed. Excess energy consumption in late pregnancy did not lead to changes in insulin-dependent molecular regulation of muscle accretion or atrophy compared with the controlled energy group. In both groups, phosphorylation of AKT and mTORC1 substrate was significantly decreased postpartum whereas proteasome activity and macroautopagy were upregulated. This study showed that in addition to the proteasome pathway of muscle atrophy, macroautophagy is upregulated in postpartum negative energy and protein balance regardless of dietary energy strategy prepartum and was higher in cows overfed energy throughout the study period.

  1. Microarray analysis of gene expression by skeletal muscle of three mouse models of Kennedy disease/spinal bulbar muscular atrophy.

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    Kaiguo Mo

    2010-09-01

    Full Text Available Emerging evidence implicates altered gene expression within skeletal muscle in the pathogenesis of Kennedy disease/spinal bulbar muscular atrophy (KD/SBMA. We therefore broadly characterized gene expression in skeletal muscle of three independently generated mouse models of this disease. The mouse models included a polyglutamine expanded (polyQ AR knock-in model (AR113Q, a polyQ AR transgenic model (AR97Q, and a transgenic mouse that overexpresses wild type AR solely in skeletal muscle (HSA-AR. HSA-AR mice were included because they substantially reproduce the KD/SBMA phenotype despite the absence of polyQ AR.We performed microarray analysis of lower hindlimb muscles taken from these three models relative to wild type controls using high density oligonucleotide arrays. All microarray comparisons were made with at least 3 animals in each condition, and only those genes having at least 2-fold difference and whose coefficient of variance was less than 100% were considered to be differentially expressed. When considered globally, there was a similar overlap in gene changes between the 3 models: 19% between HSA-AR and AR97Q, 21% between AR97Q and AR113Q, and 17% between HSA-AR and AR113Q, with 8% shared by all models. Several patterns of gene expression relevant to the disease process were observed. Notably, patterns of gene expression typical of loss of AR function were observed in all three models, as were alterations in genes involved in cell adhesion, energy balance, muscle atrophy and myogenesis. We additionally measured changes similar to those observed in skeletal muscle of a mouse model of Huntington's Disease, and to those common to muscle atrophy from diverse causes.By comparing patterns of gene expression in three independent models of KD/SBMA, we have been able to identify candidate genes that might mediate the core myogenic features of KD/SBMA.

  2. Effect of different flooring systems on claw conformation of dairy cows.

    Science.gov (United States)

    Telezhenko, E; Bergsten, C; Magnusson, M; Nilsson, C

    2009-06-01

    The effect of different flooring surfaces in walking and standing areas on claw conformation, claw horn growth, and wear was studied in 2 experiments during 2 consecutive housing seasons in a research dairy herd of 170 cows. In experiment 1, the flooring systems tested were solid rubber mats, mastic asphalt with and without rubber-matted feed-stalls, and aged concrete slats. In experiment 2, slatted concrete flooring was compared with slatted rubber flooring. The cows were introduced to the respective flooring systems in early lactation and their claws were trimmed before the exposure period. Toe length, toe angle, sole concavity, and claw width, as well as claw growth and wear rates were recorded for lateral and medial claws of the left hind limb. Claw asymmetry calculations were based on these claw measurements and on differences in sole protrusion between lateral and medial soles. Asphalt floors caused shorter toe length and steeper toe angle. They also increased wear on rear claws (5.30 +/- 0.31 and 5.95 +/- 0.33 mm/mo for lateral and medial claw, respectively; LSM +/- SE) and horn growth rate (5.12 +/- 0.36 and 5.83 +/- 0.31 mm/mo of lateral and medial claws, respectively). Rubber mats instead of asphalt in walking areas reduced wear (1.36 +/- 0.19 and 2.02 +/- 0.20 mm/mo for lateral and medial claw, respectively) and claw growth (3.83 +/- 0.23 and 3.94 +/- 0.17 mm/mo for lateral and medial claw, respectively). Rubber-matted feed-stalls together with asphalt walkways decreased claw wear (3.29 +/- 0.31 and 4.10 +/- 0.32 mm/mo for lateral and medial claw, respectively). The concavity of claw soles was reduced on asphalt, especially in the lateral rear claws. Rubber matting in feed-stalls prevented loss of sole concavity compared with asphalt. Claw asymmetry did not differ between flooring systems. While different access to abrasive flooring affected claw conformation, there was no evidence that flooring system influenced the disproportion between lateral and

  3. Electrophysiological Correlates of the Threshold to Detection of Passive Motion: An Investigation in Professional Volleyball Athletes with and without Atrophy of the Infraspinatus Muscle

    Science.gov (United States)

    Salles, José Inácio; Cossich, Victor Rodrigues Amaral; Amaral, Marcus Vinicius; Monteiro, Martim T.; Cagy, Maurício; Motta, Geraldo; Velasques, Bruna; Piedade, Roberto; Ribeiro, Pedro

    2013-01-01

    The goal of the present study is to compare the electrophysiological correlates of the threshold to detection of passive motion (TTDPM) among three groups: healthy individuals (control group), professional volleyball athletes with atrophy of the infraspinatus muscle on the dominant side, and athletes with no shoulder pathologies. More specifically, the study aims at assessing the effects of infraspinatus muscle atrophy on the cortical representation of the TTDPM. A proprioception testing device (PTD) was used to measure the TTDPM. The device passively moved the shoulder and participants were instructed to respond as soon as movement was detected (TTDPM) by pressing a button switch. Response latency was established as the delay between the stimulus (movement) and the response (button press). Electroencephalographic (EEG) and electromyographic (EMG) activities were recorded simultaneously. An analysis of variance (ANOVA) and subsequent post hoc tests indicated a significant difference in latency between the group of athletes without the atrophy when compared both to the group of athletes with the atrophy and to the control group. Furthermore, distinct patterns of cortical activity were observed in the three experimental groups. The results suggest that systematically trained motor abilities, as well as the atrophy of the infraspinatus muscle, change the cortical representation of the different stages of proprioceptive information processing and, ultimately, the cortical representation of the TTDPM. PMID:23484136

  4. Rates of ubiquitin conjugation increase when muscles atrophy, largely through activation of the N-end rule pathway

    Science.gov (United States)

    Solomon, V.; Baracos, V.; Sarraf, P.; Goldberg, A. L.

    1998-01-01

    The rapid loss of muscle mass that accompanies many disease states, such as cancer or sepsis, is primarily a result of increased protein breakdown in muscle, and several observations have suggested an activation of the ubiquitin-proteasome system. Accordingly, in extracts of atrophying muscles from tumor-bearing or septic rats, rates of 125I-ubiquitin conjugation to endogenous proteins were found to be higher than in control extracts. On the other hand, in extracts of muscles from hypothyroid rats, where overall proteolysis is reduced below normal, the conjugation of 125I-ubiquitin to soluble proteins decreased by 50%, and treatment with triiodothyronine (T3) restored ubiquitination to control levels. Surprisingly, the N-end rule pathway, which selectively degrades proteins with basic or large hydrophobic N-terminal residues, was found to be responsible for most of these changes in ubiquitin conjugation. Competitive inhibitors of this pathway that specifically block the ubiquitin ligase, E3alpha, suppressed most of the increased ubiquitin conjugation in the muscle extracts from tumor-bearing and septic rats. These inhibitors also suppressed ubiquitination in normal extracts toward levels in hypothyroid extracts, which showed little E3alpha-dependent ubiquitination. Thus, the inhibitors eliminated most of the differences in ubiquitination under these different pathological conditions. Moreover, 125I-lysozyme, a model N-end rule substrate, was ubiquitinated more rapidly in extracts from tumor-bearing and septic rats, and more slowly in those from hypothyroid rats, than in controls. Thus, the rate of ubiquitin conjugation increases in atrophying muscles, and these hormone- and cytokine-dependent responses are in large part due to activation of the N-end rule pathway.

  5. Claw and limb disorders in 12 Norwegian beef-cow herds.

    Science.gov (United States)

    Fjeldaas, Terje; Nafstad, Ola; Fredriksen, Bente; Ringdal, Grethe; Sogstad, Ase M

    2007-09-24

    The main aim of the study was to assess the prevalence of claw and limb disorders in Norwegian beef-cow herds. Twenty-six herds with >or=15 cow-years were selected by computerized systematic assignment from the three most beef cattle-dense regions of Norway. The study population consisted of 12 herds with 28 heifers and 334 cows. The animals were trimmed and examined once by claw trimmers during the late winter and spring of 2003. The seven claw trimmers had been taught diagnosing and recording of claw lesions. Environment, feeding and management routines, age and breed, culling and carcass characteristics were also recorded. Lameness was recorded in 1.1% of the animals, and only in hind claws. Pericarpal swellings were recorded in one animal and peritarsal lesions in none. In total, claw and limb disorders including lameness were recorded in 29.6% of the animals, 4.1% with front and 28.2% with hind limb disorders, respectively. Most lesions were mild. Laminitis-related claw lesions were recorded in 18.0% of the animals and infectious lesions in 16.6%. The average claw length was 84 mm in front claws and 89 mm in hind claw. Both laminitis-related and infectious claw lesions were more prevalent with increasing age. Carcasses from animals with claw and limb disorders were on average 34 kg heavier than carcasses from animals without such disorders (p = 0.02). Our results also indicate association between some management factors and claw lesions. The study shows that the prevalence of lameness was low in 12 Norwegian beef-cow herds compared to beef-cattle herds in other countries and also that there were less claw and limb disorders in these herds compared to foreign dairy-cattle herds. The prevalence of lameness and white-line fissures was approximately the same as in Norwegian dairy herds whereas less dermatitis, heel-horn erosions, haemorrhages of the sole and the white line and sole ulcers were recorded.

  6. Claw and limb disorders in 12 Norwegian beef-cow herds

    Directory of Open Access Journals (Sweden)

    Ringdal Grethe

    2007-09-01

    Full Text Available Abstract Background The main aim of the study was to assess the prevalence of claw and limb disorders in Norwegian beef-cow herds. Methods Twenty-six herds with ≥15 cow-years were selected by computerized systematic assignment from the three most beef cattle-dense regions of Norway. The study population consisted of 12 herds with 28 heifers and 334 cows. The animals were trimmed and examined once by claw trimmers during the late winter and spring of 2003. The seven claw trimmers had been taught diagnosing and recording of claw lesions. Environment, feeding and management routines, age and breed, culling and carcass characteristics were also recorded. Results Lameness was recorded in 1.1% of the animals, and only in hind claws. Pericarpal swellings were recorded in one animal and peritarsal lesions in none. In total, claw and limb disorders including lameness were recorded in 29.6% of the animals, 4.1% with front and 28.2% with hind limb disorders, respectively. Most lesions were mild. Laminitis-related claw lesions were recorded in 18.0% of the animals and infectious lesions in 16.6%. The average claw length was 84 mm in front claws and 89 mm in hind claw. Both laminitis-related and infectious claw lesions were more prevalent with increasing age. Carcasses from animals with claw and limb disorders were on average 34 kg heavier than carcasses from animals without such disorders (p = 0.02. Our results also indicate association between some management factors and claw lesions. Conclusion The study shows that the prevalence of lameness was low in 12 Norwegian beef-cow herds compared to beef-cattle herds in other countries and also that there were less claw and limb disorders in these herds compared to foreign dairy-cattle herds. The prevalence of lameness and white-line fissures was approximately the same as in Norwegian dairy herds whereas less dermatitis, heel-horn erosions, haemorrhages of the sole and the white line and sole ulcers were

  7. Severe muscle atrophy due to spinal cord injury can be reversed in complete absence of peripheral nerves

    Directory of Open Access Journals (Sweden)

    Simona Boncompagni

    2012-12-01

    Full Text Available In the last years, a new efficient treatment has been developed to treat paralyzed skeletal muscle of patients affected by spinal cord injury (SCI. The capability of the functional electrical stimulation (FES to improve trophism and in some cases muscle function, are now well documented both in animals after experimental cord lesion, and in humans, generally after traumatic cord lesion. This new findings makes FES an important tool for the rehabilitation of SCI patients. FES stimulation has been proven to be an effective method used to retard muscle atrophy and improve recovery after reinnervation. Sophisticated FES devices have been developed for restoring function in the upper and lower extremities, the bladder and bowel, and the respiratory system of SCI patients. However, there are SCI cases, such as those affected by flaccid paralysis, in which the musculature is not treated with FES rehabilitation therapy. This is because conventional FES apparatuses are designed for direct stimulation of peripheral nerves that need small currents to be depolarized, and are not effective in patients that have lost their peripheral nerves, and, therefore, require higher currents for the direct depolarization of the muscle fibers. Lack of muscle treatment generates, as a secondary problem, a long series of alterations to tissues other than muscle, such as bones (osteoporosis, skin (pressure sores, decubital ulcers, etc., that are a direct consequence of inactivity and poor blood supply to the denervated areas. These complications represent an extremely serious problem for the general health of the injured individuals, who usually have a shorter than normal life span. In the hopes of changing this common belief, an innovative rehabilitation procedure, based on FES, has been developed with the aim of reversing long-lasting muscle atrophy in the muscles of the lower extremities of SCI patients affected by complete lesion of the conus cauda, i.e. that have no

  8. Isolated and painless (? atrophy of the infraspinatus muscle: left handed versus right handed volleyball players

    Directory of Open Access Journals (Sweden)

    Thiago D. Gonçalves Côelho

    1994-12-01

    Full Text Available The suprascapular nerve originates from the upper trunk of the brachial plexus or less frequently from the root of C5. It runs a short way and crosses the suprascapular notch. It innervates the supraspinatus muscle and the acromioclavicular and glenohumeral joints. Then, it crosses the lateral edge of the spine of the scapula passing through the spinoglenoid notch, and innervates the infraspinatus muscle. These are potential sites of injury to the suprascapular nerve. Three cases of suprascapular nerve entrapment causing an isolated infraspinatus muscle atrophy in volleyball players were studied. It is suggested the hypothesis that the nature of the smash, in which the athlete uses the arm violently, more than does in volleyball service or in the art of reception, is the key to the pathogenesis of the lesion in volleyball players.

  9. HDAC4-Myogenin Axis As an Important Marker of HD-Related Skeletal Muscle Atrophy

    Science.gov (United States)

    Smeets, Cleo J. L. M.; Franklin, Sophie A.; Bondulich, Marie K.; Jolinon, Nelly; Muller, Thomas; Ahmed, Mhoriam; Dick, James R. T.; Piotrowska, Izabela; Greensmith, Linda; Smolenski, Ryszard T.; Bates, Gillian P.

    2015-01-01

    Skeletal muscle remodelling and contractile dysfunction occur through both acute and chronic disease processes. These include the accumulation of insoluble aggregates of misfolded amyloid proteins that is a pathological feature of Huntington’s disease (HD). While HD has been described primarily as a neurological disease, HD patients’ exhibit pronounced skeletal muscle atrophy. Given that huntingtin is a ubiquitously expressed protein, skeletal muscle fibres may be at risk of a cell autonomous HD-related dysfunction. However the mechanism leading to skeletal muscle abnormalities in the clinical and pre-clinical HD settings remains unknown. To unravel this mechanism, we employed the R6/2 transgenic and HdhQ150 knock-in mouse models of HD. We found that symptomatic animals developed a progressive impairment of the contractile characteristics of the hind limb muscles tibialis anterior (TA) and extensor digitorum longus (EDL), accompanied by a significant loss of motor units in the EDL. In symptomatic animals, these pronounced functional changes were accompanied by an aberrant deregulation of contractile protein transcripts and their up-stream transcriptional regulators. In addition, HD mouse models develop a significant reduction in muscle force, possibly as a result of a deterioration in energy metabolism and decreased oxidation that is accompanied by the re-expression of the HDAC4-DACH2-myogenin axis. These results show that muscle dysfunction is a key pathological feature of HD. PMID:25748626

  10. Supplementation of Magnolol Attenuates Skeletal Muscle Atrophy in Bladder Cancer-Bearing Mice Undergoing Chemotherapy via Suppression of FoxO3 Activation and Induction of IGF-1.

    Directory of Open Access Journals (Sweden)

    Meng-Chuan Chen

    Full Text Available Skeletal muscle atrophy, the most prominent phenotypic feature of cancer cachexia, is often observed in cancer patients undergoing chemotherapy. Magnolol (M extracted from Magnolia officinalis exhibits several pharmacological effects including anti-inflammatory and anticancer activities. In this study, we investigated whether magnolol supplementation protects against the development of cachexia symptoms in bladder cancer-bearing mice undergoing chemotherapy. Combined treatment of magnolol with chemotherapeutic drugs, such as gemcitabine and cisplatin (TGCM or gemcitabine (TGM, markedly attenuates the body weight loss and skeletal muscle atrophy compared with conventional chemotherapy (TGC. The antiatrophic effect of magnolol may be associated with inhibition of myostatin and activin A formation, as well as FoxO3 transcriptional activity resulting from Akt activation, thereby suppressing ubiquitin ligases MuRF-1 and MAFbx/atrogin-1 expression, as well as proteasomal enzyme activity. Notably, magnolol-induced insulin-like growth factor 1 (IGF-1 production and related protein synthesis may also contribute to its protective effects. The decreased food intake, and intestinal injury and dysfunction observed in the mice of TGC group were significantly improved in the TGCM and TGM groups. Moreover, the increased inflammatory responses evidenced by elevation of proinflammatory cytokine formation and NF-κB activation occurred in the atrophying muscle of TGC group were markedly inhibited in mice of combined treatment with magnolol. In summary, these findings support that magnolol is a promising chemopreventive supplement for preventing chemotherapy-induced skeletal muscle atrophy associated with cancer cachexia by suppressing muscle protein degradation, and inflammatory responses, as well as increasing IGF-1-mediated protein synthesis.

  11. Muscle atrophy

    Science.gov (United States)

    ... People who cannot actively move one or more joints can do exercises using braces or splints . When ... A.M. Editorial team. Muscle Disorders Read more Neuromuscular Disorders Read more NIH MedlinePlus Magazine Read more ...

  12. Muscle MRI STIR signal intensity and atrophy are correlated to focal lower limb neuropathy severity.

    Science.gov (United States)

    Deroide, N; Bousson, V; Mambre, L; Vicaut, E; Laredo, J D; Kubis, Nathalie

    2015-03-01

    The objective is to determine if muscle MRI is useful for assessing neuropathy severity. Clinical, MRI and electromyography (EMG) examinations were performed in 17 patients with focal lower limb neuropathies. MRI Short Tau Inversion Recovery (STIR) signal intensity, amyotrophy, and muscle fatty infiltration measured after T1-weighted image acquisition, EMG spontaneous activity (SA), and maximal voluntary contraction (MVC) were graded using semiquantitative scores and quantitative scores for STIR signal intensity and were correlated to the Medical Research Council (MRC) score for testing muscle strength. Within this population, subgroups were selected according to severity (mild versus severe), duration (subacute versus chronic), and topography (distal versus proximal) of the neuropathy. EMG SA and MVC MRI amyotrophy and quantitative scoring of muscle STIR intensity were correlated with the MRC score. Moreover, MRI amyotrophy was significantly increased in severe, chronic, and proximal neuropathies along with fatty infiltration in chronic lesions. Muscle MRI atrophy and quantitative evaluation of signal intensity were correlated to MRC score in our study. Semiquantitative evaluation of muscle STIR signal was sensitive enough for detection of topography of the nerve lesion but was not suitable to assess severity. Muscle MRI could support EMG in chronic and proximal neuropathy, which showed poor sensitivity in these patients.

  13. Muscle MRI STIR signal intensity and atrophy are correlated to focal lower limb neuropathy severity

    Energy Technology Data Exchange (ETDEWEB)

    Deroide, N.; Mambre, L.; Kubis, Nathalie [Service de Physiologie Clinique-Explorations Fonctionnelles, AP-HP, Hopital Lariboisiere, Paris (France); Universite Paris Diderot, Sorbonne Paris Cite France, Paris (France); Bousson, V.; Laredo, J.D. [Universite Paris Diderot, Sorbonne Paris Cite France, Paris (France); Radiologie Osteo-articulaire, AP-HP, Hopital Lariboisiere, Paris (France); Vicaut, E. [Universite Paris Diderot, Sorbonne Paris Cite France, Paris (France); URC, AP-HP, Hopital Lariboisiere, Paris (France)

    2014-09-26

    The objective is to determine if muscle MRI is useful for assessing neuropathy severity. Clinical, MRI and electromyography (EMG) examinations were performed in 17 patients with focal lower limb neuropathies. MRI Short Tau Inversion Recovery (STIR) signal intensity, amyotrophy, and muscle fatty infiltration measured after T1-weighted image acquisition, EMG spontaneous activity (SA), and maximal voluntary contraction (MVC) were graded using semiquantitative scores and quantitative scores for STIR signal intensity and were correlated to the Medical Research Council (MRC) score for testing muscle strength. Within this population, subgroups were selected according to severity (mild versus severe), duration (subacute versus chronic), and topography (distal versus proximal) of the neuropathy. EMG SA and MVC MRI amyotrophy and quantitative scoring of muscle STIR intensity were correlated with the MRC score. Moreover, MRI amyotrophy was significantly increased in severe, chronic, and proximal neuropathies along with fatty infiltration in chronic lesions. Muscle MRI atrophy and quantitative evaluation of signal intensity were correlated to MRC score in our study. Semiquantitative evaluation of muscle STIR signal was sensitive enough for detection of topography of the nerve lesion but was not suitable to assess severity. Muscle MRI could support EMG in chronic and proximal neuropathy, which showed poor sensitivity in these patients. (orig.)

  14. Morphological and functional diversity in therizinosaur claws and the implications for theropod claw evolution.

    Science.gov (United States)

    Lautenschlager, Stephan

    2014-06-22

    Therizinosaurs are a group of herbivorous theropod dinosaurs from the Cretaceous of North America and Asia, best known for their iconically large and elongate manual claws. However, among Therizinosauria, ungual morphology is highly variable, reflecting a general trend found in derived theropod dinosaurs (Maniraptoriformes). A combined approach of shape analysis to characterize changes in manual ungual morphology across theropods and finite-element analysis to assess the biomechanical properties of different ungual shapes in therizinosaurs reveals a functional diversity related to ungual morphology. While some therizinosaur taxa used their claws in a generalist fashion, other taxa were functionally adapted to use the claws as grasping hooks during foraging. Results further indicate that maniraptoriform dinosaurs deviated from the plesiomorphic theropod ungual morphology resulting in increased functional diversity. This trend parallels modifications of the cranial skeleton in derived theropods in response to dietary adaptation, suggesting that dietary diversification was a major driver for morphological and functional disparity in theropod evolution.

  15. Respiratory muscle function in infants with spinal muscular atrophy type I.

    Science.gov (United States)

    Finkel, Richard S; Weiner, Daniel J; Mayer, Oscar H; McDonough, Joseph M; Panitch, Howard B

    2014-12-01

    To determine the feasibility and safety of respiratory muscle function testing in weak infants with a progressive neuromuscular disorder. Respiratory insufficiency is the major cause of morbidity and mortality in infants with spinal muscular atrophy type I (SMA-I). Tests of respiratory muscle strength, endurance, and breathing patterns can be performed safely in SMA-I infants. Useful data can be collected which parallels the clinical course of pulmonary function in SMA-I. An exploratory study of respiratory muscle function testing and breathing patterns in seven infants with SMA-I seen in our neuromuscular clinic. Measurements were made at initial study visit and, where possible, longitudinally over time. We measured maximal inspiratory (MIP) and transdiaphragmatic pressures, mean transdiaphragmatic pressure, airway occlusion pressure at 100 msec of inspiration, inspiratory and total respiratory cycle time, and aspects of relative thoracoabdominal motion using respiratory inductive plethysmography (RIP). The tension time index of the diaphragm and of the respiratory muscles, phase angle (Φ), phase relation during the total breath, and labored breathing index were calculated. Age at baseline study was 54-237 (median 131) days. Reliable data were obtained safely for MIP, phase angle, labored breathing index, and the invasive and non-invasive tension time indices, even in very weak infants. Data obtained corresponded to the clinical estimate of severity and predicted the need for respiratory support. The testing employed was both safe and feasible. Measurements of MIP and RIP are easily performed tests that are well tolerated and provide clinically useful information for infants with SMA-I. © 2014 Wiley Periodicals, Inc.

  16. IGF-1 prevents ANG II-induced skeletal muscle atrophy via Akt- and Foxo-dependent inhibition of the ubiquitin ligase atrogin-1 expression

    Science.gov (United States)

    Yoshida, Tadashi; Semprun-Prieto, Laura; Sukhanov, Sergiy

    2010-01-01

    Congestive heart failure is associated with activation of the renin-angiotensin system and skeletal muscle wasting. Angiotensin II (ANG II) has been shown to increase muscle proteolysis and decrease circulating and skeletal muscle IGF-1. We have shown previously that skeletal muscle-specific overexpression of IGF-1 prevents proteolysis and apoptosis induced by ANG II. These findings indicated that downregulation of IGF-1 signaling in skeletal muscle played an important role in the wasting effect of ANG II. However, the signaling pathways and mechanisms whereby IGF-1 prevents ANG II-induced skeletal muscle atrophy are unknown. Here we show ANG II-induced transcriptional regulation of two ubiquitin ligases atrogin-1 and muscle ring finger-1 (MuRF-1) that precedes the reduction of skeletal muscle IGF-1 expression, suggesting that activation of atrogin-1 and MuRF-1 is an initial mechanism leading to skeletal muscle atrophy in response to ANG II. IGF-1 overexpression in skeletal muscle prevented ANG II-induced skeletal muscle wasting and the expression of atrogin-1, but not MuRF-1. Dominant-negative Akt and constitutively active Foxo-1 blocked the ability of IGF-1 to prevent ANG II-mediated upregulation of atrogin-1 and skeletal muscle wasting. Our findings demonstrate that the ability of IGF-1 to prevent ANG II-induced skeletal muscle wasting is mediated via an Akt- and Foxo-1-dependent signaling pathway that results in inhibition of atrogin-1 but not MuRF-1 expression. These data suggest strongly that atrogin-1 plays a critical role in mechanisms of ANG II-induced wasting in vivo. PMID:20228261

  17. Vortex formation with a snapping shrimp claw.

    Science.gov (United States)

    Hess, David; Brücker, Christoph; Hegner, Franziska; Balmert, Alexander; Bleckmann, Horst

    2013-01-01

    Snapping shrimp use one oversized claw to generate a cavitating high speed water jet for hunting, defence and communication. This work is an experimental investigation about the jet generation. Snapping shrimp (Alpheus-bellulus) were investigated by using an enlarged transparent model reproducing the closure of the snapper claw. Flow inside the model was studied using both High-Speed Particle Image Velocimetry (HS-PIV) and flow visualization. During claw closure a channel-like cavity was formed between the plunger and the socket featuring a nozzle-type contour at the orifice. Closing the mechanism led to the formation of a leading vortex ring with a dimensionless formation number of approximate ΔT*≈4. This indicates that the claw might work at maximum efficiency, i.e. maximum vortex strength was achieved by a minimum of fluid volume ejected. The subsequent vortex cavitation with the formation of an axial reentrant jet is a reasonable explanation for the large penetration depth of the water jet. That snapping shrimp can reach with their claw-induced flow. Within such a cavitation process, an axial reentrant jet is generated in the hollow cylindrical core of the cavitated vortex that pushes the front further downstream and whose length can exceed the initial jet penetration depth by several times.

  18. Vortex formation with a snapping shrimp claw.

    Directory of Open Access Journals (Sweden)

    David Hess

    Full Text Available Snapping shrimp use one oversized claw to generate a cavitating high speed water jet for hunting, defence and communication. This work is an experimental investigation about the jet generation. Snapping shrimp (Alpheus-bellulus were investigated by using an enlarged transparent model reproducing the closure of the snapper claw. Flow inside the model was studied using both High-Speed Particle Image Velocimetry (HS-PIV and flow visualization. During claw closure a channel-like cavity was formed between the plunger and the socket featuring a nozzle-type contour at the orifice. Closing the mechanism led to the formation of a leading vortex ring with a dimensionless formation number of approximate ΔT*≈4. This indicates that the claw might work at maximum efficiency, i.e. maximum vortex strength was achieved by a minimum of fluid volume ejected. The subsequent vortex cavitation with the formation of an axial reentrant jet is a reasonable explanation for the large penetration depth of the water jet. That snapping shrimp can reach with their claw-induced flow. Within such a cavitation process, an axial reentrant jet is generated in the hollow cylindrical core of the cavitated vortex that pushes the front further downstream and whose length can exceed the initial jet penetration depth by several times.

  19. The role of myostatin and activin receptor IIB in the regulation of unloading-induced myofiber type-specific skeletal muscle atrophy.

    Science.gov (United States)

    Babcock, Lyle W; Knoblauch, Mark; Clarke, Mark S F

    2015-09-15

    Chronic unloading induces decrements in muscle size and strength. This adaptation is governed by a number of molecular factors including myostatin, a potent negative regulator of muscle mass. Myostatin must first be secreted into the circulation and then bind to the membrane-bound activin receptor IIB (actRIIB) to exert its atrophic action. Therefore, we hypothesized that myofiber type-specific atrophy observed after hindlimb suspension (HLS) would be related to myofiber type-specific expression of myostatin and/or actRIIB. Wistar rats underwent HLS for 10 days, after which the tibialis anterior was harvested for frozen cross sectioning. Simultaneous multichannel immunofluorescent staining combined with differential interference contrast imaging was employed to analyze myofiber type-specific expression of myostatin and actRIIB and myofiber type cross-sectional area (CSA) across fiber types, myonuclei, and satellite cells. Hindlimb suspension (HLS) induced significant myofiber type-specific atrophy in myosin heavy chain (MHC) IIx (P Myostatin staining associated with myonuclei was less in HLS rats compared with controls, while satellite cell staining for myostatin remained unchanged. In contrast, the total number myonuclei and satellite cells per myofiber was reduced in HLS compared with ambulatory control rats (P myostatin-induced myofiber type-selective atrophy observed during chronic unloading. Copyright © 2015 the American Physiological Society.

  20. Milking performance evaluation and factors affecting milking claw vacuum levels with flow simulator.

    Science.gov (United States)

    Enokidani, Masafumi; Kawai, Kazuhiro; Shinozuka, Yasunori; Watanabe, Aiko

    2017-08-01

    Milking performance of milking machines that matches the production capability of dairy cows is important in reducing the risk of mastitis, particularly in high-producing cows. This study used a simulated milking device to examine the milking performance of the milking system of 73 dairy farms and to analyze the factors affecting claw vacuum. Mean claw vacuum and range of fluctuation of claw vacuum (claw vacuum range) were measured at three different flow rates: 5.7, 7.6 and 8.7 kg/min. At the highest flow rate, only 16 farms (21.9%) met both standards of mean claw vacuum ≥35 kPa and claw vacuum range ≤ 7 kPa, showing that milking systems currently have poor milking performance. The factors affecting mean claw vacuum were claw type, milk-meter and vacuum shut-off device; the factor affecting claw vacuum range was claw type. Examination of the milking performance of the milking system using a simulated milking device allows an examination of the performance that can cope with high producing cows, indicating the possibility of reducing the risk of mastitis caused by inappropriate claw vacuum. © 2016 Japanese Society of Animal Science.

  1. Forkhead box O3 plays a role in skeletal muscle atrophy through expression of E3 ubiquitin ligases MuRF-1 and atrogin-1 in Cushing's syndrome.

    Science.gov (United States)

    Kang, Seol-Hee; Lee, Hae-Ahm; Kim, Mina; Lee, Eunjo; Sohn, Uy Dong; Kim, Inkyeom

    2017-06-01

    Cushing's syndrome is caused by overproduction of the adrenocorticotropic hormone (ACTH), which stimulates the adrenal grand to make cortisol. Skeletal muscle wasting occurs in pathophysiological response to Cushing's syndrome. The forkhead box (FOX) protein family has been implicated as a key regulator of muscle loss under conditions such as diabetes and sepsis. However, the mechanistic role of the FOXO family in ACTH-induced muscle atrophy is not understood. We hypothesized that FOXO3a plays a role in muscle atrophy through expression of the E3 ubiquitin ligases, muscle RING finger protein-1 (MuRF-1), and atrogin-1 in Cushing's syndrome. For establishment of a Cushing's syndrome animal model, Sprague-Dawley rats were implanted with osmotic minipumps containing ACTH (40 ng·kg -1 ·day -1 ). ACTH infusion significantly reduced muscle weight. In ACTH-infused rats, MuRF-1, atrogin-1, and FOXO3a were upregulated and the FOXO3a promoter was targeted by the glucocorticoid receptor (GR). Transcriptional activity and expression of FOXO3a were significantly decreased by the GR antagonist RU486. Treatment with RU486 reduced MuRF-1 and atrogin-1 expression in accordance with reduced enrichment of FOXO3a and Pol II on the promoters. Knockdown of FOXO3a prevented dexamethasone-induced MuRF-1 and atrogin-1 expression. These results indicate that FOXO3a plays a role in muscle atrophy through expression of MuRF-1 and atrogin-1 in Cushing's syndrome. Copyright © 2017 the American Physiological Society.

  2. [Effect of gravitation loading and retabolil on development of atrophy in muscles and bones of rats due to suspension].

    Science.gov (United States)

    KaplanskiI, A S; Il'ina-Kakueva, E I; Durnova, G N; Alekseev, E A; Loginov, V I

    1999-01-01

    In a 3-wk experiment with tail-suspended rats histological and histomorphometric methods were used to determine the effects of graded gravitational loading (GGL) and anabolic steroid retabolil (nortestosterone decanoate) on the course of atrophy in soleus m. (SM), gastrocnemius m. (GM), tibia and humerus, and functioning of somatotrophic hormones (STH) of the pituitary and thyrocytes of the thyroid. Suspension was found to produce atrophy in SM and, to a less degree, in GM, partial transformation of SM slow fibers into the fast ones, suppression of the tibial longitudinal growth, demineralization of the tibial and humeral spongious metaphyses; besides, functional activities of STH-cells and thyrocytes were inhibited. Graded gravitational loading of rats by intermittence of suspension for 2 hrs slowed down atrophy in both muscles and osteopenia in tibia, stimulated the synthetic and secretory functions of STH-cells without any marked effect on thyrocytes or humeral osteopenia. GGL failed to influence the slow-to-fast transformation of SM fibers. Two injections of retabolil at the total dose of 3 mg/kg of the body mass somewhat interfered with the SM atrophy and humoral osteopenia, and were favorable to the synthetic but not secretory activity of STH-cells. Neither SM and tibial atrophies nor thyroid activity of the gland were improved. The prophylactic action of GGL upon the SM and humeral atrophies was significantly higher when combined with retabolil, whereas GM and tibia were not noticeably cured by retabolil. Inhibition of the SM atrophy and humeral osteopenia in rats treated with GGL and retabolil concurred with elevated activities of STH-cells and thyrocytes indirectly suggesting their more intensive production of the growth hormone and thyroid hormones, respectively.

  3. Spinal Muscular Atrophy FAQ

    Science.gov (United States)

    ... as ALS (Lou Gehrig’s Disease), cystic fibrosis and Duchenne muscular dystrophy. Approximately 1 in 50 Americans, or about 6 ... Pediatric Neuromuscular Clinical Research Network ( PNCR ) and the Muscular ... is the SMN2 gene? Muscle weakness and atrophy in SMA results from the ...

  4. Ipsilateral atrophy of the psoas major muscle in patients with lumbar disc herniation

    International Nuclear Information System (INIS)

    Makino, Takahiro; Hosono, Noboru; Mukai, Yoshihiro; Miwa, Toshitada; Fuji, Takeshi

    2009-01-01

    We measured the cross-sectional area (CSA) of the psoas major muscles of 48 male patients under 50 years of age with unilateral sciatica caused by a single-level lumbar disc herniation. Patients who had multi-level disc lesions, lumbar canal stenosis, spondylolisthesis, scoliosis>5deg, or a history of lumbar surgery or hip joint disease were excluded. Mean age at surgery was 33 years old. Two orthopedic surgeons measured the CSA independently and blindly on magnetic resonance images in which the spinal canal had been blacked out. The CSA ratio (pain-positive side/pain-negative side) was 0.99 at L3/4, 0.98 at L4/5, and 1.00 at L5/S. There was a statistically significant difference between the CSA of the psoas major muscle on the painful side and the unaffected side at L4/5 (p=0.02). There was no correlation between the CSA ratio and the angle in the straight leg raising test, the duration of symptoms, or the size of the disc herniation. The atrophy of the psoas major muscle observed on the pain-positive side in lumbar disc herniation patients may be attributable to disuse of the affected leg. (author)

  5. [Claw size of Scottish Highland Cows after pasture and housing periods].

    Science.gov (United States)

    Nuss, K; Kolp, E; Braun, U; Weidmann, E; Hässig, M

    2014-09-01

    The claws of pastured Scottish Highland Cattle are large and this may raise the question if regular claw trimming is necessary. Therefore, the claws of the right thoracic and pelvic limbs were measured in 22 Scottish Highland cows 4 times 8 weeks apart. The cows were kept on various alpine pastures before the first measurement, on a two-hectare low-land pasture before the second measurement, in a welfare-compliant straw-bedded free stall before the third measurement and on alpine pasture before the fourth measurement. Housing conditions significantly affected claw dimensions. The claws were composed of dry, hard horn during pasture periods, and had prominent weight-bearing hoof-wall borders and soles with a natural axial slope. Long dorsal walls and heels and a greater symmetry were common. Claw lesions were absent. In contrast, free-stall housing was associated with shorter toes and steeper toe angles, but white line deterioration, heel horn erosion, wearing of the axial slope and hoof wall edges were common.

  6. Genetic correlations between claw health and feet and leg conformation in Norwegian Red cows.

    Science.gov (United States)

    Ødegård, C; Svendsen, M; Heringstad, B

    2014-07-01

    The aim of this study was to estimate genetic correlations between claw disorders and feet and leg conformation traits in Norwegian Red cows. A total of 188,928 cows with claw health status recorded at claw trimming from 2004 to September 2013 and 210,789 first-lactation cows with feet and leg conformation scores from 2001 to September 2013 were included in the analyses. Traits describing claw health were corkscrew claw, infectious claw disorders (dermatitis, heel horn erosion, and interdigital phlegmon), and laminitis-related claw disorders (sole ulcer, white line disorder, and hemorrhage of sole and white line). The feet and leg conformation traits were rear leg rear view (new and old definition), rear leg side view, foot angle, and hoof quality. Feet and leg conformation traits were scored linearly from 1 to 9, with optimum scores depending on the trait. Claw disorders were defined as binary (0/1) traits for each lactation. Threshold sire models were used to model claw disorders, whereas the feet and leg conformation traits were described by linear sire models. Three multivariate analyses were performed, each including the 5 feet and leg conformation traits and 1 of the 3 claw disorders at a time. Posterior means of heritability of liability of claw disorders ranged from 0.10 to 0.20 and heritabilities of feet and leg conformation traits ranged from 0.04 to 0.11. Posterior standard deviation of heritability was ≤0.01 for all traits. Genetic correlations between claw disorders and feet and leg conformation traits were all low or moderate, except between corkscrew claw and hoof quality (-0.86), which are supposed to measure the same trait. The genetic correlations between rear leg rear view (new) and infectious claw disorders (-0.20) and laminitis-related claw disorders (0.26), and between hoof quality and laminitis-related claw disorders (-0.33) were moderate. Eight of the 15 genetic correlations between claw disorders and feet and leg conformation traits had 0

  7. Potential of laryngeal muscle regeneration using induced pluripotent stem cell-derived skeletal muscle cells.

    Science.gov (United States)

    Dirja, Bayu Tirta; Yoshie, Susumu; Ikeda, Masakazu; Imaizumi, Mitsuyoshi; Nakamura, Ryosuke; Otsuki, Koshi; Nomoto, Yukio; Wada, Ikuo; Hazama, Akihiro; Omori, Koichi

    2016-01-01

    Conclusion Induced pluripotent stem (iPS) cells may be a new potential cell source for laryngeal muscle regeneration in the treatment of vocal fold atrophy after recurrent laryngeal nerve paralysis. Objectives Unilateral vocal fold paralysis can lead to degeneration, atrophy, and loss of force of the thyroarytenoid muscle. At present, there are some treatments such as thyroplasty, arytenoid adduction, and vocal fold injection. However, such treatments cannot restore reduced mass of the thyroarytenoid muscle. iPS cells have been recognized as supplying a potential resource for cell transplantation. The aim of this study was to assess the effectiveness of the use of iPS cells for the regeneration of laryngeal muscle through the evaluation of both in vitro and in vivo experiments. Methods Skeletal muscle cells were generated from tdTomato-labeled iPS cells using embryoid body formation. Differentiation into skeletal muscle cells was analyzed by gene expression and immunocytochemistry. The tdTomato-labeled iPS cell-derived skeletal muscle cells were transplanted into the left atrophied thyroarytenoid muscle. To evaluate the engraftment of these cells after transplantation, immunohistochemistry was performed. Results The tdTomato-labeled iPS cells were successfully differentiated into skeletal muscle cells through an in vitro experiment. These cells survived in the atrophied thyroarytenoid muscle after transplantation.

  8. Genetic background of claw health in dairy cattle

    NARCIS (Netherlands)

    Spek, van der D.

    2015-01-01

    Abstract

    Van der Spek, D. (2015). Genetic background of claw health in dairy cattle. PhD thesis, Wageningen University, the Netherlands.

    Claw disorders affect cow welfare and profitability of farms and as such are important traits relevant to dairy cattle breeding.

  9. The molecular responses of skeletal muscle satellite cells to continuous expression of IGF-1: implications for the rescue of induced muscular atrophy in aged rats

    Science.gov (United States)

    Chakravarthy, M. V.; Booth, F. W.; Spangenburg, E. E.

    2001-01-01

    Approximately 50% of humans older than 85 years have physical frailty due to weak skeletal muscles. This indicates a need for determining mechanisms to combat this problem. A critical cellular factor for postnatal muscle growth is a population of myogenic precursor cells called satellite cells. Given the complex process of sarcopenia, it has been postulated that, at some point in this process, a limited satellite cell proliferation potential could become rate-limiting to the regrowth of old muscles. It is conceivable that if satellite cell proliferative capacity can be maintained or enhanced with advanced age, sarcopenia could potentially be delayed or prevented. Therefore, the purposes of this paper are to describe whether IGF-I can prevent muscular atrophy induced by repeated cycles of hindlimb immobilization, increase the in vitro proliferation in satellite cells from these muscles and, if so, the molecular mechanisms by which IGF-I mediates this increased proliferation. Our results provide evidence that IGF-I can enhance aged muscle regrowth possibly through increased satellite cell proliferation. The results also suggest that IGF-I enhances satellite cell proliferation by decreasing the cell cycle inhibitor, p27Kip1, through the PI3'-K/Akt pathway. These data provide molecular evidence for IGF-I's rescue effect upon aging-associated skeletal muscle atrophy.

  10. Genetic parameters for claw disorders and the effect of preselecting cows for trimming.

    Science.gov (United States)

    van der Spek, D; van Arendonk, J A M; Vallée, A A A; Bovenhuis, H

    2013-09-01

    Claw disorders are important traits relevant to dairy cattle breeding from an economical and welfare point of view. Selection for reduced claw disorders can be based on hoof trimmer records. Typically, not all cows in a herd are trimmed. Our objectives were to estimate heritabilities and genetic correlations for claw disorders and investigate the effect of selecting cows for trimming. The data set contained 50,238 cows, of which 20,474 cows had at least one claw trimming record, with a total of 29,994 records. Six claw trimmers scored 14 different claw disorders: abscess (AB), corkscrew claw (CC), (inter-)digital dermatitis or heel erosion (DER), double sole (DS), hardship groove (HG), interdigital hyperplasia (IH), interdigital phlegmon (IP), sand crack (SC), super-foul (SF), sole hemorrhage (SH), sole injury (SI), sole ulcer (SU), white line separation (WLS), yellow discoloration of the sole (YD), and a combined claw disorder trait. Frequencies of the claw disorders for trimmed cows ranged from 0.1% (CC, YD, HG) to 23.8% (DER). More than half of the cows scored had at least one claw disorder. Heritability on the observed scale ranged from 0.02 (DS, SH) to 0.14 (IH) and on the underlying scale from 0.05 to 0.43 in trimmed cows. Genetic correlations between laminitis-related claw disorders were moderate to high, and the same was found for hygiene-related claw disorders. The effect of selecting cows for trimming was first investigated by including untrimmed cows in the analyses and assuming they were not affected by claw disorders. Heritabilities on the underlying scale showed only minor changes. Second, different subsets of the data were created based on the percentage of trimmed cows in the herd. Heritabilities for IH, DER, and SU tended to decrease when a higher percentage of cows in the herd were trimmed. Finally, a bivariate model with a claw disorder and the trait "trimming status" was used, but heritabilities were similar. Heritability for trimming status was

  11. Bionic Design for Mars Sampling Scoop Inspired by Himalayan Marmot Claw

    Directory of Open Access Journals (Sweden)

    Long Xue

    2016-01-01

    Full Text Available Cave animals are often adapted to digging and life underground, with claw toes similar in structure and function to a sampling scoop. In this paper, the clawed toes of the Himalayan marmot were selected as a biological prototype for bionic research. Based on geometric parameter optimization of the clawed toes, a bionic sampling scoop for use on Mars was designed. Using a 3D laser scanner, the point cloud data of the second front claw toe was acquired. Parametric equations and contour curves for the claw were then built with cubic polynomial fitting. We obtained 18 characteristic curve equations for the internal and external contours of the claw. A bionic sampling scoop was designed according to the structural parameters of Curiosity’s sampling shovel and the contours of the Himalayan marmot’s claw. Verifying test results showed that when the penetration angle was 45° and the sampling speed was 0.33 r/min, the bionic sampling scoops’ resistance torque was 49.6% less than that of the prototype sampling scoop. When the penetration angle was 60° and the sampling speed was 0.22 r/min, the resistance torque of the bionic sampling scoop was 28.8% lower than that of the prototype sampling scoop.

  12. Histological analysis of thelohaniasis in white-clawed crayfish Austropotamobius pallipes complex

    Directory of Open Access Journals (Sweden)

    Quaglio F.

    2011-09-01

    Full Text Available From 2004 to 2006, a parasitological survey aimed at the detection of the microsporidian parasite Thelohania contejeani Henneguy was carried out on 177 wild white-clawed crayfish (Austropotamobius pallipes complex captured in six streams and rivers of the province of Belluno in north-eastern Italy. Microscopical examination of the skeletal muscles, and histological analysis applying different histochemical stains to full transverse and sagittal sections of the cephalothorax and abdomen were carried out. Transmission electron microscopy (TEM was also conducted on the parasites recovered during the survey. Out of 177 crayfish examined, Thelohania contejeani (Microsporidia, Thelohaniidae was present in only one crayfish from the Vena d’oro creek. The parasite was detected in the skeletal muscles in several developmental stages, including mature spores, which represented the most common stage recovered. Sporophorous vesicles were also present. Histological examination revealed that the fibres of the skeletal, cardiac and intestinal muscles were filled with spores. Melanin infiltrations were focally present in the infected striated muscles. The gill phagocytic nephrocytes were engulfed by small masses of spores. Among the staining techniques applied, Crossman’s trichrome stain represented the most effective method of detecting T. contejeani.

  13. [Role of growth hormone underproduction and support load deficit in development of muscle atrophy and osteopenia in tail-suspended rats].

    Science.gov (United States)

    Kaplanskiĭ, A S; Durnova, G N; Ili'ina-Kakueva, E I; Loginov, V I

    1999-01-01

    In a 20-day experiment with tail-suspended male rats histological and histomorphometric techniques were used to study the effects of growth hormone, thyroxin, and graded support loads on the progress of atrophy in soleus and gastrocnemius m.m., tibial metaphyses spongiosis, and growth of tibiae. Daily injections of growth hormone at a dose of 0.5 mg/kg of the body mass were found to restore the longitudinal growth of tibiae and to suppress osteopenia in the spongiosis of metaphyses; however, they did not have any noteworthy effect on the muscular atrophy in the suspended rats. Support loading of the hind limbs for 2 hours a day in parallel to the treatment with growth hormone and thyroxin (0.02 mg/kg of the body mass per a day) suppressed the atrophy in soleus m. but not in gastrocnemius m. They were not able to oppose to osteoporosis in tibial metaphyses spongiosis; tibial growth was not normalized. Thyroxin did not appear to markedly influence muscle and bone atrophies; moreover, it made hypofunctioning of the thyroid more intense and, when combined with the growth hormone, masked the positive effect of the latter on the rats' bones.

  14. Proximal Neuropathy and Associated Skeletal Muscle Changes Resembling Denervation Atrophy in Hindlimbs of Chronic Hypoglycaemic Rats

    DEFF Research Database (Denmark)

    Jensen, Vivi F.H.; Molck, Anne Marie; Soeborg, Henrik

    2017-01-01

    Peripheral neuropathy is one of the most common complications of diabetic hyperglycaemia. Insulin-induced hypoglycaemia (IIH) might potentially exacerbate or contribute to neuropathy as hypoglycaemia also causes peripheral neuropathy. In rats, IIH induces neuropathy associated with skeletal muscle......, and severity of the myofibre atrophy correlated with severity of axonal degeneration in sciatic nerve. Both neuropathy and myopathy were still present after four weeks of recovery, although the neuropathy was less severe. In conclusion, the results suggest that peripheral neuropathy induced by IIH progresses...... changes. Aims of this study were to investigate the progression and sequence of histopathologic changes caused by chronic IIH in rat peripheral nerves and skeletal muscle, and whether such changes were reversible. Chronic IIH was induced by infusion of human insulin, followed by an infusion-free recovery...

  15. Proximal Neuropathy and Associated Skeletal Muscle Changes Resembling Denervation Atrophy in Hindlimbs of Chronic Hypoglycaemic Rats

    DEFF Research Database (Denmark)

    Jensen, Vivi F.H.; Molck, Anne Marie; Soeborg, Henrik

    2018-01-01

    Peripheral neuropathy is one of the most common complications of diabetic hyperglycaemia. Insulin-induced hypoglycaemia (IIH) might potentially exacerbate or contribute to neuropathy as hypoglycaemia also causes peripheral neuropathy. In rats, IIH induces neuropathy associated with skeletal muscle......, and severity of the myofibre atrophy correlated with severity of axonal degeneration in sciatic nerve. Both neuropathy and myopathy were still present after four weeks of recovery, although the neuropathy was less severe. In conclusion, the results suggest that peripheral neuropathy induced by IIH progresses...... changes. Aims of this study were to investigate the progression and sequence of histopathologic changes caused by chronic IIH in rat peripheral nerves and skeletal muscle, and whether such changes were reversible. Chronic IIH was induced by infusion of human insulin, followed by an infusion-free recovery...

  16. Genome-wide association study for claw disorders and trimming status in dairy cattle.

    Science.gov (United States)

    van der Spek, D; van Arendonk, J A M; Bovenhuis, H

    2015-02-01

    Performing a genome-wide association study (GWAS) might add to a better understanding of the development of claw disorders and the need for trimming. Therefore, the aim of the current study was to perform a GWAS on claw disorders and trimming status and to validate the results for claw disorders based on an independent data set. Data consisted of 20,474 cows with phenotypes for claw disorders and 50,238 cows with phenotypes for trimming status. Recorded claw disorders used in the current study were double sole (DS), interdigital hyperplasia (IH), sole hemorrhage (SH), sole ulcer (SU), white line separation (WLS), a combination of infectious claw disorders consisting of (inter-)digital dermatitis and heel erosion, and a combination of laminitis-related claw disorders (DS, SH, SU, and WLS). Of the cows with phenotypes for claw disorders, 1,771 cows were genotyped and these cow data were used for the GWAS on claw disorders. A SNP was considered significant when the false discovery rate≤0.05 and suggestive when the false discovery rate≤0.20. An independent data set of 185 genotyped bulls having at least 5 daughters with phenotypes (6,824 daughters in total) for claw disorders was used to validate significant and suggestive SNP detected based on the cow data. To analyze the trait "trimming status" (i.e., the need for claw trimming), a data set with 327 genotyped bulls having at least 5 daughters with phenotypes (18,525 daughters in total) was used. Based on the cow data, in total 10 significant and 45 suggestive SNP were detected for claw disorders. The 10 significant SNP were associated with SU, and mainly located on BTA8. The suggestive SNP were associated with DS, IH, SU, and laminitis-related claw disorders. Three of the suggestive SNP were validated in the data set of 185 bulls, and were located on BTA13, BTA14, and BTA17. For infectious claw disorders, SH, and WLS, no significant or suggestive SNP associations were detected. For trimming status, 1 significant

  17. Leiomodin-3-deficient mice display nemaline myopathy with fast-myofiber atrophy

    Directory of Open Access Journals (Sweden)

    Lei Tian

    2015-06-01

    Full Text Available Nemaline myopathy (NM is one of the most common forms of congenital myopathy, and affects either fast myofibers, slow myofibers, or both. However, an animal model for congenital myopathy with fast-myofiber-specific atrophy is not available. Furthermore, mutations in the leiomodin-3 (LMOD3 gene have recently been identified in a group of individuals with NM. However, it is not clear how loss of LMOD3 leads to NM. Here, we report a mouse mutant in which the piggyBac (PB transposon is inserted into the Lmod3 gene and disrupts its expression. Lmod3PB/PB mice show severe muscle weakness and postnatal growth retardation. Electron microscopy and immunofluorescence studies of the mutant skeletal muscles revealed the presence of nemaline bodies, a hallmark of NM, and disorganized sarcomeric structures. Interestingly, Lmod3 deficiency caused muscle atrophy specific to the fast fibers. Together, our results show that Lmod3 is required in the fast fibers for sarcomere integrity, and this study offers the first NM mouse model with muscle atrophy that is specific to fast fibers. This model could be a valuable resource for interrogating myopathy pathogenesis and developing therapeutics for NM as well as other pathophysiological conditions with preferential atrophy of fast fibers, including cancer cachexia and sarcopenia.

  18. The adipokine leptin increases skeletal muscle mass and significantly alters skeletal muscle miRNA expression profile in aged mice

    International Nuclear Information System (INIS)

    Hamrick, Mark W.; Herberg, Samuel; Arounleut, Phonepasong; He, Hong-Zhi; Shiver, Austin; Qi, Rui-Qun; Zhou, Li; Isales, Carlos M.

    2010-01-01

    Research highlights: → Aging is associated with muscle atrophy and loss of muscle mass, known as the sarcopenia of aging. → We demonstrate that age-related muscle atrophy is associated with marked changes in miRNA expression in muscle. → Treating aged mice with the adipokine leptin significantly increased muscle mass and the expression of miRNAs involved in muscle repair. → Recombinant leptin therapy may therefore be a novel approach for treating age-related muscle atrophy. -- Abstract: Age-associated loss of muscle mass, or sarcopenia, contributes directly to frailty and an increased risk of falls and fractures among the elderly. Aged mice and elderly adults both show decreased muscle mass as well as relatively low levels of the fat-derived hormone leptin. Here we demonstrate that loss of muscle mass and myofiber size with aging in mice is associated with significant changes in the expression of specific miRNAs. Aging altered the expression of 57 miRNAs in mouse skeletal muscle, and many of these miRNAs are now reported to be associated specifically with age-related muscle atrophy. These include miR-221, previously identified in studies of myogenesis and muscle development as playing a role in the proliferation and terminal differentiation of myogenic precursors. We also treated aged mice with recombinant leptin, to determine whether leptin therapy could improve muscle mass and alter the miRNA expression profile of aging skeletal muscle. Leptin treatment significantly increased hindlimb muscle mass and extensor digitorum longus fiber size in aged mice. Furthermore, the expression of 37 miRNAs was altered in muscles of leptin-treated mice. In particular, leptin treatment increased the expression of miR-31 and miR-223, miRNAs known to be elevated during muscle regeneration and repair. These findings suggest that aging in skeletal muscle is associated with marked changes in the expression of specific miRNAs, and that nutrient-related hormones such as leptin

  19. The adipokine leptin increases skeletal muscle mass and significantly alters skeletal muscle miRNA expression profile in aged mice

    Energy Technology Data Exchange (ETDEWEB)

    Hamrick, Mark W., E-mail: mhamrick@mail.mcg.edu [Department of Cellular Biology and Anatomy, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Department of Orthopaedic Surgery, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Herberg, Samuel; Arounleut, Phonepasong [Department of Cellular Biology and Anatomy, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Department of Orthopaedic Surgery, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); He, Hong-Zhi [Henry Ford Immunology Program, Henry Ford Health System, Detroit, MI (United States); Department of Dermatology, Henry Ford Health System, Detroit, MI (United States); Shiver, Austin [Department of Cellular Biology and Anatomy, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Department of Orthopaedic Surgery, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Qi, Rui-Qun [Henry Ford Immunology Program, Henry Ford Health System, Detroit, MI (United States); Department of Dermatology, Henry Ford Health System, Detroit, MI (United States); Zhou, Li [Henry Ford Immunology Program, Henry Ford Health System, Detroit, MI (United States); Department of Dermatology, Henry Ford Health System, Detroit, MI (United States); Department of Internal Medicine, Henry Ford Health System, Detroit, MI (United States); Isales, Carlos M. [Department of Cellular Biology and Anatomy, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Department of Orthopaedic Surgery, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); others, and

    2010-09-24

    Research highlights: {yields} Aging is associated with muscle atrophy and loss of muscle mass, known as the sarcopenia of aging. {yields} We demonstrate that age-related muscle atrophy is associated with marked changes in miRNA expression in muscle. {yields} Treating aged mice with the adipokine leptin significantly increased muscle mass and the expression of miRNAs involved in muscle repair. {yields} Recombinant leptin therapy may therefore be a novel approach for treating age-related muscle atrophy. -- Abstract: Age-associated loss of muscle mass, or sarcopenia, contributes directly to frailty and an increased risk of falls and fractures among the elderly. Aged mice and elderly adults both show decreased muscle mass as well as relatively low levels of the fat-derived hormone leptin. Here we demonstrate that loss of muscle mass and myofiber size with aging in mice is associated with significant changes in the expression of specific miRNAs. Aging altered the expression of 57 miRNAs in mouse skeletal muscle, and many of these miRNAs are now reported to be associated specifically with age-related muscle atrophy. These include miR-221, previously identified in studies of myogenesis and muscle development as playing a role in the proliferation and terminal differentiation of myogenic precursors. We also treated aged mice with recombinant leptin, to determine whether leptin therapy could improve muscle mass and alter the miRNA expression profile of aging skeletal muscle. Leptin treatment significantly increased hindlimb muscle mass and extensor digitorum longus fiber size in aged mice. Furthermore, the expression of 37 miRNAs was altered in muscles of leptin-treated mice. In particular, leptin treatment increased the expression of miR-31 and miR-223, miRNAs known to be elevated during muscle regeneration and repair. These findings suggest that aging in skeletal muscle is associated with marked changes in the expression of specific miRNAs, and that nutrient

  20. Effect of tamoxifen on fatty degeneration and atrophy of rotator cuff muscles in chronic rotator cuff tear: An animal model study.

    Science.gov (United States)

    Cho, Edward; Zhang, Yue; Pruznak, Anne; Kim, H Mike

    2015-12-01

    Fatty degeneration of the rotator cuff muscles is an irreversible change resulting from chronic rotator cuff tear and is associated with poor clinical outcomes following rotator cuff repair. We evaluated the effect of Tamoxifen, a competitive estrogen receptor inhibitor, on fatty degeneration using a mouse model for chronic rotator cuff tear. Sixteen adult mice were divided into two diet groups (Tamoxifen vs. Regular) and subjected to surgical creation of a large rotator cuff tear and suprascapular nerve transection in their left shoulder with the right shoulder serving as a control. The rotator cuff muscles were harvested at 16 weeks and subjected to histology and RT-PCR for adipogenic and myogenic markers. Histology showed substantially decreased atrophy and endomysial inflammation in Tamoxifen group, but no significant differences in the amount of intramuscular adipocytes and lipid droplets compared to the Regular group. With RT-PCR, the operated shoulders showed significant upregulation of myogenin and PPAR-γ, and downregulation of myostatin compared to the nonsurgical shoulder. No significant differences of gene expression were found between the two diet groups. Our study demonstrated that tamoxifen diet leads to decreased muscle atrophy and inflammatory changes following chronic rotator cuff tear, but has no apparent effect on adipogenesis. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  1. Muscle Atrophy Reversed by Growth Factor Activation of Satellite Cells in a Mouse Muscle Atrophy Model

    DEFF Research Database (Denmark)

    Hauerslev, Simon; Vissing, John; Krag, Thomas O

    2014-01-01

    mechanism that may contribute to the progressive muscle wasting seen in severely affected patients with muscular dystrophy and significant on-going regeneration. This treatment could potentially be applied to many conditions that feature muscle wasting to increase muscle bulk and strength.......Muscular dystrophies comprise a large group of inherited disorders that lead to progressive muscle wasting. We wanted to investigate if targeting satellite cells can enhance muscle regeneration and thus increase muscle mass. We treated mice with hepatocyte growth factor and leukemia inhibitory...... factor under three conditions: normoxia, hypoxia and during myostatin deficiency. We found that hepatocyte growth factor treatment led to activation of the Akt/mTOR/p70S6K protein synthesis pathway, up-regulation of the myognic transcription factors MyoD and myogenin, and subsequently the negative growth...

  2. Association of claw disorders with subclinical intramammary infections in Egyptian dairy cows

    Directory of Open Access Journals (Sweden)

    Walid Refaai

    2017-03-01

    Full Text Available Aim: Bovine mastitis and lameness are the most common production diseases affecting dairy farms worldwide resulting in huge economic impact and impaired animal welfare. The objective of this field study was to investigate the association of infectious and non-infectious claw disorders with the occurrence of subclinical intramammary infections (IMIs diagnosed by California mastitis test (CMT in dairy cows under Egyptian conditions. Materials and Methods: A total of 43 dairy cows were included in this field study. Subclinical IMI was diagnosed by CMT on all lactating quarters of cows. A cow was considered to have subclinical IMI if it had at least one subclinically infected quarter (=3. Cows were inspected carefully for claw disorders that recorded based on type and site. Locomotion and body condition scores were also recorded for each cow in addition to the limb affected. The association between the CMT and other explanatory variables was tested by Fisher's exact test. Results: The prevalence of infectious and non-infectious claw disorders was 81.4% (35/43 and 32.6% (14/43, respectively. Digital dermatitis (DD and heel horn erosion were the most prevalent infectious type with 79% (34/43 and 58% (25/43, respectively, while wall fissure was the most identified non-infectious one 11.6% (5/43. The prevalence of claw disorders in hind limbs was 88.4% (38/43 and 11.6% (5/43 in the forelimbs. Infectious claw disorders were significantly associated with the subclinical IMI diagnosed by CMT (p<0.05. Non-infectious claw affections, locomotion score, body condition score, and the affected limb had no association with the occurrence of subclinical IMI. Conclusion: DD is the highest prevalent claw disorder observed in dairy cows in Egypt. The hind limbs are more susceptible to claw disorders than the forelimbs. Infectious type of claw disorders is significantly associated with subclinical IMI diagnosed by CMT in dairy cows under Egyptian conditions indicating

  3. Spinal and bulbar muscular atrophy.

    Science.gov (United States)

    Lieberman, Andrew P

    2018-01-01

    Spinal and bulbar muscular atrophy (SBMA) is an adult-onset degenerative disorder of the neuromuscular system resulting in slowly progressive weakness and atrophy of the proximal limb and bulbar muscles. The disease is caused by the expansion of a CAG/glutamine tract in the amino-terminus of the androgen receptor. That SBMA exclusively affects males reflects the fact that critical pathogenic events are hormone-dependent. These include translocation of the polyglutamine androgen receptor from the cytoplasm to the nucleus and unfolding of the mutant protein. Studies of the pathology of SBMA subjects have revealed nuclear aggregates of the mutant androgen receptor, loss of lower motor neurons in the brainstem and spinal cord, and both neurogenic and myopathic changes in skeletal muscle. Mechanisms underlying disease pathogenesis include toxicity in both lower motor neurons and skeletal muscle, where effects on transcription, intracellular transport, and mitochondrial function have been documented. Therapies to treat SBMA patients remain largely supportive, although experimental approaches targeting androgen action or promoting degradation of the mutant androgen receptor protein or the encoding RNA are under active study. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. Congenital contractural arachnodactyly with neurogenic muscular atrophy: case report

    Directory of Open Access Journals (Sweden)

    Scola Rosana Herminia

    2001-01-01

    Full Text Available We report the case of a 3-1/2-year-old girl with hypotonia, multiple joint contractures, hip luxation, arachnodactyly, adducted thumbs, dolichostenomelia, and abnormal external ears suggesting the diagnosis of congenital contractural arachnodactyly (CCA. The serum muscle enzimes were normal and the needle electromyography showed active and chronic denervation. The muscle biopsy demonstrated active and chronic denervation compatible with spinal muscular atrophy. Analysis of exons 7 and 8 of survival motor neuron gene through polymerase chain reaction did not show deletions. Neurogenic muscular atrophy is a new abnormality associated with CCA, suggesting that CCA is clinically heterogeneous.

  5. Protein translation, proteolysis and autophagy in human skeletal muscle atrophy after spinal cord injury.

    Science.gov (United States)

    Lundell, L S; Savikj, M; Kostovski, E; Iversen, P O; Zierath, J R; Krook, A; Chibalin, A V; Widegren, U

    2018-02-08

    Spinal cord injury-induced loss of skeletal muscle mass does not progress linearly. In humans, peak muscle loss occurs during the first 6 weeks postinjury, and gradually continues thereafter. The aim of this study was to delineate the regulatory events underlying skeletal muscle atrophy during the first year following spinal cord injury. Key translational, autophagic and proteolytic proteins were analysed by immunoblotting of human vastus lateralis muscle obtained 1, 3 and 12 months following spinal cord injury. Age-matched able-bodied control subjects were also studied. Several downstream targets of Akt signalling decreased after spinal cord injury in skeletal muscle, without changes in resting Akt Ser 473 and Akt Thr 308 phosphorylation or total Akt protein. Abundance of mTOR protein and mTOR Ser 2448 phosphorylation, as well as FOXO1 Ser 256 phosphorylation and FOXO3 protein, decreased in response to spinal cord injury, coincident with attenuated protein abundance of E3 ubiquitin ligases, MuRF1 and MAFbx. S6 protein and Ser 235/236 phosphorylation, as well as 4E-BP1 Thr 37/46 phosphorylation, increased transiently after spinal cord injury, indicating higher levels of protein translation early after injury. Protein abundance of LC3-I and LC3-II decreased 3 months postinjury as compared with 1 month postinjury, but not compared to able-bodied control subjects, indicating lower levels of autophagy. Proteins regulating proteasomal degradation were stably increased in response to spinal cord injury. Together, these data provide indirect evidence suggesting that protein translation and autophagy transiently increase, while whole proteolysis remains stably higher in skeletal muscle within the first year after spinal cord injury. © 2018 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  6. Rapidly worsening bulbar symptoms in a patient with spinobulbar muscular atrophy

    Directory of Open Access Journals (Sweden)

    Montserrat Diaz-Abad

    2013-12-01

    Full Text Available X-linked spinobulbar muscular atrophy (Kennedy’s disease affects muscles and motor neurons, manifesting as weakness and wasting of bulbar, facial, and proximal limb muscles due to loss of anterior horn cells in the brain and spinal cord. We present the case of a patient with X-linked spinobulbar muscular atrophy with rapidly worsening bulbar symptoms caused by laryngopharyngeal irritation associated with a viral upper respiratory tract infection, seasonal allergies and laryngopharyngeal reflux, who dramatically improved with multimodality therapy.

  7. The effects of Capn1 gene inactivation on skeletal muscle growth, development, and atrophy, and the compensatory role of other proteolytic systems.

    Science.gov (United States)

    Kemp, C M; Oliver, W T; Wheeler, T L; Chishti, A H; Koohmaraie, M

    2013-07-01

    Myofibrillar protein turnover is a key component of muscle growth and degeneration, requiring proteolytic enzymes to degrade the skeletal muscle proteins. The objective of this study was to investigate the role of the calpain proteolytic system in muscle growth development using μ-calpain knockout (KO) mice in comparison with control wild-type (WT) mice, and evaluate the subsequent effects of silencing this gene on other proteolytic systems. No differences in muscle development between genotypes were observed during the early stages of growth due to the up regulation of other proteolytic systems. The KO mice showed significantly greater m-calpain protein abundance (P proteolytic systems to ensure muscle protein homeostasis in vivo. Furthermore, these data contribute to the existing evidence of the importance of the calpain system's involvement in muscle growth, development, and atrophy. Collectively, these data suggest that there are opportunities to target the calpain system to promote the growth and/or restoration of skeletal muscle mass.

  8. Unique fatality due to claw injuries in a tiger attack: a case report.

    Science.gov (United States)

    Pathak, Hrishikesh; Dixit, Pradeep; Dhawane, Shailendra; Meshram, Satin; Shrigiriwar, Manish; Dingre, Niraj

    2014-11-01

    This paper describes a unique case of a fatal tiger attack in the wild. In the present case, a tiger fatally mauled a 34-year-old female with its claws, instead of the usual mechanism of killing by the bite injury to the neck. The autopsy revealed multiple fatal and non-fatal injuries caused by the tiger claws. The characteristic injuries due to the tooth impacts were absent as the teeth of the offending tiger were either fallen or non-functional. To the best of our knowledge, probably this rare case would be the first reported human fatality due to the tiger claw injuries in the world. The purpose of the present article is to highlight the fatal injuries due to the tiger claws, as the claw-induced fatal injuries in a tiger attack are not reported in the medico-legal literature. Moreover, this report would be an illustrative one for differentiation between the fatal injuries due to the claws and tooth impacts in a tiger attack. Furthermore, the present report establishes the importance of the tiger claws as a source of fatal injuries in a tiger attack. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  9. Denervation atrophy is independent from Akt and mTOR activation and is not rescued by myostatin inhibition

    Directory of Open Access Journals (Sweden)

    Elizabeth M. MacDonald

    2014-04-01

    Full Text Available The purpose of our study was to compare two acquired muscle atrophies and the use of myostatin inhibition for their treatment. Myostatin naturally inhibits skeletal muscle growth by binding to ActRIIB, a receptor on the cell surface of myofibers. Because blocking myostatin in an adult wild-type mouse induces profound muscle hypertrophy, we applied a soluble ActRIIB receptor to models of disuse (limb immobilization and denervation (sciatic nerve resection atrophy. We found that treatment of immobilized mice with ActRIIB prevented the loss of muscle mass observed in placebo-treated mice. Our results suggest that this protection from disuse atrophy is regulated by serum and glucocorticoid-induced kinase (SGK rather than by Akt. Denervation atrophy, however, was not protected by ActRIIB treatment, yet resulted in an upregulation of the pro-growth factors Akt, SGK and components of the mTOR pathway. We then treated the denervated mice with the mTOR inhibitor rapamycin and found that, despite a reduction in mTOR activation, there is no alteration of the atrophy phenotype. Additionally, rapamycin prevented the denervation-induced upregulation of the mTORC2 substrates Akt and SGK. Thus, our studies show that denervation atrophy is not only independent from Akt, SGK and mTOR activation but also has a different underlying pathophysiological mechanism than disuse atrophy.

  10. Lack of caspase-3 attenuates immobilization-induced muscle atrophy and loss of tension generation along with mitigation of apoptosis and inflammation

    Science.gov (United States)

    Zhu, Shimei; Nagashima, Michio; Khan, Mahammad A.S; Yasuhara, Shingo; Kaneki, Masao; Jeevendra Martyn, J. A.

    2012-01-01

    Introduction Immobilization by casting induces disuse muscle atrophy (DMA). Methods Using wild type (WT) and caspase-3 knockout (KO) mice, we evaluated the effect of caspase-3 on muscle mass, apoptosis and inflammation during DMA. Results Caspase-3 deficiency significantly attenuated muscle mass decrease [gastrocnemius: 28 ± 1% in KO vs. 41 ± 3% in WT; soleus: 47 ± 2% in KO vs. 56 ± 2% in WT; (P immobilized versus contralateral hindlimb. Lack of caspase-3 decreased immobilization-induced increased apoptotic myonuclei (3.2-fold) and macrophage infiltration (2.2-fold) in soleus muscle and attenuated increased monocyte chemoattractant protein-1 mRNA expression (2-fold in KO vs. 18-fold in WT) in gastrocnemius. Conclusion Caspase-3 plays a key role in DMA and associated decreased tension, presumably by acting on the apoptosis and inflammation pathways. PMID:23401051

  11. Genome-wide association study for claw disorders and trimming status in dairy cattle

    NARCIS (Netherlands)

    Spek, van der D.; Arendonk, van J.A.M.; Bovenhuis, H.

    2015-01-01

    Performing a genome-wide association study (GWAS) might add to a better understanding of the development of claw disorders and the need for trimming. Therefore, the aim of the current study was to perform a GWAS on claw disorders and trimming status and to validate the results for claw disorders

  12. PetClaw: A scalable parallel nonlinear wave propagation solver for Python

    KAUST Repository

    Alghamdi, Amal; Ahmadia, Aron; Ketcheson, David I.; Knepley, Matthew; Mandli, Kyle; Dalcin, Lisandro

    2011-01-01

    We present PetClaw, a scalable distributed-memory solver for time-dependent nonlinear wave propagation. PetClaw unifies two well-known scientific computing packages, Clawpack and PETSc, using Python interfaces into both. We rely on Clawpack to provide the infrastructure and kernels for time-dependent nonlinear wave propagation. Similarly, we rely on PETSc to manage distributed data arrays and the communication between them.We describe both the implementation and performance of PetClaw as well as our challenges and accomplishments in scaling a Python-based code to tens of thousands of cores on the BlueGene/P architecture. The capabilities of PetClaw are demonstrated through application to a novel problem involving elastic waves in a heterogeneous medium. Very finely resolved simulations are used to demonstrate the suppression of shock formation in this system.

  13. From physical inactivity to immobilization: Dissecting the role of oxidative stress in skeletal muscle insulin resistance and atrophy.

    Science.gov (United States)

    Pierre, Nicolas; Appriou, Zephyra; Gratas-Delamarche, Arlette; Derbré, Frédéric

    2016-09-01

    In the literature, the terms physical inactivity and immobilization are largely used as synonyms. The present review emphasizes the need to establish a clear distinction between these two situations. Physical inactivity is a behavior characterized by a lack of physical activity, whereas immobilization is a deprivation of movement for medical purpose. In agreement with these definitions, appropriate models exist to study either physical inactivity or immobilization, leading thereby to distinct conclusions. In this review, we examine the involvement of oxidative stress in skeletal muscle insulin resistance and atrophy induced by, respectively, physical inactivity and immobilization. A large body of evidence demonstrates that immobilization-induced atrophy depends on the chronic overproduction of reactive oxygen and nitrogen species (RONS). On the other hand, the involvement of RONS in physical inactivity-induced insulin resistance has not been investigated. This observation outlines the need to elucidate the mechanism by which physical inactivity promotes insulin resistance. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Models for genetic evaluations of claw health traits in Spanish dairy cattle.

    Science.gov (United States)

    Pérez-Cabal, M A; Charfeddine, N

    2015-11-01

    Genetic parameters of 7 claw health traits from Spanish dairy cattle were estimated and the predictive ability of linear and ordinal threshold models were compared and assessed. This study included data on interdigital and digital dermatitis (DE), sole ulcer (SU), white line disease (WL), interdigital hyperplasia (IH), interdigital phlegmon (IP), and chronic laminitis (CL) collected between July 2012 and June 2013 from 834 dairy herds visited by 21 trained trimmers. An overall claw disorder (OCD) was also considered an indicator the absence or the presence of at least 1 of the 6 disorders. Claw health traits were scored as categorical traits with 3 degrees of severity (nonaffected, mild, and severe disorder). Genetic parameters were estimated by fitting both a standard linear model and an ordinal threshold animal model. Around 21% of cows had at least 1 claw disorder, and the most frequent disorders were SU, DE, WL, and CL. Heritabilities of claw disorders estimated with a linear model ranged from 0.01 (IP) to 0.05 (OCD), whereas estimates from the ordinal threshold models ranged from 0.06 to 0.39 (for IP and IH, respectively). Repeatabilities of claw health estimated with the linear model varied from 0.03 to 0.18 and estimates with the ordinal threshold model ranged from 0.33 to 0.69. The global trait OCD was correlated with all disorders, except for IH and IP when the linear model was fitted. Two different genetic backgrounds of claw disorders were found. Digital dermatitis showed positive correlations with IH and IP, whereas SU was positively correlated with WL and CL. The predictive ability of the models was assessed using mean squared error and Pearson correlation between the real observation and the corresponding prediction using cross-validation. Regardless of the claw health status, the linear model led to smaller mean squared error. However, differences in predictive ability were found when predicting nonaffected and affected animals. For most traits

  15. Aphakia correction with retropupillary fixated iris-claw lens (Artisan – long-term results

    Directory of Open Access Journals (Sweden)

    Schallenberg M

    2013-12-01

    Full Text Available Maurice Schallenberg,1,2 Dirk Dekowski,1 Angela Hahn,1 Thomas Laube,1,3 Klaus-Peter Steuhl,1 Daniel Meller11Department of Ophthalmology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany; 2HELIOS Klinikum Wuppertal, Wuppertal, Germany; 3Zentrum für Augenheilkunde PD Dr Laube, Düsseldorf, GermanyPurpose: To evaluate the technique, safety, and efficacy of the retropupillary implantation of iris-claw intraocular lenses in a long-term follow-up study.Patients and methods: This retrospective study included 31 eyes of 31 patients who underwent an Artisan aphakic intraocular lens implantation between January 2006 and February 2011 at the University Hospital Essen, Essen, Germany and at the Zentrum für Augenheilkunde PD Dr Laube, Düsseldorf, Germany. Preoperative data collected included demographics, etiology of aphakia, previous surgeries, preoperative eye pathology, intraocular pressure, clinical signs of endothelial cell loss, and best corrected visual acuity. Operative data and postoperative outcomes included the best corrected visual acuity, lens position, intraocular pressure, pigment dispersion, clinical signs of endothelial cell loss, development of macular edema, and other complications.Results: Thirty-one patients were included. The mean follow-up was 25.2 months (range: 4–48 months. The mean best corrected visual acuity postoperatively was 0.64 logarithm of the minimum angle of resolution (logMAR and varied from 0 logMAR to 3 logMAR. Some patients had a low visual acuity preoperatively because of preoperative eye pathologies. In 22 patients the visual acuity improved, in two patients the visual acuity remained unchanged, and seven patients showed a decreased visual acuity. Complications were peaked pupils (n=10 and retinal detachment in one case. Four patients showed an iris atrophy and high intraocular pressure was observed only in one patient. Subluxation of the intraocular lens, endothelial cell loss, and

  16. β-Hydroxy-β-methylbutyrate (HMB) prevents dexamethasone-induced myotube atrophy.

    Science.gov (United States)

    Aversa, Zaira; Alamdari, Nima; Castillero, Estibaliz; Muscaritoli, Maurizio; Rossi Fanelli, Filippo; Hasselgren, Per-Olof

    2012-07-13

    High levels of glucocorticoids result in muscle wasting and weakness. β-hydroxy-β-methylbutyrate (HMB) attenuates the loss of muscle mass in various catabolic conditions but the influence of HMB on glucocorticoid-induced muscle atrophy is not known. We tested the hypothesis that HMB prevents dexamethasone-induced atrophy in cultured myotubes. Treatment of cultured L6 myotubes with dexamethasone resulted in increased protein degradation and expression of atrogin-1 and MuRF1, decreased protein synthesis and reduced myotube size. All of these effects of dexamethasone were attenuated by HMB. Additional experiments provided evidence that the inhibitory effects of HMB on dexamethasone-induced increase in protein degradation and decrease in protein synthesis were regulated by p38/MAPK- and PI3K/Akt-dependent cell signaling, respectively. The present results suggest that glucocorticoid-induced muscle wasting can be prevented by HMB. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. Use of thermography to monitor sole haemorrhages and temperature distribution over the claws of dairy cattle.

    Science.gov (United States)

    Wilhelm, K; Wilhelm, J; Fürll, M

    2015-02-07

    Subclinical laminitis, an early pathological event in the development of many claw diseases, is an important factor in the welfare and economics of high-producing dairy cows. However, the aetiology and pathogenesis of this complex claw disease are not well understood. The present study investigated to what extent thermographic examination of claws is able to give information about corium inflammation, and whether the technique may be used as a diagnostic tool for early detection of subclinical laminitis. Moreover, the temperature distribution over the individual main claws was investigated to obtain further knowledge about pressure distribution on the claws. For this purpose the claws of 123 cows were evaluated in the first week after calving as well as after the second month of lactation for presence of sole haemorrhages (a sign of subclinical laminitis). Furthermore, the ground contact area was analysed by thermography. Sole haemorrhages were significantly increased by the second month of lactation. Thermography showed clear differences between the claws of the front limbs and hindlimbs, as well as between lateral and medial claws. Although the distribution of sole haemorrhages was consistent with the pattern of the temperature distribution over the main claws, no clear correlation was found between the claw temperature after calving and the visible laminitis-like changes (sole haemorrhages) eight weeks later. British Veterinary Association.

  18. Specific Characteristics of Injuries Inflicted by Claw Hammer.

    Science.gov (United States)

    Buchaillet, Céline; Gaudin, Arnaud; Rougé-Maillart, Clotilde; Jousset, Nathalie

    2016-09-01

    Claw hammers have the specific characteristic of having two distinct ends: one a flat head of variable form, the other bifurcated. So the use of this tool as a blunt instrument will cause varying injuries. The authors present two clinical cases of assault with a claw hammer. Examinations revealed two types of wound. A first injury composed of integumentary lacerations and underlying bone injuries in terms of "shape" suggested the use of a blunt instrument. A second injury made up of damage showing two parallel wounds or two wounds located one in the extension of the other suggested the use of an object with a bifurcated end. The combination of both types of injury should alert examiners to the possibility of the use of a claw hammer in causing the injuries in order to help direct investigators in their investigations and in the search for the weapon used. © 2016 American Academy of Forensic Sciences.

  19. Transcriptional activator TAp63 is upregulated in muscular atrophy during ALS and induces the pro-atrophic ubiquitin ligase Trim63

    Science.gov (United States)

    von Grabowiecki, Yannick; Abreu, Paula; Blanchard, Orphee; Palamiuc, Lavinia; Benosman, Samir; Mériaux, Sophie; Devignot, Véronique; Gross, Isabelle; Mellitzer, Georg; Gonzalez de Aguilar, José L; Gaiddon, Christian

    2016-01-01

    Mechanisms of muscle atrophy are complex and their understanding might help finding therapeutic solutions for pathologies such as amyotrophic lateral sclerosis (ALS). We meta-analyzed transcriptomic experiments of muscles of ALS patients and mouse models, uncovering a p53 deregulation as common denominator. We then characterized the induction of several p53 family members (p53, p63, p73) and a correlation between the levels of p53 family target genes and the severity of muscle atrophy in ALS patients and mice. In particular, we observed increased p63 protein levels in the fibers of atrophic muscles via denervation-dependent and -independent mechanisms. At a functional level, we demonstrated that TAp63 and p53 transactivate the promoter and increased the expression of Trim63 (MuRF1), an effector of muscle atrophy. Altogether, these results suggest a novel function for p63 as a contributor to muscular atrophic processes via the regulation of multiple genes, including the muscle atrophy gene Trim63. DOI: http://dx.doi.org/10.7554/eLife.10528.001 PMID:26919175

  20. Definitions of hammer toe and claw toe: an evaluation of the literature.

    Science.gov (United States)

    Schrier, Joost C M; Verheyen, Cees C P M; Louwerens, Jan Willem

    2009-01-01

    Lesser toe surgery is among the most conducted interventions in general orthopedic practice. However, the definitions of hammer toe and claw toe are not uniform. The objective of this literature study is to propose clear definitions for these deformities to establish unambiguous communication. A literature search was performed in the PubMed database (May 2006). Of 81 eligible articles, 42 that stated a clear definition of hammer toe or claw toe were selected. In all 35 articles in which hammer toe was clearly defined, flexion in the proximal interphalangeal joint was part of the definition. Seventeen articles (49%) defined hammer toe as a combination of metatarsophalangeal extension and proximal interphalangeal flexion. Thirteen articles showed flexion of the proximal interphalangeal joint as the single criterion. Twenty-three articles with a clear definition of claw toe were selected. Twenty-one articles (91%) showed metatarsophalangeal extension as part of the claw toe deformity. Twelve articles (52%) regarded metatarsophalangeal extension and flexion of the proximal interphalangeal and distal interphalangeal joints as the essential characteristics. Seven articles described a claw toe as metatarsophalangeal extension with flexion in the proximal interphalangeal joint. There are variations in the definitions of lesser toe deformities in the literature. We propose that extension of the metatarsophalangeal joint is the discriminating factor and essential characteristic for claw toe. Claw toe and hammer toe should be characterized by flexion in the proximal interphalangeal joint, which is the single criterion for a hammer toe. The flexibility of these joints could be a basic factor in discriminating between these deformities. The development of these deformities should be regarded as a continuum in the same pathophysiologic process.

  1. Low-intensity aerobic exercise training: inhibition of skeletal muscle atrophy in high-fat-diet-induced ovariectomized rats.

    Science.gov (United States)

    Kim, Hye Jin; Lee, Won Jun

    2017-09-30

    Postmenopausal women are highly susceptible to diseases, such as obesity, type 2 diabetes, osteoporosis, or skeletal muscle atrophy and many people recognize the need for regular physical activity. Aerobic exercise training is known to improve the oxidative capacity and insulin sensitivity of skeletal muscles. This study aimed to investigate the role of low-intensity aerobic exercise training on skeletal muscle protein degradation or synthesis in the plantaris muscles of high-fat-fed ovariectomized rats. Ovariectomized female rats were divided into two groups: a high-fat diet-sedentary group (HFD), and a high-fat diet-aerobic exercise group (HFD+EX). The exercise group exercised aerobically on a treadmill 5 days/week for 8 weeks. The rats progressively ran 30 min/day at 15 m/min, up to 40 min/day at 18 m/min, 0% slope, in the last 4 weeks. Although aerobic exercise led to significantly increased AMP-activated protein kinase (AMPK) phosphorylation at Thr172, phosphorylation of the mammalian target of rapamycin (mTOR) substrate Thr389 S6K1 level did not decrease. Additionally, even though Akt activity did not increase at Ser473, the atrogin-1 level significantly decreased in the exercise group compared to the non-exercise group. Immunohistochemical staining revealed that high-fat-induced TSC2 protein expression was eliminated in response to aerobic exercise. These results suggest that aerobic exercise can inhibit skeletal muscle protein degradation, but it cannot increase protein synthesis in the plantaris muscle of high-fat-fed ovariectomized rats. Our findings have implications in understanding skeletal muscle mass maintenance with low intensity aerobic exercise in post-menopausal women. ©2017 The Korean Society for Exercise Nutrition

  2. Computed tomographic findings of skeletal muscles in amyotrophic lateral sclerosis (ALS)

    International Nuclear Information System (INIS)

    Takahashi, Ryosuke; Imai, Terukuni; Sadashima, Hiromichi; Matsumoto, Sadayuki; Yamamoto, Toru; Kusaka, Hirobumi; Yamasaki, Masahiro; Maya, Kiyomi; Tanabe, Masaya

    1989-01-01

    We evaluated the Computed Tomographic (CT) findings of skeletal muscles in 12 cases of amyotrophic lateral sclerosis (ALS), 1 case of spinal progressive muscular atrophy (SPMA), and 1 case of Kugelberg-Welander disease. CT examination was performed in the neck, shoulders, abdomen, pelvis, thighs, and lower legs, 15 muscles were selected for evaluation. The following muscles tended to be affected: m. transversospinalis (12 cases were abnormal), m. deltoideus (10), m. subscapularis (10), m. infraspinatus (10), mm. dorsi (12), hamstring muscles (14), m. tibialis anterior (14), and m. triceps surae (14). On the contrary, the following muscles tended to be preserved: m. sternocleidomastoideus (only 7 cases were abnormal), m. psoas major (7), m. gluteus maximus (7), m. rectus femoris (7), m. sartorius (7) and m. gracilis (6). The distribution of the muscles affected showed neither proximal nor distal dominancy. As the disease advanced, however, all the muscles became affected without any severity. CT findings of skeletal muscles in ALS were characterized by muscle atrophy and fat infiltration, which showed a patchy, linear, or moth-eaten appearance. In mildly affected cases, there was muscle atrophy without internal architectual changes. In moderately affected cases, muscle atrophy advanced and internal architectural changes (patchy, linear, and moth-eaten fat infiltration) became evident. In most advanced cases, every muscle showed a ragged appearance because of severe muscle atrophy and internal architectural changes. These findings were well distinguished from those of SPMA, which resembled the CT pattern of primary muscle diseases. (author)

  3. Computed tomographic findings of skeletal muscles in amyotrophic lateral sclerosis (ALS)

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, Ryosuke; Imai, Terukuni; Sadashima, Hiromichi; Matsumoto, Sadayuki; Yamamoto, Toru; Kusaka, Hirobumi; Yamasaki, Masahiro; Maya, Kiyomi; Tanabe, Masaya (Kitano Hospital, Osaka (Japan))

    1989-04-01

    We evaluated the Computed Tomographic (CT) findings of skeletal muscles in 12 cases of amyotrophic lateral sclerosis (ALS), 1 case of spinal progressive muscular atrophy (SPMA), and 1 case of Kugelberg-Welander disease. CT examination was performed in the neck, shoulders, abdomen, pelvis, thighs, and lower legs, 15 muscles were selected for evaluation. The following muscles tended to be affected: m. transversospinalis (12 cases were abnormal), m. deltoideus (10), m. subscapularis (10), m. infraspinatus (10), mm. dorsi (12), hamstring muscles (14), m. tibialis anterior (14), and m. triceps surae (14). On the contrary, the following muscles tended to be preserved: m. sternocleidomastoideus (only 7 cases were abnormal), m. psoas major (7), m. gluteus maximus (7), m. rectus femoris (7), m. sartorius (7) and m. gracilis (6). The distribution of the muscles affected showed neither proximal nor distal dominancy. As the disease advanced, however, all the muscles became affected without any severity. CT findings of skeletal muscles in ALS were characterized by muscle atrophy and fat infiltration, which showed a patchy, linear, or moth-eaten appearance. In mildly affected cases, there was muscle atrophy without internal architectual changes. In moderately affected cases, muscle atrophy advanced and internal architectural changes (patchy, linear, and moth-eaten fat infiltration) became evident. In most advanced cases, every muscle showed a ragged appearance because of severe muscle atrophy and internal architectural changes. These findings were well distinguished from those of SPMA, which resembled the CT pattern of primary muscle diseases. (author).

  4. How to diminish calcium loss and muscle atrophy in space

    Science.gov (United States)

    Gorgolewski, S.

    Humans in micro-gravity suffer from Ca loss and muscle atrophy, efforts are made to prevent it by means of physical exercises and with medicaments. The tread-mill and exercise bike are just two most frequently used examples. This can and should be widely extended, and in such a way as to mimic as close as possible the normal loading of the muscles and skeleton which we experience here on the earth. Special very light weight active harness is proposed which monitors the body loading. This is accomplished by means of computer aided monitoring of muscle and bone loading systems. Using feedback it helps the crew to load their bodies and skeletons in the same way as it happens here on the earth. The active exercise mat with pressure sensors first creates a record here on the earth of all normal muscle tensions during exercise. In space the computer guides each exercising crew member to follow their earthbound training routine. High care is needed to select the best and most effective exercises which should demand least energy, yet providing the very best results. May I suggest the very best known to me kind of comprehensive exercises: Yoga. Doing it on the Earth you need next to none special training equipment. Our body is in principle all we need here to do Yoga exercises on the Earth. Integral part of Yoga exercises are abdominal breathing exercises, which can slow down the breathing rate even threefold. This improves the oxygen and CO_2 exchange and massages all internal organs around the clock, helping the adept to stay fit and also keeps their minds steady and calm. Yoga exercises should be mastered already here on the earth, providing the crew with much greater tolerance to micro-gravity. In Yoga we acquire the tolerance not only to zero gravity but also to "negative" gravity: as it happens in all inverted positions. This should help the astronauts to be more tolerant of the half way only step into "zero gravity". Weightlessness state provides us the ultimate in

  5. Extraction of Glycosaminoglycans Containing Glucosamine and Chondroitin Sulfate from Chicken Claw Cartilage

    Directory of Open Access Journals (Sweden)

    Tri Dewanti Widyaningsih

    2017-12-01

    Full Text Available Chicken cartilage (claw is a waste of chicken cuts which are widely available in Indonesia. Cartilage part of chicken claw becomes a potential source of chondroitin sulfate (CS and glucosamine (GS. This study aims to determine the most optimal extraction methods of CS and GS from cartilage of chicken claw. Various types of extraction methods used in this study are taken from the extraction by using boiling water (2 and 2.5 hours, acetic acid (7 and 17 hours, as well as proteolysis by papain (24 and 48 hours. Parameters observed include chemical characteristics of powdered cartilage of chicken claw as well as CS and GS levels in powdered cartilage of chicken claw extract. The results of this research show that the levels of CS and GS of chicken claw cartilage powder were 2.17% and 13%. Meanwhile, the highest GS level was obtained from the extraction with water treatment for 2.5 hours which was 8.1%. The treatment and duration of extraction will significantly affect the number of GS which was produced. The highest content of CS was obtained from the extraction with the enzyme treatment for 48 hours which was 2.47%. The best treatment is the extraction with water treatment for 2.5 hours which were the extracts with GS levels of 8.1% and 2.03% CS was selected through the analysis of multiple attribute.

  6. Sensory nerve cross-anastomosis and electrical muscle stimulation synergistically enhance functional recovery of chronically denervated muscle.

    Science.gov (United States)

    Willand, Michael P; Holmes, Michael; Bain, James R; de Bruin, Hubert; Fahnestock, Margaret

    2014-11-01

    Long-term muscle denervation leads to severe and irreversible atrophy coupled with loss of force and motor function. These factors contribute to poor functional recovery following delayed reinnervation. The authors' previous work demonstrated that temporarily suturing a sensory nerve to the distal motor stump (called sensory protection) significantly reduces muscle atrophy and improves function following reinnervation. The authors have also shown that 1 month of electrical stimulation of denervated muscle significantly improves function and reduces atrophy. In this study, the authors tested whether a combination of sensory protection and electrical stimulation would enhance functional recovery more than either treatment alone. Rat gastrocnemius muscles were denervated by cutting the tibial nerve. The peroneal nerve was then sutured to the distal tibial stump following 3 months of treatment (i.e., electrical stimulation, sensory protection, or both). Three months after peroneal repair, functional and histologic measurements were taken. All treatment groups had significantly higher muscle weight (pstimulation or sensory protection alone. The combined treatment also produced motor unit counts significantly greater than sensory protection alone (p<0.05). The combination treatment synergistically reduces atrophy and improves reinnervation and functional measures following delayed nerve repair, suggesting that these approaches work through different mechanisms. The authors' research supports the clinical use of both modalities together following peripheral nerve injury.

  7. Perspectives on the treatment of claw lesions in cattle

    Directory of Open Access Journals (Sweden)

    Shearer JK

    2015-06-01

    Full Text Available Jan K Shearer,1 Paul J Plummer,1,2 Jennifer A Schleining11Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA, USA; 2Veterinary Microbiology and Preventive Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA, USAAbstract: Lameness is a leading cause of welfare and culling issues in cattle, with claw lesions accounting for the majority of these issues. Although the treatment of claw lesions in cattle is a daily activity for hoof trimmers, veterinarians, and livestock producers, there is surprisingly little information in the peer-reviewed literature on which to base strong evidence-based conclusions. As a consequence, many treatment modalities used are empirical and, in some cases, may be counterproductive to rapid lesion healing. Furthermore, many of these empirical treatment modalities fail to fully consider the underlying pathogenesis of the disease process and the implications that it has on lesion healing. For example, sole ulcers are largely a consequence of metabolic disorders and mechanical overloading. Therapeutic interventions that fail to address the weight-bearing issues are unlikely to be successful. Likewise, white line disease is believed to be predisposed by rumen acidosis and laminitis, and interventions need to include in them appropriate measures to prevent further cases through nutritional management. The goal of this review paper is to review the pathogenesis of claw lesions in the context of the published literature and allow the reader to arrive at rational treatment interventions based on the best available information. The use of an orthopedic block applied to the healthy claw of a lame foot, judicious use of bandage or wrap, careful selection of parenteral or topical therapy, and a treatment protocol to manage pain and promote recovery are key components of responsible management of lameness disorders in cattle.Keywords: lameness

  8. HDAC4 preserves skeletal muscle structure following long-term denervation by mediating distinct cellular responses.

    Science.gov (United States)

    Pigna, Eva; Renzini, Alessandra; Greco, Emanuela; Simonazzi, Elena; Fulle, Stefania; Mancinelli, Rosa; Moresi, Viviana; Adamo, Sergio

    2018-02-24

    Denervation triggers numerous molecular responses in skeletal muscle, including the activation of catabolic pathways and oxidative stress, leading to progressive muscle atrophy. Histone deacetylase 4 (HDAC4) mediates skeletal muscle response to denervation, suggesting the use of HDAC inhibitors as a therapeutic approach to neurogenic muscle atrophy. However, the effects of HDAC4 inhibition in skeletal muscle in response to long-term denervation have not been described yet. To further study HDAC4 functions in response to denervation, we analyzed mutant mice in which HDAC4 is specifically deleted in skeletal muscle. After an initial phase of resistance to neurogenic muscle atrophy, skeletal muscle with a deletion of HDAC4 lost structural integrity after 4 weeks of denervation. Deletion of HDAC4 impaired the activation of the ubiquitin-proteasome system, delayed the autophagic response, and dampened the OS response in skeletal muscle. Inhibition of the ubiquitin-proteasome system or the autophagic response, if on the one hand, conferred resistance to neurogenic muscle atrophy; on the other hand, induced loss of muscle integrity and inflammation in mice lacking HDAC4 in skeletal muscle. Moreover, treatment with the antioxidant drug Trolox prevented loss of muscle integrity and inflammation in in mice lacking HDAC4 in skeletal muscle, despite the resistance to neurogenic muscle atrophy. These results reveal new functions of HDAC4 in mediating skeletal muscle response to denervation and lead us to propose the combined use of HDAC inhibitors and antioxidant drugs to treat neurogenic muscle atrophy.

  9. Morphological correlates of the grooming claw in distal phalanges of platyrrhines and other primates: a preliminary study.

    Science.gov (United States)

    Maiolino, Stephanie; Boyer, Doug M; Rosenberger, Alfred

    2011-12-01

    Grooming claws are present on the second pedal digits of strepsirhines and on the second and third pedal digits of tarsiers. However, their presence in New World monkeys is often overlooked. As such, the absence of a grooming claw is generally considered an anthropoid synapomorphy. This study utilizes a quantitative multivariate analysis to define grooming claw morphology and document its presence in platyrrhine monkeys. Our results show that owl monkeys possess grooming claws similar to those of strepsirhines, while titi monkeys possess grooming claw-like morphology. Therefore, we conclude that anthropoids are not clearly united by the absence of a grooming claw. Furthermore, due to their presence in three major primate clades, we infer that it is likely that a grooming claw was present on the second pedal digit of the ancestor of living primates. Therefore, we advise the reassessment of fossil adapids in light of the anatomical correlates described here. This should increase resolution on the homology and polarity of grooming claw morphology, and, therefore, will help provide a sharper picture of primate evolution. Copyright © 2011 Wiley Periodicals, Inc.

  10. Pedal claw curvature in birds, lizards and mesozoic dinosaurs--complicated categories and compensating for mass-specific and phylogenetic control.

    Directory of Open Access Journals (Sweden)

    Aleksandra V Birn-Jeffery

    Full Text Available Pedal claw geometry can be used to predict behaviour in extant tetrapods and has frequently been used as an indicator of lifestyle and ecology in Mesozoic birds and other fossil reptiles, sometimes without acknowledgement of the caveat that data from other aspects of morphology and proportions also need to be considered. Variation in styles of measurement (both inner and outer claw curvature angles has made it difficult to compare results across studies, as have over-simplified ecological categories. We sought to increase sample size in a new analysis devised to test claw geometry against ecological niche. We found that taxa from different behavioural categories overlapped extensively in claw geometry. Whilst most taxa plotted as predicted, some fossil taxa were recovered in unexpected positions. Inner and outer claw curvatures were statistically correlated, and both correlated with relative claw robusticity (mid-point claw height. We corrected for mass and phylogeny, as both likely influence claw morphology. We conclude that there is no strong mass-specific effect on claw curvature; furthermore, correlations between claw geometry and behaviour are consistent across disparate clades. By using independent contrasts to correct for phylogeny, we found little significant relationship between claw geometry and behaviour. 'Ground-dweller' claws are less curved and relatively dorsoventrally deep relative to those of other behavioural categories; beyond this it is difficult to assign an explicit category to a claw based purely on geometry.

  11. The Inhibitory Core of the Myostatin Prodomain: Its Interaction with Both Type I and II Membrane Receptors, and Potential to Treat Muscle Atrophy.

    Science.gov (United States)

    Ohsawa, Yutaka; Takayama, Kentaro; Nishimatsu, Shin-ichiro; Okada, Tadashi; Fujino, Masahiro; Fukai, Yuta; Murakami, Tatsufumi; Hagiwara, Hiroki; Itoh, Fumiko; Tsuchida, Kunihiro; Hayashi, Yoshio; Sunada, Yoshihide

    2015-01-01

    Myostatin, a muscle-specific transforming growth factor-β (TGF-β), negatively regulates skeletal muscle mass. The N-terminal prodomain of myostatin noncovalently binds to and suppresses the C-terminal mature domain (ligand) as an inactive circulating complex. However, which region of the myostatin prodomain is required to inhibit the biological activity of myostatin has remained unknown. We identified a 29-amino acid region that inhibited myostatin-induced transcriptional activity by 79% compared with the full-length prodomain. This inhibitory core resides near the N-terminus of the prodomain and includes an α-helix that is evolutionarily conserved among other TGF-β family members, but suppresses activation of myostatin and growth and differentiation factor 11 (GDF11) that share identical membrane receptors. Interestingly, the inhibitory core co-localized and co-immunoprecipitated with not only the ligand, but also its type I and type II membrane receptors. Deletion of the inhibitory core in the full-length prodomain removed all capacity for suppression of myostatin. A synthetic peptide corresponding to the inhibitory core (p29) ameliorates impaired myoblast differentiation induced by myostatin and GDF11, but not activin or TGF-β1. Moreover, intramuscular injection of p29 alleviated muscle atrophy and decreased the absolute force in caveolin 3-deficient limb-girdle muscular dystrophy 1C model mice. The injection suppressed activation of myostatin signaling and restored the decreased numbers of muscle precursor cells caused by caveolin 3 deficiency. Our findings indicate a novel concept for this newly identified inhibitory core of the prodomain of myostatin: that it not only suppresses the ligand, but also prevents two distinct membrane receptors from binding to the ligand. This study provides a strong rationale for the use of p29 in the amelioration of skeletal muscle atrophy in various clinical settings.

  12. Muscles in a mouse model of spinal muscular atrophy show profound defects in neuromuscular development even in the absence of failure in neuromuscular transmission or loss of motor neurons

    OpenAIRE

    Lee, Young il; Mikesh, Michelle; Smith, Ian; Rimer, Mendell; Thompson, Wesley

    2011-01-01

    A mouse model of the devastating human disease "spinal muscular atrophy" (SMA) was used to investigate the severe muscle weakness and spasticity that precedes the death of these animals near the end of the 2nd postnatal week. Counts of motor units to the soleus muscle as well as of axons in the soleus muscle nerve showed no loss of motor neurons. Similarly, neither immunostaining of neuromuscular junctions nor the measurement of the tension generated by nerve stimulation gave evidence of any ...

  13. Pioneer identification of fake tiger claws using morphometric and DNA-based analysis in wildlife forensics in India.

    Science.gov (United States)

    Vipin; Sharma, Vinita; Sharma, Chandra Prakash; Kumar, Ved Prakash; Goyal, Surendra Prakash

    2016-09-01

    The illegal trade in wildlife is a serious threat to the existence of wild animals throughout the world. The short supply and high demand for wildlife articles have caused an influx of many different forms of fake wildlife articles into this trade. The task of identifying the materials used in making such articles poses challenges in wildlife forensics as different approaches are required for species identification. Claws constitute 3.8% of the illegal animal parts (n=2899) received at the Wildlife Institute of India (WII) for species identification. We describe the identification of seized suspected tiger claws (n=18) using a combined approach of morphometric and DNA-based analysis. The differential keratin density, determined using X-ray radiographs, indicated that none of the 18 claws were of any large cat but were fake. We determined three claw measurements, viz. ac (from the external coronary dermo-epidermal interface to the epidermis of the skin fold connecting the palmar flanges of the coronary horn), bc (from the claw tip to the epidermis of the skin fold connecting the palmar flanges of the coronary horn) and the ratio bc/ac, for all the seized (n=18), tiger (n=23) and leopard (n=49) claws. Univariate and multivariate statistical analyses were performed using SPSS. A scatter plot generated using canonical discriminant function analysis revealed that of the 18 seized claws, 14 claws formed a cluster separate from the clusters of the tiger and leopard claws, whereas the remaining four claws were within the leopard cluster. Because a discrepancy was observed between the X-ray images and the measurements of these four claws, one of the claw that clustered with the leopard claws was chosen randomly and DNA analysis carried out using the cyt b (137bp) and 16S rRNA (410bp) genes. A BLAST search and comparison with the reference database at WII indicated that the keratin material of the claw was derived from Bos taurus (cattle). This is a pioneering discovery, and

  14. Genetic parameters for claw disorders in Dutch dairy cattle and correlations with conformation traits.

    Science.gov (United States)

    van der Waaij, E H; Holzhauer, M; Ellen, E; Kamphuis, C; de Jong, G

    2005-10-01

    Impaired claw health is one of the major problems causing production loss and reduced animal welfare in dairy cattle. In response, the Dutch Animal Health Service (GD) Ltd. initiated this study, in which claws of lactating and near-term cows and heifers in 430 herds were trimmed by hoof trimmers and the health status of the rear claws recorded. Only herds with >75% of the animals having feet trimmed were considered, resulting in records on 21,611 animals. Eight claw disorders were scored: digital dermatitis (DD), interdigital dermatitis/heel horn erosions (IDHE), sole hemorrhage (SH), chronic laminitis (CL), sole ulcer (SU), white line disease (WLD), interdigital hyperplasia (HYP), and interdigital phlegmona (IP). The prevalence varied from 0.6% (IP) to 39.9% (SH). More than 70% of the animals had at least one claw disorder. Conformation traits and locomotion were recorded once during the animal's first lactation by trained classifiers of the Royal Dutch Cattle Syndicate and completely independent of the moment of claw trimming. Heritabilities were estimated using a sire model, and ranged from <0.01 (IP) to 0.10 (DD and HYP). Genetic correlations of incidences of claw disorders with locomotion were variable, ranging from 0.13 (SH) to -0.91 (CL). Genetic correlations with the rear leg conformation traits were lower, ranging from 0.04 (ID with rear leg side view) to -0.69 (IP with rear leg rear view).

  15. Development and evolution of the mammalian limb: adaptive diversification of nails, hooves, and claws.

    Science.gov (United States)

    Hamrick, M W

    2001-01-01

    Paleontological evidence indicates that the evolutionary diversification of mammals early in the Cenozoic era was characterized by an adaptive radiation of distal limb structures. Likewise, neontological data show that morphological variation in distal limb integumentary appendages (e.g., nails, hooves, and claws) can be observed not only among distantly related mammalian taxa but also among closely related species within the same clade. Comparative analysis of nail, claw, and hoof morphogenesis reveals relatively subtle differences in mesenchymal and epithelial patterning underlying these adult differences in distal limb appendage morphology. Furthermore, studies of regulatory gene expression during vertebrate claw development demonstrate that many of the signaling molecules involved in patterning ectodermal derivatives such as teeth, hair, and feathers are also involved in organizing mammalian distal limb appendages. For example, Bmp4 signaling plays an important role during the recruitment of mesenchymal cells into the condensations forming the terminal phalanges, whereas Msx2 affects the length of nails and claws by suppressing proliferation of germinal epidermal cells. Evolutionary changes in the form of distal integumentary appendages may therefore result from changes in gene expression during formation of mesenchymal condensations (Bmp4, posterior Hox genes), induction of the claw fold and germinal matrix (shh), and/or proliferation of epidermal cells in the claw matrix (Msx1, Msx2). The prevalence of convergences and parallelisms in nail and claw structure among mammals underscores the existence of multiple morphogenetic pathways for evolutionary change in distal limb appendages.

  16. Development of Claw Traits and Claw Lesions in Dairy Cows kept on different floor systems

    NARCIS (Netherlands)

    Somers, J.G.C.J.; Schouten, W.G.P.; Frankena, K.; Noordhuizen-Stassen, E.N.; Metz, J.H.M.

    2005-01-01

    Several claw shape measurements, horn hardness, and horn growth and wear were recorded monthly at 12 dairy farms to investigate the effect of floor type and changes in these traits over time. Herds were either housed on a slatted floor (SL), solid concrete floor (SC), grooved floor (GR), or on a

  17. Myopathy in Childhood Muscle-Specific Kinase Myasthenia Gravis.

    Science.gov (United States)

    Kirzinger, Lukas; Khomenko, Andrei; Schulte-Mattler, Wilhelm; Backhaus, Roland; Platen, Sabine; Schalke, Berthold

    2016-12-01

    Adult and pediatric patients suffering from MuSK (muscle-specific kinase) -antibody positive myasthenia gravis exhibit similar features to individuals with acetylcholine receptor (AChR) antibodies, but they differ in several characteristics such as a predominant bulbar, respiratory and neck weakness, a generally worse disease severity and a tendency to develop muscle atrophy. Muscle atrophy is a rare phenomenon that is usually restricted to the facial muscles. We describe a girl with MuSK-antibody positive myasthenia gravis who developed a myopathy with severe generalized muscular weakness, muscle atrophy, and myopathic changes on electromyography. This is the first published example of a generalized myopathic syndrome in myasthenia gravis. We review the relevant literature and discuss the hypothesis of a mitochondrial myopathy as a pathogenic mechanism in MuSK-antibody positive myasthenia gravis. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. PyClaw: Accessible, Extensible, Scalable Tools for Wave Propagation Problems

    KAUST Repository

    Ketcheson, David I.; Mandli, Kyle; Ahmadia, Aron; Alghamdi, Amal; de Luna, Manuel Quezada; Parsani, Matteo; Knepley, Matthew G.; Emmett, Matthew

    2012-01-01

    Development of scientific software involves tradeoffs between ease of use, generality, and performance. We describe the design of a general hyperbolic PDE solver that can be operated with the convenience of MATLAB yet achieves efficiency near that of hand-coded Fortran and scales to the largest supercomputers. This is achieved by using Python for most of the code while employing automatically wrapped Fortran kernels for computationally intensive routines, and using Python bindings to interface with a parallel computing library and other numerical packages. The software described here is PyClaw, a Python-based structured grid solver for general systems of hyperbolic PDEs [K. T. Mandli et al., PyClaw Software, Version 1.0, http://numerics.kaust.edu.sa/pyclaw/ (2011)]. PyClaw provides a powerful and intuitive interface to the algorithms of the existing Fortran codes Clawpack and SharpClaw, simplifying code development and use while providing massive parallelism and scalable solvers via the PETSc library. The package is further augmented by use of PyWENO for generation of efficient high-order weighted essentially nonoscillatory reconstruction code. The simplicity, capability, and performance of this approach are demonstrated through application to example problems in shallow water flow, compressible flow, and elasticity.

  19. PyClaw: Accessible, Extensible, Scalable Tools for Wave Propagation Problems

    KAUST Repository

    Ketcheson, David I.

    2012-08-15

    Development of scientific software involves tradeoffs between ease of use, generality, and performance. We describe the design of a general hyperbolic PDE solver that can be operated with the convenience of MATLAB yet achieves efficiency near that of hand-coded Fortran and scales to the largest supercomputers. This is achieved by using Python for most of the code while employing automatically wrapped Fortran kernels for computationally intensive routines, and using Python bindings to interface with a parallel computing library and other numerical packages. The software described here is PyClaw, a Python-based structured grid solver for general systems of hyperbolic PDEs [K. T. Mandli et al., PyClaw Software, Version 1.0, http://numerics.kaust.edu.sa/pyclaw/ (2011)]. PyClaw provides a powerful and intuitive interface to the algorithms of the existing Fortran codes Clawpack and SharpClaw, simplifying code development and use while providing massive parallelism and scalable solvers via the PETSc library. The package is further augmented by use of PyWENO for generation of efficient high-order weighted essentially nonoscillatory reconstruction code. The simplicity, capability, and performance of this approach are demonstrated through application to example problems in shallow water flow, compressible flow, and elasticity.

  20. Claw-decompositions and Tutte-orientations

    DEFF Research Database (Denmark)

    Barat, Janos; Thomassen, Carsten

    2006-01-01

    We conjecture that, for each tree T there exists a natural number k(T) such that the following holds: If G is a k(T)-edge-connected graph such that \\E(T)\\ divides \\EG)\\, then the edges of G can be divided into parts, each of which is isomorphic to T. We prove that for T=K-1,K-3 (the claw), this h......We conjecture that, for each tree T there exists a natural number k(T) such that the following holds: If G is a k(T)-edge-connected graph such that \\E(T)\\ divides \\EG)\\, then the edges of G can be divided into parts, each of which is isomorphic to T. We prove that for T=K-1,K-3 (the claw......), this holds if and only if there exists a (smallest) natural number k(t) such that every k(t)-edge-connected graph has an orientation for which the indegree of each vertex equals its outdegree modulo 3. Tutte's 3-flow conjecture says that k(t)=4. We prove the weaker statement that every 4[ log n...

  1. Measuring Claw Conformation in Cattle: Assessing the Agreement between Manual and Digital Measurement

    Directory of Open Access Journals (Sweden)

    Linda J. Laven

    2015-08-01

    Full Text Available Five measurements of claw conformation (toe angle, claw height, claw width, toe length and abaxial groove length taken directly from the hoof were compared with the measurements taken from digital images of the same claws. Concordance correlation coefficients and limits-of-agreement analysis showed that, for four of the five measures (claw height, claw width, toe length and abaxial groove length, agreement was too poor for digital and manual measures to be used interchangeably. For all four of these measures, Liao’s modified concordance correlation coefficient (mCCC was ≤0.4, indicating poor concordance despite Pearson’s correlation being >0.6 in all cases. The worst concordance was seen for toe length (mCCC = 0.13. Limits-of-agreement analysis showed that, for all four measures, there was a large variation in the difference between the manual and digital methods, even when the effect of mean on difference was accounted for, with the 95% limits-of-agreement for the four measures being further away from the mean difference than 10% of the mean in all four cases. The only one of the five measures with an acceptable concordance between digital and manual measurement was toe angle (mCCC = 0.81. Nevertheless, the limits-of-agreement analysis showed that there was a systematic bias with, on average, the manual measure of toe angle, being 2.1° smaller than the digital. The 95% limits-of-agreement for toe angle were ±3.4°, probably at the upper limit of what is acceptable. However, the lack of data on the variability of individual measurements of claw conformation means that it is unclear how this variability compares to measurement of toe angle in the same animal using the same or a different manual technique.

  2. Boosted Regeneration and Reduced Denervated Muscle Atrophy by NeuroHeal in a Pre-clinical Model of Lumbar Root Avulsion with Delayed Reimplantation.

    Science.gov (United States)

    Romeo-Guitart, David; Forés, Joaquim; Navarro, Xavier; Casas, Caty

    2017-09-20

    The "gold standard" treatment of patients with spinal root injuries consists of delayed surgical reconnection of nerves. The sooner, the better, but problems such as injury-induced motor neuronal death and muscle atrophy due to long-term denervation mean that normal movement is not restored. Herein we describe a preclinical model of root avulsion with delayed reimplantation of lumbar roots that was used to establish a new adjuvant pharmacological treatment. Chronic treatment (up to 6 months) with NeuroHeal, a new combination drug therapy identified using a systems biology approach, exerted long-lasting neuroprotection, reduced gliosis and matrix proteoglycan content, accelerated nerve regeneration by activating the AKT pathway, promoted the formation of functional neuromuscular junctions, and reduced denervation-induced muscular atrophy. Thus, NeuroHeal is a promising treatment for spinal nerve root injuries and axonal regeneration after trauma.

  3. The TWEAK-Fn14 system: breaking the silence of cytokine-induced skeletal muscle wasting.

    Science.gov (United States)

    Bhatnagar, S; Kumar, A

    2012-01-01

    The occurrence of skeletal muscle atrophy, a devastating complication of a large number of disease states and inactivity/disuse conditions, provides a never ending quest to identify novel targets for its therapy. Proinflammatory cytokines are considered the mediators of muscle wasting in chronic diseases; however, their role in disuse atrophy has just begun to be elucidated. An inflammatory cytokine, tumor necrosis factor (TNF)- like weak inducer of apoptosis (TWEAK), has recently been identified as a potent inducer of skeletal muscle wasting. TWEAK activates various proteolytic pathways and stimulates the degradation of myofibril protein both in vitro and in vivo. Moreover, TWEAK mediates the loss of skeletal muscle mass and function in response to denervation, a model of disuse atrophy. Adult skeletal muscle express very low to minimal levels of TWEAK receptor, Fn14. Specific catabolic conditions such as denervation, immobilization, or unloading rapidly increase the expression of Fn14 in skeletal muscle which in turn stimulates the TWEAK activation of various catabolic pathways leading to muscle atrophy. In this article, we have discussed the emerging roles and the mechanisms of action of TWEAK-Fn14 system in skeletal muscle with particular reference to different models of muscle atrophy and injury and its potential to be used as a therapeutic target for prevention of muscle loss.

  4. [Healing process of claw lesions in dairy cows in alpine mountain pastures].

    Science.gov (United States)

    Lischer, C J; Wehrle, M; Geyer, H; Lutz, B; Ossent, P

    2000-07-01

    The field study investigated severity, localisation and incidence of claw lesions of dairy cows and their healing process during a period of three months on selected mountain pastures in the central part of Switzerland. In 60 cows, which were at least 120 days in their lactation, the healing process was compared with the biochemical profiles. In 141 cows 197 claw lesions were recorded. Diagnosed were only sole ulcers (38%) and white line lesions (62%). In the first and second half of the summer term, the number of claw lesions was equal, although more severe lesions occurred mainly during the second half (89%). The lesions were treated surgically and the affected claw was elevated on a wood block or a plastic shoe. Average time for formation of a close layer of horn was 14 days. A delayed healing process was observed in dairy cows with an milk yield over 5500 kg per lactation, as well as in the second half of the summer term. Cows with a delayed healing process had significantly higher concentrations of free fatty acids and beta-hydroxybutyrate, and higher plasma enzyme activities for AST than cows with adequate healing process. This indicates that cows with a relatively high milk production touch upon the limits of their physical capacity under harder conditions on alpine pastures, which may affect also the healing process of claw lesions.

  5. The fly wheel exercise device (FWED): A countermeasure against bone loss and muscle atrophy

    Science.gov (United States)

    Hueser, Detlev; Wolff, Christian; Berg, Hans E.; Tesch, Per A.; Cork, Michael

    2008-01-01

    The flywheel exercise device (FWED) is planned for use as an in-flight exercise system, to demonstrate its efficacy as a countermeasure device to prevent muscle atrophy, bone loss and impairment of muscle function in human beings in response to long duration spaceflight. It is intended to be used on the International Space Station (ISS) and will be launched by the European cargo carrier, the automated transfer vehicle (ATV) in late 2005. The FWED is a non-gravity-dependent mechanical device based on the Yo-Yo principle, which provides resistance during coupled concentric and eccentric muscle actions, through the inertia of a spinning flywheel. Currently, the development of a FWED Flight and Ground Model is in progress and is due to be completed in May 2004. An earlier developed prototype is available that has been used for various ground studies. Our FWED design provides a maximum of built-in safety and support to the operation by one astronaut. This is achieved in particular by innovative mechanical design features and an easy, safe to use man-machine interface. The modular design is optimized for efficient set-up and maintenance operations to be performed in orbit by the crew. The mechanical subsystem of the FWED includes a μg disturbance suspension, which minimizes the mechanical disturbances of the exercising subject at the mechanical interface to the ISS. During the FWED operation the astronaut is guided through the exercises by the data management subsystem, which acquires sensor data from the FWED, calculates and displays real-time feedback to the subject, and stores all data on hard disk and personalized storage media for later scientific analysis.

  6. Magnetic-resonance-imaging-based three-dimensional muscle reconstruction of hip abductor muscle volume in a person with a transfemoral bone-anchored prosthesis : A feasibility study

    NARCIS (Netherlands)

    Leijendekkers, Ruud A.; Marra, Marco A.; Ploegmakers, Marieke J.M.; Van Hinte, Gerben; Frölke, Jan Paul; Van De Meent, Hendrik; Staal, J. Bart; Hoogeboom, Thomas J.; Verdonschot, Nico

    2018-01-01

    Background: Persons with transfemoral amputation typically have severe muscle atrophy of the residual limb. The effect of bone-anchored prosthesis use on existing muscle atrophy is unknown. A potentially feasible method to evaluate this is magnetic resonance imaging (MRI)-based three-dimensional

  7. Progressive Hemifacial Atrophy with Morphea of Cheek

    Directory of Open Access Journals (Sweden)

    Ajit Auluck

    2006-01-01

    Full Text Available Scleroderma is a rare collagen disorder in which fibrosis of skin, subcutaneous tissues and muscles can occur with occasional involvement of bones. Localized scleroderma is a benign condition but can cause significant deformity when it affects the face. We report a case of localized scleroderma of the face causing progressive hemifacial atrophy.

  8. Genetic parameters for claw disorders and the effect of preselecting cows for trimming

    NARCIS (Netherlands)

    Spek, van der D.; Arendonk, van J.A.M.; Vallee, A.A.A.; Bovenhuis, H.

    2013-01-01

    Abstract Claw disorders are important traits relevant to dairy cattle breeding from an economical and welfare point of view. Selection for reduced claw disorders can be based on hoof trimmer records. Typically, not all cows in a herd are trimmed. Our objectives were to estimate heritabilities and

  9. Novel in vitro platform to investigate myotube atrophy.

    Science.gov (United States)

    Oelkrug, Christopher; Horn, Katharina; Makert, Gustavo R; Schubert, Andreas

    2015-04-01

    The electrical current exclusion (ECE) principle provides an alternative to common methods of cell diameter measurement and especially in atrophy and cancer associated cachexia research. C2C12 myoblasts were differentiated into myotubes and treated with 100 μM dexamethasone to induce atrophy in vitro. Subsequently, they were incubated for 24 h with media containing different concentrations of curcumin and/or branched-chain amino acids (BCAAs) in order to counteract atrophy. After treatment with curcumin, an increase in cell diameter was detectable; the highest increase with 13.9 ± 0.4% was seen with 10 μM curcumin. The combination of curcumin and BCAAs showed an increase of 13.4 ± 1.2 %. Cell diameter measurement via the ECE showed that curcumin, and curcumin in combination with BCAAs, were able to restore atrophic C2C12 myotubes. Therefore, the application of ECE in muscle atrophy and also cancer-associated cachexia research allows rapid screening of novel compounds in order to test their efficacy in vitro. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  10. Cancer cachexia decreases specific force and accelerates fatigue in limb muscle

    Energy Technology Data Exchange (ETDEWEB)

    Roberts, B. M. [1225 Center Drive, HPNP Building Room 1142, Department of Physical Therapy, University of Florida, Gainesville, FL 32610 (United States); Frye, G. S.; Ahn, B.; Ferreira, L. F. [1864 Stadium Road, Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL 32610 (United States); Judge, A.R., E-mail: arjudge@phhp.ufl.edu [1225 Center Drive, HPNP Building Room 1142, Department of Physical Therapy, University of Florida, Gainesville, FL 32610 (United States)

    2013-06-07

    Highlights: •C-26 cancer cachexia causes a significant decrease in limb muscle absolute force. •C-26 cancer cachexia causes a significant decrease in limb muscle specific force. •C-26 cancer cachexia decreases fatigue resistance in the soleus muscle. •C-26 cancer cachexia prolongs time to peak twitch tension in limb muscle. •C-26 cancer cachexia prolongs one half twitch relaxation time in limb muscle. -- Abstract: Cancer cachexia is a complex metabolic syndrome that is characterized by the loss of skeletal muscle mass and weakness, which compromises physical function, reduces quality of life, and ultimately can lead to mortality. Experimental models of cancer cachexia have recapitulated this skeletal muscle atrophy and consequent decline in muscle force generating capacity. However, more recently, we provided evidence that during severe cancer cachexia muscle weakness in the diaphragm muscle cannot be entirely accounted for by the muscle atrophy. This indicates that muscle weakness is not just a consequence of muscle atrophy but that there is also significant contractile dysfunction. The current study aimed to determine whether contractile dysfunction is also present in limb muscles during severe Colon-26 (C26) carcinoma cachexia by studying the glycolytic extensor digitorum longus (EDL) muscle and the oxidative soleus muscle, which has an activity pattern that more closely resembles the diaphragm. Severe C-26 cancer cachexia caused significant muscle fiber atrophy and a reduction in maximum absolute force in both the EDL and soleus muscles. However, normalization to muscle cross sectional area further demonstrated a 13% decrease in maximum isometric specific force in the EDL and an even greater decrease (17%) in maximum isometric specific force in the soleus. Time to peak tension and half relaxation time were also significantly slowed in both the EDL and the solei from C-26 mice compared to controls. Since, in addition to postural control, the oxidative

  11. Cancer cachexia decreases specific force and accelerates fatigue in limb muscle

    International Nuclear Information System (INIS)

    Roberts, B.M.; Frye, G.S.; Ahn, B.; Ferreira, L.F.; Judge, A.R.

    2013-01-01

    Highlights: •C-26 cancer cachexia causes a significant decrease in limb muscle absolute force. •C-26 cancer cachexia causes a significant decrease in limb muscle specific force. •C-26 cancer cachexia decreases fatigue resistance in the soleus muscle. •C-26 cancer cachexia prolongs time to peak twitch tension in limb muscle. •C-26 cancer cachexia prolongs one half twitch relaxation time in limb muscle. -- Abstract: Cancer cachexia is a complex metabolic syndrome that is characterized by the loss of skeletal muscle mass and weakness, which compromises physical function, reduces quality of life, and ultimately can lead to mortality. Experimental models of cancer cachexia have recapitulated this skeletal muscle atrophy and consequent decline in muscle force generating capacity. However, more recently, we provided evidence that during severe cancer cachexia muscle weakness in the diaphragm muscle cannot be entirely accounted for by the muscle atrophy. This indicates that muscle weakness is not just a consequence of muscle atrophy but that there is also significant contractile dysfunction. The current study aimed to determine whether contractile dysfunction is also present in limb muscles during severe Colon-26 (C26) carcinoma cachexia by studying the glycolytic extensor digitorum longus (EDL) muscle and the oxidative soleus muscle, which has an activity pattern that more closely resembles the diaphragm. Severe C-26 cancer cachexia caused significant muscle fiber atrophy and a reduction in maximum absolute force in both the EDL and soleus muscles. However, normalization to muscle cross sectional area further demonstrated a 13% decrease in maximum isometric specific force in the EDL and an even greater decrease (17%) in maximum isometric specific force in the soleus. Time to peak tension and half relaxation time were also significantly slowed in both the EDL and the solei from C-26 mice compared to controls. Since, in addition to postural control, the oxidative

  12. Claw disorders and disturbed locomotion in dairy cows: the effect of floor systems and implications for animal welfare

    NARCIS (Netherlands)

    Somers, Joan Gerardus Cornelius Johanna

    2004-01-01

    In modern dairy housing, flooring conditions lead to restricted locomotion and claw disorders. Epidemiological studies showed that housing on concrete floors was positively correlated with the incidence of lameness and claw disorders. Lameness and claw disorders constitute a significant health and

  13. Development of Human Muscle Protein Measurement with MRI

    Science.gov (United States)

    Lin, Chen; Evans, Harlan; Leblanc, Adrian D.

    1997-01-01

    It is known that micro-gravity has a strong influence on the human musculoskeletal system. A number of studies have shown that significant changes in skeletal muscles occur in both space flight and bedrest simulation. In our 5 week bedrest study, the cross-sectional area of soleus-gastrocnemius decreased about 12% while the cross-sectional area of anterior calf muscles decreased about 4%. Using volume measurements, these losses increased after 17 weeks to approximately 30% and 21% respectively. Significant muscle atrophy was also found on the SL-J crew members after only 8 days in space. It is important that these effects are fully understood so that countermeasures can be developed. The same knowledge might also be useful in preventing muscle atrophy related to other medical problems. A major problem with anatomical measurements of muscle during bed rest and microgravity is the influence of fluid shifts and water balance on the measurement of muscle volume, especially when the exposure duration is short and the atrophy is relatively small. Fluid shifts were documented in Skylab by visual observations of blood vessel distention, rapid changes in limb volume, center of mass measurements and subjective descriptions such as puffy faces and head fullness. It has been reported that the muscle water content of biopsied soleus muscles decreased following 8 hours of head down tilt bed rest. Three aspects of fluid shifts that can affect volume measurements are: first, the shift of fluid that occurs whenever there is a change from upright to a recumbent position and vice versa; second, the potential for fluid accumulation in the lower limbs resulting from muscle damage caused by overextending atrophied muscle or swelling caused by deconditioned precapillary sphincter muscles during reambulation; third, the net change of hydration level during and after bed rest or spaceflight. Because of these transitory fluid shifts, muscle protein is expected to represent muscle capacity

  14. Seasonal Patterns in Hydrogen Isotopes of Claws from Breeding Wood-Warblers (Parulidae: Utility for Estimating Migratory Origins

    Directory of Open Access Journals (Sweden)

    Kevin C. Fraser

    2008-06-01

    Full Text Available The global decline in many species of migratory birds has focused attention on the extent of migratory connectivity between breeding and wintering populations. Stable-hydrogen isotope (δD analysis of feathers is a useful technique for measuring connectivity, but is constrained by features of molt location and timing. Claws are metabolically inert, keratinous tissues that grow continuously and can be sampled at any point in the annual cycle, thus providing potentially useful clues about an individual's previous movements. However, variation in the rate at which claws incorporate local δD values is not well described. We measured δD values in claws of two species of Neotropical-Nearctic migrant wood-warblers (Golden-winged Warbler and Cerulean Warbler breeding in eastern Ontario, Canada to investigate the rate of δD change through the breeding season and the utility of claw δD values for estimating migratory origins. δD values of claw tips from 66 different individuals, each sampled once during the breeding season, showed an average change of -0.3‰ to -0.4‰ per day in the direction of the expected local Ontario value. There were no significant sex or species differences in the rate of change. These results suggest δD values of claw tips in Parulids may reflect those of the non-breeding area for 3-7 weeks after arrival on the breeding grounds, and are useful estimators of non-breeding migratory origin. Our results also suggest that these species may leave the breeding ground before claw tips fully incorporate a local δD signature, as claws sampled at the end of the breeding season did not match locally grown feather and claw δD values. This is the first study to examine the seasonal rate of the change in δD values of claws in long-distance, insectivorous, migratory birds.

  15. Treatment of patella fracture by claw-like shape memory alloy.

    Science.gov (United States)

    Hao, Wei; Zhou, Lugang; Sun, Yujie; Shi, Peng; Liu, Hongzhi; Wang, Xin

    2015-07-01

    Titanium-nickel shape memory alloy (Ti-Ni SMA) is characterized by shape-memory effect, super-elasticity, excellent fatigue behavior, corrosion resistance, acceptable biocompatibility and high damping capacity. Claw-like Ti-Ni SMA fixator (SMA-claw) has been used to treat transverse fracture of patella. 29 patients (19 males, 10 females) aged from 21 to 71 years old (averaged 43.0 years old) have been received open reduction and internal fixation with SMA-claw from January 2011 to December 2011. After operation, patients have been received gradual knee function exercises, followed by radiographic analysis and Lysholm Knee Score at 1, 2, 3, 6, 9 and 12 months postoperation. The mean follow-up time was 11.48 months (25 patients finished, 1 lost after 6 months and 3 lost after 9 months). Radiographic bone union occurred at 2 months (7 patients) or 3 months (22 patients). Satisfied range of motion for the knee joint has been observed with 1.90/141.72° (hyperextension/flexion) at 3 months, 4.83/143.97° at 6 months, 4.82/144.82° at 9 months and 5.2/145° at 12 months postsurgery. The Ti-Ni SMA-claw fixator produced good osteosynthesis effect by continuous recovery stress with relatively simple and minimally invasive handling process, which can be introduced as an alternative to traditional tension band technique for treatment of patellar transverse fracture.

  16. The pathogenesis and treatment of cardiac atrophy in cancer cachexia.

    Science.gov (United States)

    Murphy, Kate T

    2016-02-15

    Cancer cachexia is a multifactorial syndrome characterized by a progressive loss of skeletal muscle mass associated with significant functional impairment. In addition to a loss of skeletal muscle mass and function, many patients with cancer cachexia also experience cardiac atrophy, remodeling, and dysfunction, which in the field of cancer cachexia is described as cardiac cachexia. The cardiac alterations may be due to underlying heart disease, the cancer itself, or problems initiated by the cancer treatment and, unfortunately, remains largely underappreciated by clinicians and basic scientists. Despite recent major advances in the treatment of cancer, little progress has been made in the treatment of cardiac cachexia in cancer, and much of this is due to lack of information regarding the mechanisms. This review focuses on the cardiac atrophy associated with cancer cachexia, describing some of the known mechanisms and discussing the current and future therapeutic strategies to treat this condition. Above all else, improved awareness of the condition and an increased focus on identification of mechanisms and therapeutic targets will facilitate the eventual development of an effective treatment for cardiac atrophy in cancer cachexia. Copyright © 2016 the American Physiological Society.

  17. Computed tomographic findings of leg muscles in the hemiplegics due to cerebrovascular accidents

    International Nuclear Information System (INIS)

    Odajima, Natsu; Ishiai, Sumio; Kotera, Minoru; Furukawa, Tetsuo; Tsukagoshi, Hiroshi.

    1986-01-01

    The computed tomography (CT) scan was performed in 52 hemiplegics due to cerebrovascular accidents and 12 normal controls on the mid-portion of the thigh and the largest-diameter section of the calf. Muscle size and average CT density of the muscle were measured. The salient feature was hypertrophic gracilis muscle of the hemiplegic side. Other muscles were more atrophied with lower CT density compared with those of the contralateral side. The size of the quadriceps muscle was especially small. The ratio of the quadriceps to all the thigh muscles in cross section was significantly smaller in affected side of hemiplegics than that of normal controls. This was observed even in normal side of the hemiplegics but the ratios of adductor and flexor muscles of the thigh showed no difference. Hypertrophy of gracilis muscle with high CT density was observed only on hemiplegic side. Muscle atrophies were marked in non-ambulatory patients. The ratios of quadriceps and saltorius muscles of thigh in non-ambulatory patients were significantly smaller than those of ambulatory patients. It could not be detected that there is relationship of the sevirity of the muscle atrophy and parietal lobe dysfunction. This atrophy considered to be the result of disuse of the paralyzed leg and pyramidal tract dysfunction. (author)

  18. Pattern analysis in MR imaging of muscle diseases

    International Nuclear Information System (INIS)

    Kaiser, W.A.; Schalke, B.C.G.

    1987-01-01

    Between March 1984 and March 1987, 161 patients with muscle diseases underwent MR imaging performed with a 1.0-T superconductive magnet. Forty-four had progressive muscular dystrophies, 25 had different types of myositis, 19 had spinal or neural muscular atrophies, 16 had myotonic dystrophy, 22 had metabolic disorders, and 35 had other muscle disease, including muscle tumors, posttraumatic muscular atrophies, and postradiation effects. The advantages of MR imaging are the high sensitivity and soft-tissue contrast, as well as the depiction of typical distribution patterns of affected muscle groups, which can be used in diagnosis, biopsy planning, and design of therapy

  19. Muscle and the physiology of locomotion. [in zero gravity

    Science.gov (United States)

    Rambaut, P. C.; Nicogossian, A. E.; Pool, S. L.

    1983-01-01

    NASA's past, current, and planned research on muscle deterioration at zero gravity and development of countermeasures are reviewed; Soviet studies are discussed as well. A definition of muscle mass and strength regulation factors, and improved measurement methods of muscle atrophy are needed. Investigations of tissue growth factors and their receptors, endogenous and exogenous anabolic protein synthesis stimulation, and a potential neurotropic factor are among the projects in progress or planned. At present, vigorous physical exercise during spaceflight is recommended as the most effective countermeasure against skeletal muscle atrophy.

  20. CT findings of leg muscles in the hemiplegics due to cerebrovascular accidents

    International Nuclear Information System (INIS)

    Odajima, Natsu; Ishiai, Sumio; Okiyama, Ryouichi; Furukawa, Tetsuo; Tsukagoshi, Hiroshi.

    1987-01-01

    Muscle wastings in hemiplegics due to cerebrovascular accidents were studied with CT scanning in the mid-portion of the thigh and largest-diameter section of the calf bilaterally. Muscle size and average CT density of muscle were measured. The 80 patients were classified into one of the following three stages of disability, i.e. stage 1, severely disabled (wheel-chair-bound but capable of self care [20 patients]); stage 2, moderately disabled (poorly ambulatory [41 patients]); and stage 3, mildly disabled (well ambulatory [19 patients]). Muscle cross-sectional area and CT density in both legs of non-ambulatory patients were smaller and lower than those of other groups. The atrophic change was marked in the affected side, but it was also noticeable in the non-affected side. Gracilis muscle was relatively well spared in all 3 stages. These CT findings of hemiplegics were similar to those of disuse atropy in patients with knee or hip joint lesions. Atrophy was seen first in the quadriceps in thigh and flexor muscle group in calf. These findings were similar to the systemic myogenic or neurogenic atrophies. Although gracilis and sartorius muscles were spared in these systemic deseases, only gracilis muscle was spared in hemiplegics and in patients with disuse atrophy. The ratios of the size of quadriceps, adductor group and sartorius muscle of thigh in affected side to that of non-affected side were smaller in more severely disabled group. Those of the other muscles showed no differences among each stages. In stage 3, there was significant negative correlation between the ratio of quadriceps muscle and periods from the attack. There was no relationship between the severity of the muscle atrophy and parietal lobe lesion. The atrophy is considered to be the result of disuse from immobilization. (author)

  1. Hybrid excited claw pole generator with skewed and non-skewed permanent magnets

    Science.gov (United States)

    Wardach, Marcin

    2017-12-01

    This article contains simulation results of the Hybrid Excited Claw Pole Generator with skewed and non-skewed permanent magnets on rotor. The experimental machine has claw poles on two rotor sections, between which an excitation control coil is located. The novelty of this machine is existence of non-skewed permanent magnets on claws of one part of the rotor and skewed permanent magnets on the second one. The paper presents the construction of the machine and analysis of the influence of the PM skewing on the cogging torque and back-emf. Simulation studies enabled the determination of the cogging torque and the back-emf rms for both: the strengthening and the weakening of magnetic field. The influence of the magnets skewing on the cogging torque and the back-emf rms have also been analyzed.

  2. Klinefelter′s syndrome associated with progressive muscular atrophy simulating Kennedy′s disease

    OpenAIRE

    Pedro Enrique Jiménez Caballero

    2012-01-01

    Kennedy's disease, an X-linked spinal and bulbar muscular atrophy, is characterized by loss of lower motor neurons. Mild sensory deficits, gynecomastia and infertility may be observed. Klinefelter's syndrome is a variation of sex chromosome disorder characterized by hypogonadism, gynecomastia and azoospermia, and the most frequent karyotype is XXY. A 55-year-old man who presented with slowly progressive and diffuse neurogenic muscle atrophy without bulbar or sensory symptoms. He also had Klin...

  3. Rehabilitation and nutritional support for sarcopenic dysphagia and tongue atrophy after glossectomy: A case report.

    Science.gov (United States)

    Hashida, Nao; Shamoto, Hiroshi; Maeda, Keisuke; Wakabayashi, Hidetaka; Suzuki, Motoyuki; Fujii, Takashi

    2017-03-01

    Swallowing dysfunction is related to long-term weight loss and reduced body mass index in patients with head and neck cancer. We describe a 76-y-old woman who had severe sarcopenic dysphagia and atrophy of the reconstructed tongue for 17 mo after subtotal glossectomy due to tongue cancer and lost 14 kg during that period. Upon admission, the patient received diagnoses of malnutrition in the context of social or environmental circumstances with insufficient energy intake, loss of muscle mass, localized fluid accumulation, weight loss, and sarcopenia due to reduced skeletal muscle mass (skeletal muscle index protein intake to 70.3 g/d by supplying sufficient excess energy, and provided physical therapy and dysphagia rehabilitation to improve sarcopenia, atrophy of the reconstructed tongue, and dysphagia. After 20 mo of treatment, she was considered to be no longer malnourished (11 kg weight gain) and without sarcopenia (skeletal muscle index 4.01 cm 2 /m 2 ), and the volume of the reconstructed tongue was increased. Sarcopenia and atrophy of the reconstructed tongue may cause dysphagia after glossectomy due to tongue cancer. Additionally, nutritional support and rehabilitation could improve such dysphagia. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Effect of Constraint Loading on the Lower Limb Muscle Forces in Weightless Treadmill Exercise

    Directory of Open Access Journals (Sweden)

    Ning Guo

    2018-01-01

    Full Text Available Long exposure to the microgravity will lead to muscle atrophy and bone loss. Treadmill exercise could mitigate the musculoskeletal decline. But muscle atrophy remains inevitable. The constraint loading applied on astronauts could affect the muscle force and its atrophy severity. However, the quantitative correlation between constraint loading mode and muscle forces remains unclear. This study aimed to characterize the influence of constraint loading mode on the lower limb muscle forces in weightless treadmill exercise. The muscle forces in the full gait cycle were calculated with the inverse dynamic model of human musculoskeletal system. The calculated muscle forces at gravity were validated with the EMG data. Muscle forces increased at weightlessness compared with those at the earth’s gravity. The increasing percentage from high to low is as follows: biceps femoris, gastrocnemius, soleus, vastus, and rectus femoris, which was in agreement with the muscle atrophy observed in astronauts. The constraint loading mode had an impact on the muscle forces in treadmill exercise and thus could be manipulated to enhance the effect of the muscle training in spaceflight. The findings could provide biomechanical basis for the optimization of treadmill constraint system and training program and improve the countermeasure efficiency in spaceflight.

  5. A comparative analysis of fatty infiltration and muscle atrophy in patients with chronic rotator cuff tears and suprascapular neuropathy.

    Science.gov (United States)

    Beeler, Silvan; Ek, Eugene T H; Gerber, Christian

    2013-11-01

    Little is known of the mechanisms that lead to the muscle changes associated with rotator cuff disorders. We have observed that the magnetic resonance imaging (MRI) appearance of fatty infiltration (FI) and muscle atrophy (MA) differ between chronic cuff tears and suprascapular neuropathy, suggesting different pathophysiology. This study compares the different MRI changes that occur in chronic cuff tears and suprascapular neuropathy. Two groups were retrospectively identified: (1) RCT group (20 shoulders): patients with chronic tears of the supraspinatus and/or infraspinatus without electromyographic (EMG) evidence of suprascapular neuropathy; (2) neuro group (17 shoulders): patients with EMG documented suprascapular nerve dysfunction and absence of a rotator cuff tear. Magnetic resonance arthrograms were analyzed for the degree of FI and MA, and the morphology of the muscle was assessed, in particular the muscle border, pattern of FI, and extent of involvement. The muscle changes that occur following chronic cuff tears differ from that following denervation secondary to suprascapular neuropathy, especially with respect to the muscle border, degree of perineural fat, and overall distribution of FI. Highly specific and characteristic morphological patterns of FI exist for both chronic cuff tears and suprascapular neuropathy. Chronic rotator cuff tendon tears and suprascapular neuropathy are both associated with FI and MA of the rotator cuff muscles. The pattern of FI is markedly different in the 2 situations. These findings have diagnostic potential and may serve as a basis for further research concerning type, severity, and evolution of FI under different conditions and after treatment. Copyright © 2013 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.

  6. Differential alterations in gene expression profiles contribute to time-dependent effects of nandrolone to prevent denervation atrophy

    Directory of Open Access Journals (Sweden)

    Bauman William A

    2010-10-01

    Full Text Available Abstract Background Anabolic steroids, such as nandrolone, slow muscle atrophy, but the mechanisms responsible for this effect are largely unknown. Their effects on muscle size and gene expression depend upon time, and the cause of muscle atrophy. Administration of nandrolone for 7 days beginning either concomitantly with sciatic nerve transection (7 days or 29 days later (35 days attenuated denervation atrophy at 35 but not 7 days. We reasoned that this model could be used to identify genes that are regulated by nandrolone and slow denervation atrophy, as well as genes that might explain the time-dependence of nandrolone effects on such atrophy. Affymetrix microarrays were used to profile gene expression changes due to nandrolone at 7 and 35 days and to identify major gene expression changes in denervated muscle between 7 and 35 days. Results Nandrolone selectively altered expression of 124 genes at 7 days and 122 genes at 35 days, with only 20 genes being regulated at both time points. Marked differences in biological function of genes regulated by nandrolone at 7 and 35 days were observed. At 35, but not 7 days, nandrolone reduced mRNA and protein levels for FOXO1, the mTOR inhibitor REDD2, and the calcineurin inhibitor RCAN2 and increased those for ApoD. At 35 days, correlations between mRNA levels and the size of denervated muscle were negative for RCAN2, and positive for ApoD. Nandrolone also regulated genes for Wnt signaling molecules. Comparison of gene expression at 7 and 35 days after denervation revealed marked alterations in the expression of 9 transcriptional coregulators, including Ankrd1 and 2, and many transcription factors and kinases. Conclusions Genes regulated in denervated muscle after 7 days administration of nandrolone are almost entirely different at 7 versus 35 days. Alterations in levels of FOXO1, and of genes involved in signaling through calcineurin, mTOR and Wnt may be linked to the favorable action of nandrolone on

  7. The pressure distribution under the bovine claw during square standing on a flat substrate.

    NARCIS (Netherlands)

    Tol, van der P.P.J.; Metz, J.H.M.; Noordhuizen-Stassen, E.N.; Back, W.; Braam, C.R.; Weijs, W.A.

    2002-01-01

    The distribution pattern of pressure over the bovine claw was investigated to test the hypothesis that the ground reaction force is unevenly distributed and makes some regions of the claw more prone to overloading and injury than others. In eight recently trimmed Holstein Friesian cows, the

  8. In vivo 31P-NMR studies on the energy metabolism of atrophic muscles in rate

    International Nuclear Information System (INIS)

    Yamagiwa, Tetsuo

    1988-01-01

    Using P-31 NMR spectra, energy metabolism in the rat calf muscle was examined. The body weight in the atrophy and control groups did not differ significantly. Both the wet weight and dry weight of the calf muscle were significantly lower in the atrophy group than the control group. The muscle weight relative to the body weight was significantly lower in the atrophy group as well than the control group. There was no significant difference in the P-31 NMR spectral pattern before tourniquet ischemia between the atrophy and control groups. Rapid decrease in phosphocreatine (PCr) and rapid increase in inorganic phosphate (Pi) were observed in both groups immediately after application of the tourniquet; however, the rates of these changes were slightly greater and the PCr/Pi ratio in the peak values was significantly smaller in the atrophy group than the control group. The pH value before the ischemia was 7.15 ± 0.02 for the control group and 7.16 ± 0.02 for the atrophy group, with no significant difference between the groups. During ischemia, the pH value decreased progressively in the two groups; however, it became significantly decreased in the atrophy group from 10 to 60 min after application of tourniquet. The decrease in pH became gradual 60 min later. Since the decrease in pH was more rapid in the atrophic muscle than the intact muscle, this buffering capacity seems to be reduced in the atrophic muscle. (N.K.)

  9. Evaluation of muscle strength and motor abilities in children with type II and III spinal muscle atrophy treated with valproic acid

    Directory of Open Access Journals (Sweden)

    Zanoteli Edmar

    2011-03-01

    Full Text Available Abstract Background Spinal muscular atrophy (SMA is an autosomal recessive disorder that affects the motoneurons of the spinal anterior horn, resulting in hypotonia and muscle weakness. The disease is caused by deletion or mutation in the telomeric copy of SMN gene (SMN1 and clinical severity is in part determined by the copy number of the centromeric copy of the SMN gene (SMN2. The SMN2 mRNA lacks exon 7, resulting in a production of lower amounts of the full-length SMN protein. Knowledge of the molecular mechanism of diseases has led to the discovery of drugs capable of increasing SMN protein level through activation of SMN2 gene. One of these drugs is the valproic acid (VPA, a histone deacetylase inhibitor. Methods Twenty-two patients with type II and III SMA, aged between 2 and 18 years, were treated with VPA and were evaluated five times during a one-year period using the Manual Muscle Test (Medical Research Council scale-MRC, the Hammersmith Functional Motor Scale (HFMS, and the Barthel Index. Results After 12 months of therapy, the patients did not gain muscle strength. The group of children with SMA type II presented a significant gain in HFMS scores during the treatment. This improvement was not observed in the group of type III patients. The analysis of the HFMS scores during the treatment period in the groups of patients younger and older than 6 years of age did not show any significant result. There was an improvement of the daily activities at the end of the VPA treatment period. Conclusion Treatment of SMA patients with VPA may be a potential alternative to alleviate the progression of the disease. Trial Registration ClinicalTrials.gov: NCT01033331

  10. Head and Arm Tremor in X-linked Spinal and Bulbar Muscular Atrophy

    Directory of Open Access Journals (Sweden)

    Irene Aicua

    2014-10-01

    Full Text Available Background: X‐linked spinal and bulbar muscular atrophy (SBMA is a rare adult‐onset neuronopathy. Although tremor is known to occur in this disease, the number of reported cases of SBMA with tremor is rare, and the number with videotaped documentation is exceedingly rare. Our aim was to describe/document the characteristic signs of tremor in spinal and bulbar muscular atrophy.Case Report: We report a case of a 58‐year‐old male with a positive family history of tremor. On examination, the patient had jaw and hand tremors but he also exhibited gynecomastia, progressive bulbar paresis, and wasting and weakness primarily in the proximal limb muscles. The laboratory tests revealed an elevated creatine phosphokinase. Genetic testing was positive for X‐SBMA, with 42 CAG repeats.Discussion: Essential tremor is one of the most common movement disorders, yet it is important for clinicians to be aware of the presence of other distinguishing features that point to alternative diagnoses. The presence of action tremor associated with muscle atrophy and gynecomastia should lead to a suspicion of SBMA.

  11. Claw-pole Synchronous Generator for Compressed Air Energy Storage

    Directory of Open Access Journals (Sweden)

    PAVEL Valentina

    2013-05-01

    Full Text Available This paper presents a claw-poles generator for compressed air energy storage systems. It is presented the structure of such a system used for compensating of the intermittency of a small wind energy system. For equipping of this system it is chosen the permanent magnet claw pole synchronous generator obtained by using ring NdFeB permanentmagnets instead of excitation coil. In such a way the complexity of the scheme is reduced and the generator become maintenance free. The new magnetic flux density in the air-gap is calculated by magneticreluctance method and by FEM method and the results are compared with measured values in the old and new generator.

  12. PetClaw: Parallelization and Performance Optimization of a Python-Based Nonlinear Wave Propagation Solver Using PETSc

    KAUST Repository

    Alghamdi, Amal Mohammed

    2012-04-01

    Clawpack, a conservation laws package implemented in Fortran, and its Python-based version, PyClaw, are existing tools providing nonlinear wave propagation solvers that use state of the art finite volume methods. Simulations using those tools can have extensive computational requirements to provide accurate results. Therefore, a number of tools, such as BearClaw and MPIClaw, have been developed based on Clawpack to achieve significant speedup by exploiting parallel architectures. However, none of them has been shown to scale on a large number of cores. Furthermore, these tools, implemented in Fortran, achieve parallelization by inserting parallelization logic and MPI standard routines throughout the serial code in a non modular manner. Our contribution in this thesis research is three-fold. First, we demonstrate an advantageous use case of Python in implementing easy-to-use modular extensible scalable scientific software tools by developing an implementation of a parallelization framework, PetClaw, for PyClaw using the well-known Portable Extensible Toolkit for Scientific Computation, PETSc, through its Python wrapper petsc4py. Second, we demonstrate the possibility of getting acceptable Python code performance when compared to Fortran performance after introducing a number of serial optimizations to the Python code including integrating Clawpack Fortran kernels into PyClaw for low-level computationally intensive parts of the code. As a result of those optimizations, the Python overhead in PetClaw for a shallow water application is only 12 percent when compared to the corresponding Fortran Clawpack application. Third, we provide a demonstration of PetClaw scalability on up to the entirety of Shaheen; a 16-rack Blue Gene/P IBM supercomputer that comprises 65,536 cores and located at King Abdullah University of Science and Technology (KAUST). The PetClaw solver achieved above 0.98 weak scaling efficiency for an Euler application on the whole machine excluding the

  13. The genetics of muscle atrophy and growth: the impact and implications of polymorphisms in animals and humans.

    Science.gov (United States)

    Gordon, Erynn S; Gordish Dressman, Heather A; Hoffman, Eric P

    2005-10-01

    Much of the vast diversity we see in animals and people is governed by genetic loci that have quantitative effects of phenotype (quantitative trait loci; QTLs). Here we review the current knowledge of the genetics of atrophy and hypertrophy in both animal husbandry (meat quantity and quality), and humans (muscle size and performance). The selective breeding of animals for meat has apparently led to a few genetic loci with strong effects, with different loci in different animals. In humans, muscle quantitative trait loci (QTLs) appear to be more complex, with few "major" loci identified to date, although this is likely to change in the near future. We describe how the same phenotypic traits we see as positive, greater lean muscle mass in cattle or a better exercise results in humans, can also have negative "side effects" given specific environmental challenges. We also discuss the strength and limitations of single nucleotide polymorphisms (SNP) association studies; what the reader should look for and expect in a published study. Lastly we discuss the ethical and societal implications of this genetic information. As more and more research into the genetic loci that dictate phenotypic traits become available, the ethical implications of testing for these loci become increasingly important. As a society, most accept testing for genetic diseases or susceptibility, but do we as easily accept testing to determine one's athletic potential to be an Olympic endurance runner, or quarterback on the high school football team.

  14. CHEMICAL COMPOSITION VARIABILITY IN THE Uncaria tomentosa (cat’s claw WILD POPULATION

    Directory of Open Access Journals (Sweden)

    Evelyn Maribel Condori Peñaloza

    2015-03-01

    Full Text Available Uncaria tomentosa (cat's claw is a vine widely distributed throughout the South-American rainforest. Many studies investigating the chemical composition of cat's claw have focused on the pentacyclic (POA and tetracyclic oxindole alkaloids (TOA, quinovic acid glycosides (QAG, and polyphenols (PPH. Nevertheless, it is still uncertain how environmental factors affect chemical groups. The aim of this work was to better understand the influence of environmental factors (geographic origin, altitude, and season on cat's claw chemical composition. Stem bark, branches and leaf samples were extracted and analyzed by HPLC-PDA. The data obtained were explored by multivariate analysis (HCA and PCA. Higher amounts of oxindole alkaloids and PPH were found in leaves, followed by stem bark and branches. No clear relationship was verified among geographic origin or altitude and chemical composition, which remained unchanged regardless of season (dry or rainy. However, three oxindole alkaloid chemotypes were clearly recognized: chemotype I (POA with cis D/E ring junction; chemotype II (POA with trans D/E ring junction; and chemotype III (TOA. Thus, environmental factors appear to have only a minor influence on the chemical heterogeneity of the cat's claw wild population. Nevertheless, the occurrence of different chemotypes based on alkaloid profiles seems to be clear.

  15. Hybrid excited claw pole generator with skewed and non-skewed permanent magnets

    Directory of Open Access Journals (Sweden)

    Wardach Marcin

    2017-12-01

    Full Text Available This article contains simulation results of the Hybrid Excited Claw Pole Generator with skewed and non-skewed permanent magnets on rotor. The experimental machine has claw poles on two rotor sections, between which an excitation control coil is located. The novelty of this machine is existence of non-skewed permanent magnets on claws of one part of the rotor and skewed permanent magnets on the second one. The paper presents the construction of the machine and analysis of the influence of the PM skewing on the cogging torque and back-emf. Simulation studies enabled the determination of the cogging torque and the back-emf rms for both: the strengthening and the weakening of magnetic field. The influence of the magnets skewing on the cogging torque and the back-emf rms have also been analyzed.

  16. Genetic parameters for claw disorders in Dutch dairy cattle and correlations with conformation traits

    NARCIS (Netherlands)

    Waaij, van der E.H.; Holzhauer, M.; Ellen, E.D.; Kamphuis, C.; Jong, de G.

    2005-01-01

    Impaired claw health is one of the major problems causing production loss and reduced animal welfare in dairy cattle. In response, the Dutch Animal Health Service (GD) Ltd. initiated this study, in which claws of lactating and near-term cows and heifers in 430 herds were trimmed by hoof trimmers and

  17. Peripheral Androgen Receptor Gene Suppression Rescues Disease in Mouse Models of Spinal and Bulbar Muscular Atrophy

    Directory of Open Access Journals (Sweden)

    Andrew P. Lieberman

    2014-05-01

    Full Text Available Spinal and bulbar muscular atrophy (SBMA is caused by the polyglutamine androgen receptor (polyQ-AR, a protein expressed by both lower motor neurons and skeletal muscle. Although viewed as a motor neuronopathy, data from patients and mouse models suggest that muscle contributes to disease pathogenesis. Here, we tested this hypothesis using AR113Q knockin and human bacterial artificial chromosome/clone (BAC transgenic mice that express the full-length polyQ-AR and display androgen-dependent weakness, muscle atrophy, and early death. We developed antisense oligonucleotides that suppressed AR gene expression in the periphery but not the CNS after subcutaneous administration. Suppression of polyQ-AR in the periphery rescued deficits in muscle weight, fiber size, and grip strength, reversed changes in muscle gene expression, and extended the lifespan of mutant males. We conclude that polyQ-AR expression in the periphery is an important contributor to pathology in SBMA mice and that peripheral administration of therapeutics should be explored for SBMA patients.

  18. Do culverts impact the movements of the endangered white-clawed crayfish?

    Directory of Open Access Journals (Sweden)

    Louca V.

    2014-01-01

    Full Text Available Culverts can impact the migration and dispersal of aquatic animals and result in population fragmentation, increasing the risk of local extinction for endangered species such as the white-clawed crayfish Austropotamobius pallipes. This study used radio telemetry and passive integrated transponder (PIT telemetry to determine whether existing and experimental covered culverts affect the upstream and downstream movements of adult white-clawed crayfish. Daily crayfish movement rates did not differ significantly between an unlit 363-m long culvert and open stream channel sections. Crayfish moved into dark, covered sections volitionally. However, limited upstream movement occurred at sudden transitions of bed height or smooth-concrete box culvert sections with fast flow, suggesting partial barrier effects. In the 20-m long experimental in-stream culvert, also dark, but with natural stream bed, 70% of radio-tagged crayfish released downstream entered the culvert, as did 60% of those released upstream. Overall 35% passed through, with similar numbers in each direction. We conclude that dark culverts up to several hundred metres do not inhibit dispersal of white-clawed crayfish, provided stream slope, bed type and water velocity are amenable for movement and refuge. Care is required to ensure that culverts are bioengineered to ensure that average water velocity is sufficiently low and local hydraulic variation high, the bed and/or sidewalls contain refuge structures, and there are no cross-channel steps in bed level. Smooth-bedded box culverts are unlikely to be suitable for white-clawed crayfish.

  19. Inadequate thickness of the weight-bearing surface of claws in ruminants : clinical review

    Directory of Open Access Journals (Sweden)

    A.S. Shakespeare

    2009-05-01

    Full Text Available The term 'thin soles' refers to the suboptimal thickness of the weight-bearing surface of claws in ruminants. These palmar / plantar surfaces of the claws support the weight of the animal and consist of the distal wall horn, the sole proper, the heel and the minute white line area. The sole should normally only bear weight on uneven or undulating surfaces. A decrease in the thickness of the weight-bearing claw surface will decrease the protective function of this structure and may alter the proportion of weight-bearing by each section with possible detrimental effects on hoof function. Horn tissue readily absorbs water and becomes softer which can lead to increased wear rates. Growth rates normally match wear rates but, unlike the latter, time is needed for the growth rate response to adapt to changes in wear rate. Concrete surfaces can be abrasive and dairy cows that spend their lactation cycle on these floors should be let out to pasture in the dry period so that their claws can recoup lost horn. Frictional coefficient is a measure of the 'slipperiness' of hooves on various surfaces. Newly laid or fresh concrete is not only abrasive but the thin surface suspension of calcium hydroxide that forms has a very alkaline pH which causes keratin degradation and is mostly responsible for the excessive claw wear that occurs. Four case studies are used to illustrate the importance of the distal wall horn, the dangers of over-trimming and the effects of disease and concrete on horn growth and wear rates.

  20. β-Hydroxy-β-methylbutyrate reduces myonuclear apoptosis during recovery from hind limb suspension-induced muscle fiber atrophy in aged rats

    Science.gov (United States)

    Hao, Yanlei; Jackson, Janna R.; Wang, Yan; Edens, Neile; Pereira, Suzette L.

    2011-01-01

    β-Hydroxy-β-methylbutyrate (HMB) is a leucine metabolite shown to reduce protein catabolism in disease states and promote skeletal muscle hypertrophy in response to loading exercise. In this study, we evaluated the efficacy of HMB to reduce muscle wasting and promote muscle recovery following disuse in aged animals. Fisher 344×Brown Norway rats, 34 mo of age, were randomly assigned to receive either Ca-HMB (340 mg/kg body wt) or the water vehicle by gavage (n = 32/group). The animals received either 14 days of hindlimb suspension (HS, n = 8/diet group) or 14 days of unloading followed by 14 days of reloading (R; n = 8/diet group). Nonsuspended control animals were compared with suspended animals after 14 days of HS (n = 8) or after R (n = 8). HMB treatment prevented the decline in maximal in vivo isometric force output after 2 wk of recovery from hindlimb unloading. The HMB-treated animals had significantly greater plantaris and soleus fiber cross-sectional area compared with the vehicle-treated animals. HMB decreased the amount of TUNEL-positive nuclei in reloaded plantaris muscles (5.1% vs. 1.6%, P HMB did not significantly alter Bcl-2 protein abundance compared with vehicle treatment, HMB decreased Bax protein abundance following R, by 40% and 14% (P HMB-treated reloaded plantaris and soleus muscles, compared with vehicle-treated animals. HMB reduced cleaved caspase-9 by 14% and 30% (P HMB was unable to prevent unloading-induced atrophy, it attenuated the decrease in fiber area in fast and slow muscles after HS and R. HMB's ability to protect against muscle loss may be due in part to putative inhibition of myonuclear apoptosis via regulation of mitochondrial-associated caspase signaling. PMID:21697520

  1. Mapping of the bovine spinal muscular atrophy locus to Chromosome 24.

    Science.gov (United States)

    Medugorac, Ivica; Kemter, Juliane; Russ, Ingolf; Pietrowski, Detlef; Nüske, Stefan; Reichenbach, Horst-Dieter; Schmahl, Wolfgang; Förster, Martin

    2003-06-01

    A hereditary form of spinal muscular atrophy (SMA) caused by an autosomal recessive gene has been reported for American Brown-Swiss cattle and in advanced backcrosses between American Brown-Swiss and many European brown cattle breeds. Bovine SMA (bovSMA) bears remarkable resemblance to the human SMA (SMA1). Affected homozygous calves also show progressive symmetric weakness and neurogenic atrophy of proximal muscles. The condition is characterized by severe muscle atrophy, quadriparesis, and sternal recumbency as result of neurogenic atrophy. We report on the localization of the gene causing bovSMA within a genomic interval between the microsatellite marker URB031 and the telomeric end of bovine Chromosome (Chr) 24 (BTA24). Linkage analysis of a complex pedigree of German Braunvieh cattle revealed a recombination fraction of 0.06 and a three-point lod score of 11.82. The results of linkage and haplotyping analysis enable a marker-assisted selection against bovSMA based on four microsatellite markers most telomeric on BTA24 to a moderate accuracy of 89-94%. So far, this region is not orthologous to any human chromosome segments responsible for twelve distinct disease phenotypes of autosomal neuropathies. Our results indicate the apoptosis-inhibiting protein BCL2 as the most promising positional candidate gene causing bovSMA. Our findings offer an attractive animal model for a better understanding of human forms of SMA and for a probable anti-apoptotic synergy of SMN-BCL2 aggregates in mammals.

  2. The Genome of the Western Clawed Frog Xenopus tropicalis

    Energy Technology Data Exchange (ETDEWEB)

    Hellsten, Uffe; Harland, Richard M.; Gilchrist, Michael J.; Hendrix, David; Jurka, Jerzy; Kapitonov, Vladimir; Ovcharenko, Ivan; Putnam, Nicholas H.; Shu, Shengqiang; Taher, Leila; Blitz, Ira L.; Blumberg, Bruce; Dichmann, Darwin S.; Dubchak, Inna; Amaya, Enrique; Detter, John C.; Fletcher, Russell; Gerhard, Daniela S.; Goodstein, David; Graves, Tina; Grigoriev, Igor V.; Grimwood, Jane; Kawashima, Takeshi; Lindquist, Erika; Lucas, Susan M.; Mead, Paul E.; Mitros, Therese; Ogino, Hajime; Ohta, Yuko; Poliakov, Alexander V.; Pollet, Nicolas; Robert, Jacques; Salamov, Asaf; Sater, Amy K.; Schmutz, Jeremy; Terry, Astrid; Vize, Peter D.; Warren, Wesley C.; Wells, Dan; Wills, Andrea; Wilson, Richard K.; Zimmerman, Lyle B.; Zorn, Aaron M.; Grainger, Robert; Grammer, Timothy; Khokha, Mustafa K.; Richardson, Paul M.; Rokhsar, Daniel S.

    2009-10-01

    The western clawed frog Xenopus tropicalis is an important model for vertebrate development that combines experimental advantages of the African clawed frog Xenopus laevis with more tractable genetics. Here we present a draft genome sequence assembly of X. tropicalis. This genome encodes over 20,000 protein-coding genes, including orthologs of at least 1,700 human disease genes. Over a million expressed sequence tags validated the annotation. More than one-third of the genome consists of transposable elements, with unusually prevalent DNA transposons. Like other tetrapods, the genome contains gene deserts enriched for conserved non-coding elements. The genome exhibits remarkable shared synteny with human and chicken over major parts of large chromosomes, broken by lineage-specific chromosome fusions and fissions, mainly in the mammalian lineage.

  3. A new approach to assess the gastrocnemius muscle volume in rodents using ultrasound; comparison with the gastrocnemius muscle index.

    Directory of Open Access Journals (Sweden)

    Tim H J Nijhuis

    Full Text Available INTRODUCTION: The purpose of this study was to determine the reliability and validity of a new non-invasive ultrasound technique to measure gastrocnemius muscle atrophy after nerve denervation in an animal model. METHODS: In sixteen rodents an eight mm sciatic nerve gap was created. In the following 8 weeks, each week, two rodents were euthanized and the gastrocnemius muscle was examined using two different ultrasound systems and two investigators. The standardized ultrasound measurement protocol consisted of identifying pre-defined anatomical landmarks: 1 the fibula, 2 the fibular nerve, and 3 the junction between the most distal point of the semitendinosus muscle and gastrocnemius muscle. Consequently, we measured the muscle thickness as the length of the line between the fibula and the junction between the two muscles, perpendicular to the fibular nerve. After the ultrasound recording, the muscle mass was determined. RESULTS: A steep decline of muscle weight of 24% was observed after one week. In the following weeks, the weight further decreased and then remained stable from 6 weeks onwards, resulting in a maximal muscle weight decrease of 82%. The correlation coefficient was >0.96 between muscle diameter and weight using both ultrasound systems. The inter-rater reliability was excellent for both devices on the operated side (ICC of 0.99 for both ultrasound systems and good for the non-operated site (ICC's: 0.84 & 0.89. The difference between the muscle mass ratio and the muscle thickness ratio was not more than 5% with two outliers of approximately 13%. DISCUSSION: We have developed an innovative, highly reliable technique for quantifying muscle atrophy after nerve injury. This technique allows serial measurements in the same animal over time. This is a significant advantage compared to the conventional technique for quantifying muscle atrophy, which requires sacrificing the animal.

  4. Short communication: Pilot study on hormonal, metabolic, and behavioral stress response to treatment of claw horn lesions in acutely lame dairy cows.

    Science.gov (United States)

    Janßen, S; Wunderlich, C; Heppelmann, M; Palme, R; Starke, A; Kehler, W; Steiner, A; Rizk, A; Meyer, U; Daenicke, S; Rehage, J

    2016-09-01

    Short-term effects of therapeutic claw trimming in acutely lame cows (n=21) with nonadvanced claw horn lesions on the endocrine, metabolic, and behavioral stress responses were investigated in comparison to regular claw trimming in nonlame control cows (n=21). Controls were matched to lame cows by parity and stage of lactation. Lame cows suffering from typical sole ulcers or white line disease were blinded and randomly assigned to 2 treatments, receiving 15 min before interventions either ketoprofen (n=11; 3mg/kg of BW intramuscularly; Romefen, Merial, Lyon, France) or placebo (n=10; saline in equivalent amount and route of administration). All cows underwent functional claw trimming in lateral recumbency on a surgical tipping table, and claw horn lesions in lame cows were conventionally treated (removal of loose horn, block on opposing claw, bandaging of affected claw). Blood samples collected 15 min before, at the end, and 24h after claw trimming were analyzed for concentrations of cortisol, fatty acids, lactate, and glucose, and fecal samples (collected before treatment and after 24 h) for cortisol metabolites. Behavioral stress responses during functional and therapeutic claw trimming were recorded. Concentrations of blood cortisol, fatty acids, glucose, and fecal cortisol metabolites were higher in lame than in nonlame cows after treatment. During claw treatment, more leg movements were recorded for lame cows than nonlame cows. Pre-emptive administration of ketoprofen had no obvious effects on stress responses to therapeutic claw trimming. Treatments of claw horn lesions caused a significant stress and pain reaction in acutely lame cows, demonstrating the necessity of adequate pain management protocols for such interventions. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  5. Claw health and prevalence of lameness in cows from compost bedded and cubicle freestall dairy barns in Austria.

    Science.gov (United States)

    Burgstaller, J; Raith, J; Kuchling, S; Mandl, V; Hund, A; Kofler, J

    2016-10-01

    Claw health and lameness data from five dairies with compost bedded barns (n = 201 data sets) were evaluated and compared with data from five dairy herds housed in freestall cubicle barns (n = 297 data sets). They were matched for having the same cow numbers, flooring type and similar milk yield. The prevalence of lameness, claw lesions and their severity grades were analysed. Two claw health indicators, the cow claw score (CCS) and the farm claw score (FCS), were calculated using a computerised claw trimming database programme; there was no significant difference in overall lameness prevalence in cows from five compost bedded barns (18.7%) compared to cows from five freestall cubicle herds (14.9%). A cumulative link mixed model (CLMM) did not show significant differences in locomotion between different types of bedding material, flooring system, breed, visit number, observer and time since last trimming, but locomotion was significantly influenced by CCS. Another CLMM tested the impact of parameters mentioned on CCS and showed significant influence of flooring type, visit number and cattle breed. Statistically significant differences in the prevalence of claw disorders between compost bedded and freestall cubicle barns were found for white line disease (WLD; 20.4% and 46.6%, respectively), heel horn erosion (HHE; 26.9% and 59.9%, respectively), concave dorsal wall as a result of chronic laminitis (6.5% and 15.9%, respectively) and for interdigital hyperplasia (0.2% and 3.1%, respectively). The results of this study indicate that compost dairy barns are a good alternative to common cubicle housing systems in terms of lameness, claw health and animal welfare. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Muscle MRI findings in facioscapulohumeral muscular dystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Gerevini, Simonetta; Caliendo, Giandomenico; Falini, Andrea [IRCCS San Raffaele Scientific Institute, Neuroradiology Unit, Head and Neck Department, Milan (Italy); Scarlato, Marina; Previtali, Stefano Carlo [IRCCS San Raffaele Scientific Institute, Department of Neurology, INSPE and Division of Neuroscience, Milan (Italy); Maggi, Lorenzo; Pasanisi, Barbara; Morandi, Lucia [Fondazione IRCCS Istituto Neurologico ' ' Carlo Besta' ' , Neuromuscular Diseases and Neuroimmunology Unit, Milan (Italy); Cava, Mariangela [IRCCS San Raffaele Scientific Institute, Department of Radiology and Center for Experimental Imaging, Milan (Italy)

    2016-03-15

    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. (orig.)

  7. Retropupillary Fixation of Iris-Claw Intraocular Lens for Aphakic Eyes in Children.

    Directory of Open Access Journals (Sweden)

    Martina Brandner

    Full Text Available To report outcome, complications and safety of retropupillary fixated iris-claw intraocular lenses in a pediatric population.Retrospective study.Ten consecutive pediatric patients (15 eyes underwent placement of retropupillary fixated iris-claw intraocular lenses between October 2007 and July 2013 at the Department of Ophthalmology, Medical University Graz and General Hospital Klagenfurt, Austria. Postoperative visual acuity and complications were analyzed.Median final best-corrected visual acuity improved by 0.12 logMAR from preoperative baseline. Mean postoperative spherical equivalent was -0.05 ± 1.76 D. No serious complications were observed intra- or postoperatively during the entire follow-up period of up to 40 months. One patient experienced a haptic disenclavation with IOL subluxation immediately after a car accident.Our study demonstrates that iris-claw intraocular lens implantation behind the iris is safe in children with lack of capsular support and yields excellent visual outcome with low complication rate.

  8. Retropupillary Fixation of Iris-Claw Intraocular Lens for Aphakic Eyes in Children

    Science.gov (United States)

    Brandner, Martina; Thaler-Saliba, Sarah; Plainer, Sophie; Vidic, Bertram; El-Shabrawi, Yosuf; Ardjomand, Navid

    2015-01-01

    Purpose To report outcome, complications and safety of retropupillary fixated iris-claw intraocular lenses in a pediatric population. Design Retrospective study. Patients and Methods Ten consecutive pediatric patients (15 eyes) underwent placement of retropupillary fixated iris-claw intraocular lenses between October 2007 and July 2013 at the Department of Ophthalmology, Medical University Graz and General Hospital Klagenfurt, Austria. Postoperative visual acuity and complications were analyzed. Results Median final best-corrected visual acuity improved by 0.12 logMAR from preoperative baseline. Mean postoperative spherical equivalent was -0.05 ± 1.76 D. No serious complications were observed intra- or postoperatively during the entire follow-up period of up to 40 months. One patient experienced a haptic disenclavation with IOL subluxation immediately after a car accident. Conclusion Our study demonstrates that iris-claw intraocular lens implantation behind the iris is safe in children with lack of capsular support and yields excellent visual outcome with low complication rate. PMID:26110864

  9. Foot ulcer risk and location in relation to prospective clinical assessment of foot shape and mobility among persons with diabetes.

    Science.gov (United States)

    Cowley, Matthew S; Boyko, Edward J; Shofer, Jane B; Ahroni, Jessie H; Ledoux, William R

    2008-11-01

    We assessed baseline clinical foot shape for 2939 feet of diabetic subjects who were monitored prospectively for foot ulceration. Assessments included hammer/claw toes, hallux valgus, hallux limitus, prominent metatarsal heads, bony prominences, Charcot deformity, plantar callus, foot type, muscle atrophy, ankle and hallux mobility, and neuropathy. Risk factors were linked to ulcer occurrence and location via a Cox proportional hazards model. Hammer/claw toes (hazard ratio [HR] (95% confidence interval [CI])=1.43 (1.06, 1.94) p=0.02), marked hammer/claw toes (HR=1.77 (1.18, 2.66) p=0.006), bony prominences (HR=1.38 (1.02, 1.88), p=0.04), and foot type (Charcot or drop foot vs. neutrally aligned) (HR=2.34 (1.33, 4.10), p=0.003) were significant risk factors for ulceration adjusting for age, body mass index, insulin medication, ulcer history and amputation history. With adjustment for neuropathy only hammer/claw toes (HR=1.40 (1.03, 1.90), p=0.03) and foot type (HR=1.76 (1.04, 3.04), p=0.05) were significantly related to ulceration. However, there was no relationship between ulcer location and foot deformity. Certain foot deformities were predictive of ulceration, although there was no relationship between clinical foot deformity and ulcer location.

  10. The complex of PAMAM-OH dendrimer with Angiotensin (1-7) prevented the disuse-induced skeletal muscle atrophy in mice.

    Science.gov (United States)

    Márquez-Miranda, Valeria; Abrigo, Johanna; Rivera, Juan Carlos; Araya-Durán, Ingrid; Aravena, Javier; Simon, Felipe; Pacheco, Nicolás; González-Nilo, Fernando Danilo; Cabello-Verrugio, Claudio

    2017-01-01

    Angiotensin (1-7) (Ang-(1-7)) is a bioactive heptapeptide with a short half-life and has beneficial effects in several tissues - among them, skeletal muscle - by preventing muscle atrophy. Dendrimers are promising vehicles for the protection and transport of numerous bioactive molecules. This work explored the use of a neutral, non-cytotoxic hydroxyl-terminated poly(amidoamine) (PAMAM-OH) dendrimer as an Ang-(1-7) carrier. Bioinformatics analysis showed that the Ang-(1-7)-binding capacity of the dendrimer presented a 2:1 molar ratio. Molecular dynamics simulation analysis revealed the capacity of neutral PAMAM-OH to protect Ang-(1-7) and form stable complexes. The peptide coverage ability of the dendrimer was between ~50% and 65%. Furthermore, an electrophoretic mobility shift assay demonstrated that neutral PAMAM-OH effectively bonded peptides. Experimental results showed that the Ang-(1-7)/PAMAM-OH complex, but not Ang-(1-7) alone, had an anti-atrophic effect when administered intraperitoneally, as evaluated by muscle strength, fiber diameter, myofibrillar protein levels, and atrogin-1 and MuRF-1 expressions. The results of the Ang-(1-7)/PAMAM-OH complex being intraperitoneally injected were similar to the results obtained when Ang-(1-7) was systemically administered through mini-osmotic pumps. Together, the results suggest that Ang-(1-7) can be protected for PAMAM-OH when this complex is intraperitoneally injected. Therefore, the Ang-(1-7)/PAMAM-OH complex is an efficient delivery method for Ang-(1-7), since it improves the anti-atrophic activity of this peptide in skeletal muscle.

  11. Vaginal Atrophy

    Science.gov (United States)

    ... an Endocrinologist Search Featured Resource Menopause Map™ View Vaginal Atrophy October 2017 Download PDFs English Editors Christine ... during this time, including vaginal dryness. What is vaginal atrophy? Vaginal atrophy (also referred to as vulvovaginal ...

  12. Angiotensin II Infusion Induces Marked Diaphragmatic Skeletal Muscle Atrophy

    Science.gov (United States)

    Rezk, Bashir M.; Yoshida, Tadashi; Semprun-Prieto, Laura; Higashi, Yusuke; Sukhanov, Sergiy; Delafontaine, Patrice

    2012-01-01

    Advanced congestive heart failure (CHF) and chronic kidney disease (CKD) are characterized by increased angiotensin II (Ang II) levels and are often accompanied by significant skeletal muscle wasting that negatively impacts mortality and morbidity. Both CHF and CKD patients have respiratory muscle dysfunction, however the potential effects of Ang II on respiratory muscles are unknown. We investigated the effects of Ang II on diaphragm muscle in FVB mice. Ang II induced significant diaphragm muscle wasting (18.7±1.6% decrease in weight at one week) and reduction in fiber cross-sectional area. Expression of the E3 ubiquitin ligases atrogin-1 and muscle ring finger-1 (MuRF-1) and of the pro-apoptotic factor BAX was increased after 24 h of Ang II infusion (4.4±0.3 fold, 3.1±0.5 fold and 1.6±0.2 fold, respectively, compared to sham infused control) suggesting increased muscle protein degradation and apoptosis. In Ang II infused animals, there was significant regeneration of injured diaphragm muscles at 7 days as indicated by an increase in the number of myofibers with centralized nuclei and high expression of embryonic myosin heavy chain (E-MyHC, 11.2±3.3 fold increase) and of the satellite cell marker M-cadherin (59.2±22.2% increase). Furthermore, there was an increase in expression of insulin-like growth factor-1 (IGF-1, 1.8±0.3 fold increase) in Ang II infused diaphragm, suggesting the involvement of IGF-1 in diaphragm muscle regeneration. Bone-marrow transplantation experiments indicated that although there was recruitment of bone-marrow derived cells to the injured diaphragm in Ang II infused mice (267.0±74.6% increase), those cells did not express markers of muscle stem cells or regenerating myofibers. In conclusion, Ang II causes marked diaphragm muscle wasting, which may be important for the pathophysiology of respiratory muscle dysfunction and cachexia in conditions such as CHF and CKD. PMID:22276172

  13. Angiotensin II infusion induces marked diaphragmatic skeletal muscle atrophy.

    Directory of Open Access Journals (Sweden)

    Bashir M Rezk

    Full Text Available Advanced congestive heart failure (CHF and chronic kidney disease (CKD are characterized by increased angiotensin II (Ang II levels and are often accompanied by significant skeletal muscle wasting that negatively impacts mortality and morbidity. Both CHF and CKD patients have respiratory muscle dysfunction, however the potential effects of Ang II on respiratory muscles are unknown. We investigated the effects of Ang II on diaphragm muscle in FVB mice. Ang II induced significant diaphragm muscle wasting (18.7±1.6% decrease in weight at one week and reduction in fiber cross-sectional area. Expression of the E3 ubiquitin ligases atrogin-1 and muscle ring finger-1 (MuRF-1 and of the pro-apoptotic factor BAX was increased after 24 h of Ang II infusion (4.4±0.3 fold, 3.1±0.5 fold and 1.6±0.2 fold, respectively, compared to sham infused control suggesting increased muscle protein degradation and apoptosis. In Ang II infused animals, there was significant regeneration of injured diaphragm muscles at 7 days as indicated by an increase in the number of myofibers with centralized nuclei and high expression of embryonic myosin heavy chain (E-MyHC, 11.2±3.3 fold increase and of the satellite cell marker M-cadherin (59.2±22.2% increase. Furthermore, there was an increase in expression of insulin-like growth factor-1 (IGF-1, 1.8±0.3 fold increase in Ang II infused diaphragm, suggesting the involvement of IGF-1 in diaphragm muscle regeneration. Bone-marrow transplantation experiments indicated that although there was recruitment of bone-marrow derived cells to the injured diaphragm in Ang II infused mice (267.0±74.6% increase, those cells did not express markers of muscle stem cells or regenerating myofibers. In conclusion, Ang II causes marked diaphragm muscle wasting, which may be important for the pathophysiology of respiratory muscle dysfunction and cachexia in conditions such as CHF and CKD.

  14. Skeletal muscle training for spinal muscular atrophy type 3 (Protocol).

    NARCIS (Netherlands)

    Bartels, B.; Montes, J.; Pol, W.L. van der; Groot, J.F. de

    2016-01-01

    Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disease caused by a genetic mutation in the survival motor neuron 1 (SMN1) gene (5q11.2-q13.3) (Lefebvre 1995). With an incidence of one in 10,000 live births, it is the leading genetic cause of infant death (Lunn 2008;

  15. Reconfiguring Independent Sets in Claw-Free Graphs

    NARCIS (Netherlands)

    Bonsma, P.S.; Kamiński, Marcin; Wrochna, Marcin; Ravi, R.; Gørtz, Inge Li

    We present a polynomial-time algorithm that, given two independent sets in a claw-free graph G, decides whether one can be transformed into the other by a sequence of elementary steps. Each elementary step is to remove a vertex v from the current independent set S and to add a new vertex w (not in

  16. Evidence for a grooming claw in a North American adapiform primate: implications for anthropoid origins.

    Directory of Open Access Journals (Sweden)

    Stephanie Maiolino

    Full Text Available Among fossil primates, the Eocene adapiforms have been suggested as the closest relatives of living anthropoids (monkeys, apes, and humans. Central to this argument is the form of the second pedal digit. Extant strepsirrhines and tarsiers possess a grooming claw on this digit, while most anthropoids have a nail. While controversial, the possible presence of a nail in certain European adapiforms has been considered evidence for anthropoid affinities. Skeletons preserved well enough to test this idea have been lacking for North American adapiforms. Here, we document and quantitatively analyze, for the first time, a dentally associated skeleton of Notharctus tenebrosus from the early Eocene of Wyoming that preserves the complete bones of digit II in semi-articulation. Utilizing twelve shape variables, we compare the distal phalanges of Notharctus tenebrosus to those of extant primates that bear nails (n = 21, tegulae (n = 4, and grooming claws (n = 10, and those of non-primates that bear claws (n = 7. Quantitative analyses demonstrate that Notharctus tenebrosus possessed a grooming claw with a surprisingly well-developed apical tuft on its second pedal digit. The presence of a wide apical tuft on the pedal digit II of Notharctus tenebrosus may reflect intermediate morphology between a typical grooming claw and a nail, which is consistent with the recent hypothesis that loss of a grooming claw occurred in a clade containing adapiforms (e.g. Darwinius masillae and anthropoids. However, a cladistic analysis including newly documented morphologies and thorough representation of characters acknowledged to have states constituting strepsirrhine, haplorhine, and anthropoid synapomorphies groups Notharctus tenebrosus and Darwinius masillae with extant strepsirrhines rather than haplorhines suggesting that the form of pedal digit II reflects substantial homoplasy during the course of early primate evolution.

  17. Evidence for a grooming claw in a North American adapiform primate: implications for anthropoid origins.

    Science.gov (United States)

    Maiolino, Stephanie; Boyer, Doug M; Bloch, Jonathan I; Gilbert, Christopher C; Groenke, Joseph

    2012-01-01

    Among fossil primates, the Eocene adapiforms have been suggested as the closest relatives of living anthropoids (monkeys, apes, and humans). Central to this argument is the form of the second pedal digit. Extant strepsirrhines and tarsiers possess a grooming claw on this digit, while most anthropoids have a nail. While controversial, the possible presence of a nail in certain European adapiforms has been considered evidence for anthropoid affinities. Skeletons preserved well enough to test this idea have been lacking for North American adapiforms. Here, we document and quantitatively analyze, for the first time, a dentally associated skeleton of Notharctus tenebrosus from the early Eocene of Wyoming that preserves the complete bones of digit II in semi-articulation. Utilizing twelve shape variables, we compare the distal phalanges of Notharctus tenebrosus to those of extant primates that bear nails (n = 21), tegulae (n = 4), and grooming claws (n = 10), and those of non-primates that bear claws (n = 7). Quantitative analyses demonstrate that Notharctus tenebrosus possessed a grooming claw with a surprisingly well-developed apical tuft on its second pedal digit. The presence of a wide apical tuft on the pedal digit II of Notharctus tenebrosus may reflect intermediate morphology between a typical grooming claw and a nail, which is consistent with the recent hypothesis that loss of a grooming claw occurred in a clade containing adapiforms (e.g. Darwinius masillae) and anthropoids. However, a cladistic analysis including newly documented morphologies and thorough representation of characters acknowledged to have states constituting strepsirrhine, haplorhine, and anthropoid synapomorphies groups Notharctus tenebrosus and Darwinius masillae with extant strepsirrhines rather than haplorhines suggesting that the form of pedal digit II reflects substantial homoplasy during the course of early primate evolution.

  18. Mitochondrial Myopathy: A Rare Cause of Early-Onset Vocal Fold Atrophy

    Science.gov (United States)

    Kelly, Elizabeth A.; Bock, Jonathan M.; Peltier, Amanda C.; Oh, Shin J.; Garrett, C. Gaelyn

    2014-01-01

    Objectives We present the second published case of laryngeal involvement in mitochondrial myopathy. Methods A patient with laryngeal involvement of mitochondrial myopathy is presented, together with a literature review. Results A 41-year-old man presented with progressive breathy dysphonia. His brother had mitochondrial myopathy. Biopsy of the biceps muscle demonstrated cytochrome C oxidase–negative ragged blue fibers confirming mitochondrial myopathy. Videostroboscopy showed marked vocal fold atrophy, but subsequent injection laryngoplasty did not significantly improve the patient’s voice, despite improved postoperative glottic closure. Conclusions Mitochondrial myopathy should be considered in the differential diagnosis of severe early-onset vocal fold atrophy. PMID:23577570

  19. Genetic parameters for claw and leg health, foot and leg conformation, and locomotion in Danish Holsteins

    DEFF Research Database (Denmark)

    Laursen, M. V.; Boelling, D.; Mark, Thomas

    2009-01-01

    was defined as absence of hock infection, swollen hock, and bruising. The potential indicators were locomotion and foot and leg conformation, represented by rear leg side view, rear leg rear view, foot angle, and apparent hock quality and bone structure. The study was conducted using records from 429......,877 Danish Holstein cows in first lactation. Binary health traits were divided into 3 subcategories: claw health, leg health, and absence of all claw and leg disorders. Genetic (r(g)) and phenotypic correlations were estimated using a bivariate linear sire model and REML. Estimated heritabilities were 0.......01 for all 3 combined claw and leg health traits (on the observed binary scale), 0.09 for locomotion, 0.14 for rear leg rear view, 0.19 for rear leg side view, 0.13 for foot angle, 0.22 for apparent hock quality, and 0.27 for apparent bone structure. Heritabilities were 0.06 and 0.01 for claw health and leg...

  20. Autophagy-associated atrophy and metabolic remodeling of the mouse diaphragm after short-term intermittent hypoxia.

    Directory of Open Access Journals (Sweden)

    Christian Giordano

    Full Text Available Short-term intermittent hypoxia (IH is common in patients with acute respiratory disorders. Although prolonged exposure to hypoxia induces atrophy and increased fatigability of skeletal muscle, the response to short-term IH is less well known. We hypothesized that the diaphragm and limb muscles would adapt differently to short-term IH given that hypoxia stimulates ventilation and triggers a superimposed exercise stimulus in the diaphragm.We determined the structural, metabolic, and contractile properties of the mouse diaphragm after 4 days of IH (8 hours per day, 30 episodes per hour to a FiO2 nadir=6%, and compared responses in the diaphragm to a commonly studied reference limb muscle, the tibialis anterior. Outcome measures included muscle fiber size, assays of muscle proteolysis (calpain, ubiquitin-proteasome, and autophagy pathways, markers of oxidative stress and mitochondrial function, quantification of intramyocellular lipid and lipid metabolism genes, type I myosin heavy chain (MyHC expression, and in vitro contractile properties.After 4 days of IH, the diaphragm alone demonstrated significant atrophy (30% decrease of myofiber size together with increased LC3B-II protein (2.4-fold and mRNA markers of the autophagy pathway (LC3B, Gabarapl1, Bnip3, whereas active calpain and E3 ubiquitin ligases (MuRF1, atrogin-1 were unaffected in both muscles. Succinate dehydrogenase activity was significantly reduced by IH in both muscles. However, only the diaphragm exhibited increased intramyocellular lipid droplets (2.5-fold after IH, along with upregulation of genes linked to activated lipid metabolism. In addition, although the diaphragm showed evidence for acute fatigue immediately following IH, it underwent an adaptive fiber type switch toward slow type I MyHC-expressing fibers, associated with greater intrinsic endurance of the muscle during repetitive stimulation in vitro.Short-term IH induces preferential atrophy in the mouse diaphragm

  1. Progressive hemifacial atrophy with ciliary body atrophy and ocular hypotony

    Directory of Open Access Journals (Sweden)

    T Ashwini Kini

    2015-01-01

    Full Text Available Progressive hemifacial atrophy (PHA is a disease of unknown etiology affecting one-half of the face. Ocular involvement is uncommon. Atrophy of iris is rare, with only a few cases of partial atrophy being reported in the literature. We report a case of total atrophy of iris and ciliary body with associated ocular hypotony in a 16-year-old girl with PHA. We believe this is the first reported case of complete atrophy of iris and ciliary body in PHA. Ocular hypotony in PHA was thought to be due to intra-ocular inflammation. However in our case it appears to be secondary to severe atrophy of the ciliary body.

  2. Automatic assessment of volume asymmetries applied to hip abductor muscles in patients with hip arthroplasty

    Science.gov (United States)

    Klemt, Christian; Modat, Marc; Pichat, Jonas; Cardoso, M. J.; Henckel, Joahnn; Hart, Alister; Ourselin, Sebastien

    2015-03-01

    Metal-on-metal (MoM) hip arthroplasties have been utilised over the last 15 years to restore hip function for 1.5 million patients worldwide. Althoug widely used, this hip arthroplasty releases metal wear debris which lead to muscle atrophy. The degree of muscle wastage differs across patients ranging from mild to severe. The longterm outcomes for patients with MoM hip arthroplasty are reduced for increasing degrees of muscle atrophy, highlighting the need to automatically segment pathological muscles. The automated segmentation of pathological soft tissues is challenging as these lack distinct boundaries and morphologically differ across subjects. As a result, there is no method reported in the literature which has been successfully applied to automatically segment pathological muscles. We propose the first automated framework to delineate severely atrophied muscles by applying a novel automated segmentation propagation framework to patients with MoM hip arthroplasty. The proposed algorithm was used to automatically quantify muscle wastage in these patients.

  3. Age-Associated Loss of OPA1 in Muscle Impacts Muscle Mass, Metabolic Homeostasis, Systemic Inflammation, and Epithelial Senescence.

    Science.gov (United States)

    Tezze, Caterina; Romanello, Vanina; Desbats, Maria Andrea; Fadini, Gian Paolo; Albiero, Mattia; Favaro, Giulia; Ciciliot, Stefano; Soriano, Maria Eugenia; Morbidoni, Valeria; Cerqua, Cristina; Loefler, Stefan; Kern, Helmut; Franceschi, Claudio; Salvioli, Stefano; Conte, Maria; Blaauw, Bert; Zampieri, Sandra; Salviati, Leonardo; Scorrano, Luca; Sandri, Marco

    2017-06-06

    Mitochondrial dysfunction occurs during aging, but its impact on tissue senescence is unknown. Here, we find that sedentary but not active humans display an age-related decline in the mitochondrial protein, optic atrophy 1 (OPA1), that is associated with muscle loss. In adult mice, acute, muscle-specific deletion of Opa1 induces a precocious senescence phenotype and premature death. Conditional and inducible Opa1 deletion alters mitochondrial morphology and function but not DNA content. Mechanistically, the ablation of Opa1 leads to ER stress, which signals via the unfolded protein response (UPR) and FoxOs, inducing a catabolic program of muscle loss and systemic aging. Pharmacological inhibition of ER stress or muscle-specific deletion of FGF21 compensates for the loss of Opa1, restoring a normal metabolic state and preventing muscle atrophy and premature death. Thus, mitochondrial dysfunction in the muscle can trigger a cascade of signaling initiated at the ER that systemically affects general metabolism and aging. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  4. Prominent fatigue in spinal muscular atrophy and spinal and bulbar muscular atrophy: evidence of activity-dependent conduction block.

    Science.gov (United States)

    Noto, Yu-ichi; Misawa, Sonoko; Mori, Masahiro; Kawaguchi, Naoki; Kanai, Kazuaki; Shibuya, Kazumoto; Isose, Sagiri; Nasu, Saiko; Sekiguchi, Yukari; Beppu, Minako; Ohmori, Shigeki; Nakagawa, Masanori; Kuwabara, Satoshi

    2013-09-01

    To clarify whether patients with spinal muscular atrophy (SMA) or spinal and bulbar muscular atrophy (SBMA) suffer disabling muscle fatigue, and whether activity-dependent conduction block (ADCB) contributes to their fatigue. ADCB is usually caused by reduced safety factor for impulse transmission in demyelinating diseases, whereas markedly increased axonal branching associated with collateral sprouting may reduce the safety factor in chronic lower motor neuron disorders. We assessed the fatigue severity scale (FSS) in 22 patients with SMA/SBMA, and in 100 disease controls (multiple sclerosis, myasthenia gravis, chronic inflammatory demyelinating polyneuropathy (CIDP), and axonal neuropathy). We then performed stimulated-single fibre electromyography (s-SFEMG) in the extensor digitorum communis (EDC) muscle of 21 SMA/SBMA patients, 6 CIDP patients, and 10 normal subjects. The FSS score was the highest in SMA/SBMA patients [4.9 ± 1.1 (mean ± SD)], with 81% of them complaining of disabling fatigue, compared with normal controls (3.5 ± 1.0), whereas patients with multiple sclerosis (4.3 ± 1.6), myasthenia gravis (4.0 ± 1.6) or CIDP (4.3 ± 1.4) also showed higher FSS score. When 2000 stimuli were delivered at 20 Hz in s-SFEMG, conduction block of single motor axons developed in 46% of patients with SMA/SBMA, and 40% of CIDP patients, but in none of the normal controls. SMA/SBMA patients frequently suffer from disabling fatigue presumably caused by ADCB induced by voluntary activity. ADCB could be the mechanism for muscle fatigue in chronic lower motor neuron diseases. Copyright © 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  5. Schisandrae fructus enhances myogenic differentiation and inhibits atrophy through protein synthesis in human myotubes

    Directory of Open Access Journals (Sweden)

    Kim CH

    2016-05-01

    Full Text Available Cy Hyun Kim,1,2,* Jin-Hong Shin,1,3,* Sung Jun Hwang,1,2 Yung Hyun Choi,4 Dae-Seong Kim,1,3 Cheol Min Kim2,51Research Institute of Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, 2Center for Anti-Aging Industry, Pusan National University, Busan, 3Department of Neurology, Pusan National University Yangsan Hospital, Yangsan, 4Department of Biochemistry, Dong-eui University College of Korean Medicine, Busan, 5Department of Biomedical Informatics, Pusan National University School of Medicine, Yangsan, Republic of Korea*These authors contributed equally to this work Abstract: Schisandrae fructus (SF has recently been reported to increase skeletal muscle mass and inhibit atrophy in mice. We investigated the effect of SF extract on human myotube differentiation and its acting pathway. Various concentrations (0.1–10 µg/mL of SF extract were applied on human skeletal muscle cells in vitro. Myotube area and fusion index were measured to quantify myotube differentiation. The maximum effect was observed at 0.5 µg/mL of SF extract, enhancing differentiation up to 1.4-fold in fusion index and 1.6-fold in myotube area at 8 days after induction of differentiation compared to control. Phosphorylation of eukaryotic translation initiation factor 4E-binding protein 1 and 70 kDa ribosomal protein S6 kinase, which initiate translation as downstream of mammalian target of rapamycin pathway, was upregulated in early phases of differentiation after SF treatment. SF also attenuated dexamethasone-induced atrophy. In conclusion, we show that SF augments myogenic differentiation and attenuates atrophy by increasing protein synthesis through mammalian target of rapamycin/70 kDa ribosomal protein S6 kinase and eukaryotic translation initiation factor 4E-binding protein 1 signaling pathway in human myotubes. SF can be a useful natural dietary supplement in increasing skeletal muscle mass, especially in the aged

  6. Cardiac atrophy after bed rest and spaceflight

    Science.gov (United States)

    Perhonen, M. A.; Franco, F.; Lane, L. D.; Buckey, J. C.; Blomqvist, C. G.; Zerwekh, J. E.; Peshock, R. M.; Weatherall, P. T.; Levine, B. D.

    2001-01-01

    Cardiac muscle adapts well to changes in loading conditions. For example, left ventricular (LV) hypertrophy may be induced physiologically (via exercise training) or pathologically (via hypertension or valvular heart disease). If hypertension is treated, LV hypertrophy regresses, suggesting a sensitivity to LV work. However, whether physical inactivity in nonathletic populations causes adaptive changes in LV mass or even frank atrophy is not clear. We exposed previously sedentary men to 6 (n = 5) and 12 (n = 3) wk of horizontal bed rest. LV and right ventricular (RV) mass and end-diastolic volume were measured using cine magnetic resonance imaging (MRI) at 2, 6, and 12 wk of bed rest; five healthy men were also studied before and after at least 6 wk of routine daily activities as controls. In addition, four astronauts were exposed to the complete elimination of hydrostatic gradients during a spaceflight of 10 days. During bed rest, LV mass decreased by 8.0 +/- 2.2% (P = 0.005) after 6 wk with an additional atrophy of 7.6 +/- 2.3% in the subjects who remained in bed for 12 wk; there was no change in LV mass for the control subjects (153.0 +/- 12.2 vs. 153.4 +/- 12.1 g, P = 0.81). Mean wall thickness decreased (4 +/- 2.5%, P = 0.01) after 6 wk of bed rest associated with the decrease in LV mass, suggesting a physiological remodeling with respect to altered load. LV end-diastolic volume decreased by 14 +/- 1.7% (P = 0.002) after 2 wk of bed rest and changed minimally thereafter. After 6 wk of bed rest, RV free wall mass decreased by 10 +/- 2.7% (P = 0.06) and RV end-diastolic volume by 16 +/- 7.9% (P = 0.06). After spaceflight, LV mass decreased by 12 +/- 6.9% (P = 0.07). In conclusion, cardiac atrophy occurs during prolonged (6 wk) horizontal bed rest and may also occur after short-term spaceflight. We suggest that cardiac atrophy is due to a physiological adaptation to reduced myocardial load and work in real or simulated microgravity and demonstrates the plasticity

  7. [Proximal chemical composition and functional properties of fresh meat of crab claws (Homalaspis plana)].

    Science.gov (United States)

    Abugoch, L; Barrios, J; Guarda, A

    1996-12-01

    The research of alternative technological processes is being necessary in order to obtain a better utilization of hydrobiologic resources and food products, with higher added value. Crab (Homolaspis plana) is a crustacean found along the Chilean coast, whose flesh is exported as a frozen product. The resource crab is scantly studied in Chile and could became an excellent raw material for "delicatessen" products, with a high market value. The proximal composition, through the protein, fat, moisture and ashes content was determined. The non nitrogen extract was calculated by difference. The functional properties (water retention, emulsifying and gel-forming capacities) of fresh crab claws meat without additives were measured. The proximal composition for the claw meat was: 79,34 +/- 1.12% moisture, 16.75 +/- 1.29% protein, 1.86 +/- 0.11% ashes, 0.11 +/- 0.01 fat % and 1.93 +/- 1.07% N.N.E. In relation with the emulsifying capacity, claw meat was able to emulsify 2,259.03 +/- 73.04 g vegetal oil/g protein. The water retention was 154.49 +/- 6.85% representing the increase in mass percent; and the force of the gel formed in claw meat was 195.3 +/- 17.16 g-force x cm. According to these results, the claw crab is an attractive food, with a high protein and low fat content. Crab meat showed an excellent emulsifying capacity and water retention, so it can be used as a good raw material for the development of smearing products. In the case of gel-like products, further studies will be required, in order to optimize the conditions in which a stronger gel could be obtained.

  8. Spinal Muscular Atrophy: More than a Disease of Motor Neurons?

    Science.gov (United States)

    Nash, L A; Burns, J K; Chardon, J Warman; Kothary, R; Parks, R J

    2016-01-01

    Spinal muscular atrophy (SMA) is the most common genetically inherited neurodegenerative disease resulting in infant mortality. SMA is caused by genetic deletion or mutation in the survival of motor neuron 1 (SMN1) gene, which results in reduced levels of the survival of motor neuron (SMN) protein. SMN protein deficiency preferentially affects α- motor neurons, leading to their degeneration and subsequent atrophy of limb and trunk muscles, progressing to death in severe forms of the disease. More recent studies have shown that SMN protein depletion is detrimental to the functioning of other tissues including skeletal muscle, heart, autonomic and enteric nervous systems, metabolic/endocrine (e.g. pancreas), lymphatic, bone and reproductive system. In this review, we summarize studies discussing SMN protein's function in various cell and tissue types and their involvement in the context of SMA disease etiology. Taken together, these studies indicate that SMA is a multi-organ disease, which suggests that truly effective disease intervention may require body-wide correction of SMN protein levels. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  9. The effect of preventive trimming on weight bearing and force balance on the claws of dairy cattle

    NARCIS (Netherlands)

    Tol, van der P.P.J.; Beek, van der S.S.; Metz, J.H.M.; Noordhuizen-Stassen, E.N.; Back, E.; Braam, C.R.; Weijs, W.A.

    2004-01-01

    Claw disorders and lameness in dairy cattle are an increasing problem of the modern dairy industry. To prevent claw disorders from evolving from the subclinical to the clinical stage, trimming is the management practice most routinely applied. The goal of preventive trimming (Toussaint-Raven method)

  10. [Muscle biopsy in children: Usefulness in 2012].

    Science.gov (United States)

    Cuisset, J-M; Maurage, C-A; Carpentier, A; Briand, G; Thévenon, A; Rouaix, N; Vallée, L

    2013-01-01

    Muscle biopsy is a mainstay diagnostic tool for investigating neuromuscular disorders in children. We report the yield of pediatric muscle biopsy in a population of 415 children by a retrospective study of 419 biopsies performed between 1/01/2000 and 31/12/2009 in a neuropediatric department, including mitochondrial respiratory chain analysis for 87 children. Two hundred and fifty-five biopsies were from boys (61%) 164 from girls (39%). Their mean age at biopsy was 6.5years; 155 (37%) biopsies were obtained before the child was 5years old. Final histopathological diagnoses were: congenital myopathy (n=193, including 15 structural congenital myopathies); progressive muscular dystrophy (n=75 [18%] including 57 dystrophinopathies); congenital muscular dystrophy (n=17, including six primary merosinopathies); dermatomyositis (n=11); spinal muscular atrophy (n=9, including six atypical spinal muscular atrophies); metabolic myopathy (n=32, including 19 mitochondrial myopathies); encephalomyopathy (n=53 [13%], including 27 with a mitochondrial respiratory chain defect). Pathological diagnosis remained undetermined in 16 cases. In 184 patients (44%), the muscle biopsy revealed specific histopathological anomalies (dystrophic process; specific ultrastructural abnormalities; perifascicular atrophy; neurogenic atrophy; metabolic anomalies) enabling a precise etiological diagnosis. For 85% of progressive muscular dystrophies, the biopsy resulted in a genetic diagnosis after identification of the protein defect. In 15% of the congenital myopathies, histopathological anomalies focused attention on one or several genes. Concerning dystrophinopathies, quantification of dystrophin deficiency on the biopsy specimen contributed to the definition of the clinical phenotype: Duchenne, or Becker. In children with a myopathy, muscle biopsy is often indispensable to establish the etiological diagnosis. Based on the results from this series, muscle biopsy can provide a precise

  11. Development of a superconducting claw-pole motor

    International Nuclear Information System (INIS)

    Watanabe, E.; Kikukawa, K.; Satoh, Y.; Torii, S.

    2008-01-01

    We have developed and produced a superconducting claw-pole motor for a trial purpose as a method to make the best use of the characteristic of superconductivity without collector rings or rotating superconducting coils that need to be cryocooled, and made some examinations. The unique feature in this motor is to have the mechanism that supports the reaction magnetic force generated in the axial direction

  12. Iris reconstruction combined with iris-claw intraocular lens implantation for the management of iris-lens injured patients.

    Science.gov (United States)

    Hu, Shufang; Wang, Mingling; Xiao, Tianlin; Zhao, Zhenquan

    2016-03-01

    To study the efficiency and safety of iris reconstruction combined with iris-claw intraocular lens (IOL) implantation in the patients with iris-lens injuries. Retrospective, noncomparable consecutive case series study. Eleven patients (11 eyes) following iris-lens injuries underwent iris reconstructions combined with iris-claw IOL implantations. Clinical data, such as cause and time of injury, visual acuity (VA), iris and lens injuries, surgical intervention, follow-up period, corneal endothelial cell count, and optical coherence tomography, were collected. Uncorrected VA (UCVA) in all injured eyes before combined surgery was equal to or iris returned to its natural round shape or smaller pupil, and the iris-claw IOLs in the 11 eyes were well-positioned on the anterior surface of reconstructed iris. No complications occurred in those patients. Iris reconstruction combined with iris-claw IOL implantation is a safe and efficient procedure for an eye with iris-lens injury in the absence of capsular support.

  13. Effect of rubber flooring on group-housed sows' gait and claw and skin lesions.

    Science.gov (United States)

    Bos, E-J; van Riet, M M J; Maes, D; Millet, S; Ampe, B; Janssens, G P J; Tuyttens, F A M

    2016-05-01

    This study evaluated the influence of floor type on sow welfare in terms of lameness, claw lesions, and skin lesions. In a 2 × 3 factorial design, we have investigated the effect of rubber coverings on concrete floors and the effect of 3 levels of dietary zinc supplementation on locomotion and claw and skin lesions in group-housed sows. Six groups of 21 ± 4 hybrid sows were monitored during 3 successive reproductive cycles. The sows were group housed from d 28 after insemination (d 0) until 1 wk before expected farrowing date (d 108) in pens with either exposed concrete floors or concrete floors covered with rubber in part of the lying area and the fully slatted area. During each reproductive cycle, locomotion and skin lesions were assessed 4 times (d 28, 50, 108, and 140) and claw lesions were assessed twice (d 50 and 140). Results are given as least squares means ± SE. Locomotion and claw scores were given in millimeters, on analog scales of 150 and 160 mm, respectively. Here, we report on the effect of floor type, which did not interact with dietary zinc concentration ( > 0.10 for all variables). At move to group (d 28) and mid gestation (d 50), no differences between floor treatments were seen in locomotion ( > 0.10). At the end of gestation (d 108), sows housed on rubber flooring scored 9.9 ± 4.1 mm better on gait ( flooring at mid gestation (d 50). However, sows on rubber flooring scored worse for "vertical cracks in the wall horn" (difference of 3.4 ± 1.7 mm; = 0.04). At the end of lactation (d 140), both "white line" (difference of 2.9 ± 1 mm; = 0.02) and "claw length" (difference of 4.7 ± 1.4 mm; flooring. No differences for skin lesions were observed between floor treatments. The improved scores for gait toward the end of gestation and some types of claw disorders at mid gestation suggest that rubber flooring in group housing has a beneficial effect on the overall leg health of sows. The documented increase in vertical cracks in the wall horn at d

  14. Excitation-contraction coupling and mechano-sensitivity in denervated skeletal muscles

    Directory of Open Access Journals (Sweden)

    Fabio Francini

    2010-09-01

    Full Text Available Skeletal muscle atrophy can be defined as a wasting or decrease in muscle mass and muscle force generation owing lack of use, ageing, injury or disease. Thus, the etiology of atrophy can be different. Atrophy in denervated muscle is a consequence of two factors: 1 the complete lack of motoneuron activity inducing the deficiency of neurotransmitter release and 2 the muscles disuse. The balance of the muscular functions depends on extra- and intra-muscular signals. In the balance are involved the excitation-contraction coupling (ECC, local growth factors, Ca2+-dependent and independent intracellular signals, mechano-sensitivity and mechano-transduction that activate Ca2+-dependent signaling proteins and cytoskeleton- nucleus pathways to the nucleus, that regulate the gene expression. Moreover, retrograde signal from intracellular compartments and cytoskeleton to the sarcolemma are additional factors that regulate the muscle function. Proteolytic systems that operate in atrophic muscles progressively reduce the muscle protein content and so the sarcolemma, ECC and the force generation. In this review we will focus on the more relevant changes of the sarcolemma, excitation-contraction coupling, ECC and mechano-transduction evaluated by electrophysiological methods and observed from early- to long-term denervated skeletal muscles. This review put in particular evidence that long-term denervated muscle maintain a sub-population of fibers with ECC and contractile machinery able to be activated, albeit in lesser amounts, by electrical and mechanical stimulation. Accordingly, this provides a potential molecular explanation of the muscle recovery that occurs in response to rehabilitation strategy as transcutaneous electrical stimulation and passive stretching of denervated muscles, which wre developed as a result of empirical clinical observations.

  15. Effect of aerobic training in patients with spinal and bulbar muscular atrophy (Kennedy disease)

    DEFF Research Database (Denmark)

    Preisler, N; Andersen, G; Thøgersen, F

    2009-01-01

    ) or any of the other variables examined before and after training, and the patients with SBMA did not feel improvements in ADL. CONCLUSIONS: Frequent, moderate-intensity aerobic conditioning is of little beneficial effect in patients with spinal and bulbar muscular atrophy (SBMA). High levels of plasma......OBJECTIVE: We examined the effect of aerobic exercise in patients with spinal and bulbar muscular atrophy (SBMA). SBMA is caused by a defect androgen receptor. This defect causes motor neuron death, but considering the important function of androgens in muscle, it is possible that muscle damage...... measurements, lung function, plasma proteins, and hormones were evaluated before and after training. Evaluation of improvements in activities of daily living (ADL) was conducted after training. RESULTS: W(max) increased by 18%, and CS activity increased by 35%. There was no significant change in Vo(2max...

  16. cAMP signaling in skeletal muscle adaptation: hypertrophy, metabolism, and regeneration

    Science.gov (United States)

    Stewart, Randi

    2012-01-01

    Among organ systems, skeletal muscle is perhaps the most structurally specialized. The remarkable subcellular architecture of this tissue allows it to empower movement with instructions from motor neurons. Despite this high degree of specialization, skeletal muscle also has intrinsic signaling mechanisms that allow adaptation to long-term changes in demand and regeneration after acute damage. The second messenger adenosine 3′,5′-monophosphate (cAMP) not only elicits acute changes within myofibers during exercise but also contributes to myofiber size and metabolic phenotype in the long term. Strikingly, sustained activation of cAMP signaling leads to pronounced hypertrophic responses in skeletal myofibers through largely elusive molecular mechanisms. These pathways can promote hypertrophy and combat atrophy in animal models of disorders including muscular dystrophy, age-related atrophy, denervation injury, disuse atrophy, cancer cachexia, and sepsis. cAMP also participates in muscle development and regeneration mediated by muscle precursor cells; thus, downstream signaling pathways may potentially be harnessed to promote muscle regeneration in patients with acute damage or muscular dystrophy. In this review, we summarize studies implicating cAMP signaling in skeletal muscle adaptation. We also highlight ligands that induce cAMP signaling and downstream effectors that are promising pharmacological targets. PMID:22354781

  17. The complex of PAMAM-OH dendrimer with Angiotensin (1–7) prevented the disuse-induced skeletal muscle atrophy in mice

    Science.gov (United States)

    Márquez-Miranda, Valeria; Abrigo, Johanna; Rivera, Juan Carlos; Araya-Durán, Ingrid; Aravena, Javier; Simon, Felipe; Pacheco, Nicolás; González-Nilo, Fernando Danilo; Cabello-Verrugio, Claudio

    2017-01-01

    Angiotensin (1–7) (Ang-(1–7)) is a bioactive heptapeptide with a short half-life and has beneficial effects in several tissues – among them, skeletal muscle – by preventing muscle atrophy. Dendrimers are promising vehicles for the protection and transport of numerous bioactive molecules. This work explored the use of a neutral, non-cytotoxic hydroxyl-terminated poly(amidoamine) (PAMAM-OH) dendrimer as an Ang-(1–7) carrier. Bioinformatics analysis showed that the Ang-(1–7)-binding capacity of the dendrimer presented a 2:1 molar ratio. Molecular dynamics simulation analysis revealed the capacity of neutral PAMAM-OH to protect Ang-(1–7) and form stable complexes. The peptide coverage ability of the dendrimer was between ~50% and 65%. Furthermore, an electrophoretic mobility shift assay demonstrated that neutral PAMAM-OH effectively bonded peptides. Experimental results showed that the Ang-(1–7)/PAMAM-OH complex, but not Ang-(1–7) alone, had an anti-atrophic effect when administered intraperitoneally, as evaluated by muscle strength, fiber diameter, myofibrillar protein levels, and atrogin-1 and MuRF-1 expressions. The results of the Ang-(1–7)/PAMAM-OH complex being intraperitoneally injected were similar to the results obtained when Ang-(1–7) was systemically administered through mini-osmotic pumps. Together, the results suggest that Ang-(1–7) can be protected for PAMAM-OH when this complex is intraperitoneally injected. Therefore, the Ang-(1–7)/PAMAM-OH complex is an efficient delivery method for Ang-(1–7), since it improves the anti-atrophic activity of this peptide in skeletal muscle. PMID:28331320

  18. Quantitative MRI study of progressive cerebral atrophy in multiple system atrophy

    International Nuclear Information System (INIS)

    Konagaya, Masaaki; Matsuoka, Yukihiko; Konagaya, Yoko

    2002-01-01

    We investigated cerebral atrophy in multiple system atrophy (MSA) by quantitative analysis of MRI. The subjects were 28 patients with MSA (14 striato-nigral degeneration; SND, 14 olivo-ponto-cerebellar atrophy; OPCA. 106 MRI examinations were performed totally) and 85 normal persons for control. The ratios of the ventral pons to the infratentorial space in the sagittal section, the putamen, cerebrum, frontal lobe and parietal and occipital lobes to the intracranial space in the horizontal section, and the temporal lobe to the intracranial space in the coronal section were measured. In the early stage of the disease, OPCA showed significant atrophy of the ventral pons compared with SND, and conversely, SND demonstrated significantly smaller putamen than that in OPCA. According to the progression of the disease, the atrophy of these neural tissues progressed, which resulted in so significant differences between SND and OPCA. The cerebral atrophy was observed in 17 MSA patients. The atrophy of the frontal lobe was much frequent and prominent to that in the temporal lobe and parietal and occipital lobes. SND showed higher incidence of the cerebral atrophy than OPCA in the early stage of the disease. In long period follow-up cases, one case showed cerebral atrophy in earlier stage, and another case in late stage. We indicated the involvement of the cerebral hemispheres in MSA, especially the frontal lobe. (author)

  19. Quantitative MRI study of progressive cerebral atrophy in multiple system atrophy

    Energy Technology Data Exchange (ETDEWEB)

    Konagaya, Masaaki; Matsuoka, Yukihiko [Suzuka National Hospital, Suzuka, Mie (Japan); Konagaya, Yoko [JR Tokai General Hospital, Nagoya (Japan)

    2002-02-01

    We investigated cerebral atrophy in multiple system atrophy (MSA) by quantitative analysis of MRI. The subjects were 28 patients with MSA (14 striato-nigral degeneration; SND, 14 olivo-ponto-cerebellar atrophy; OPCA. 106 MRI examinations were performed totally) and 85 normal persons for control. The ratios of the ventral pons to the infratentorial space in the sagittal section, the putamen, cerebrum, frontal lobe and parietal and occipital lobes to the intracranial space in the horizontal section, and the temporal lobe to the intracranial space in the coronal section were measured. In the early stage of the disease, OPCA showed significant atrophy of the ventral pons compared with SND, and conversely, SND demonstrated significantly smaller putamen than that in OPCA. According to the progression of the disease, the atrophy of these neural tissues progressed, which resulted in so significant differences between SND and OPCA. The cerebral atrophy was observed in 17 MSA patients. The atrophy of the frontal lobe was much frequent and prominent to that in the temporal lobe and parietal and occipital lobes. SND showed higher incidence of the cerebral atrophy than OPCA in the early stage of the disease. In long period follow-up cases, one case showed cerebral atrophy in earlier stage, and another case in late stage. We indicated the involvement of the cerebral hemispheres in MSA, especially the frontal lobe. (author)

  20. Unilateral hypoplasia with contralateral hypertrophy of anterior belly of digastric muscle: a case report.

    Science.gov (United States)

    Ochoa-Escudero, Martin; Juliano, Amy F

    2016-10-01

    Anomalies of the anterior belly of the digastric muscle (DM) are uncommon. We present a case of hypoplasia of the anterior belly of the left DM with hypertrophy of the anterior belly of the contralateral DM. The importance of recognizing this finding is to differentiate hypoplasia of the anterior belly of the DM from denervation atrophy, and not to confuse contralateral hypertrophy with a submental mass or lymphadenopathy. In denervation atrophy of the anterior belly of the DM, associated atrophy of the ipsilateral mylohyoid muscle is present. Hypertrophy of the anterior belly of the contralateral DM can be differentiated from a submental mass or lymphadenopathy by recognizing its isodensity on computed tomography and isointensity on magnetic resonance imaging to other muscles, without abnormal contrast enhancement.

  1. Management and Level of Asian small-clawed otter (Aonyx cinereus Illinger, 1815 as Display Animal in Indonesia Conservation Institution

    Directory of Open Access Journals (Sweden)

    Ulfa Hansyari Ar-Rasyid

    2017-09-01

    Full Text Available Education and breeding become main reasons for asian small-clawed otter placement as display animal in zoo. Proper management is needed to maintain asian small-clawed otter welfare. This research objectives were to examine and assess asian small-clawed otter welfare in three Indonesia zoos. The study was conducted from December 2016 to February 2017 in Bandung Zoo, Ragunan Zoo and Ocean Dream Samudra Ancol. The methods of this research were literature review, interview and field observation. Data were analyzed using the suitability of management and animal welfare assessment. The result showed that there were three main management activities conducted at the three study locations, i.e., nutrition, housing, and health management. Bandung Zoo achieved the lowest score of asian small-clawed otter welfare (45,24% compared to Ragunan Zoo (62,24% and Ocean Dream Samudra (65,90%. Asian small-clawed otter welfare in three institutions were relatively low to fair category, this was due to the unfilled quality of food and water i.e.,  the type, amount, feeding frequency, diet and preparing of food; the unavailability of suitable and favorable environmental conditions; the care facilities provided could not ensure the health of animal; the appearance of abnormal behavior that affected the growth and breeding of animal; and animal had no freedom to behave as in their natural habitat. Keywords: animal display, animal welfare, Asian small-clawed otter, zoo 

  2. Effect of one stretch a week applied to the immobilized soleus muscle on rat muscle fiber morphology

    Directory of Open Access Journals (Sweden)

    Gomes A.R.S.

    2004-01-01

    Full Text Available We determined the effect of stretching applied once a week to the soleus muscle immobilized in the shortened position on muscle fiber morphology. Twenty-six male Wistar rats weighing 269 ± 26 g were divided into three groups. Group I, the left soleus was immobilized in the shortened position for 3 weeks; group II, the soleus was immobilized in the shortened position and stretched once a week for 3 weeks; group III, the soleus was submitted only to stretching once a week for 3 weeks. The medial part of the soleus muscle was frozen for histology and muscle fiber area evaluation and the lateral part was used for the determination of number and length of serial sarcomeres. Soleus muscle submitted only to immobilization showed a reduction in weight (44 ± 6%, P = 0.002, in serial sarcomere number (23 ± 15% and in cross-sectional area of the fibers (37 ± 31%, P < 0.001 compared to the contralateral muscles. The muscle that was immobilized and stretched showed less muscle fiber atrophy than the muscles only immobilized (P < 0.05. Surprisingly, in the muscles submitted only to stretching, fiber area was decreased compared to the contralateral muscle (2548 ± 659 vs 2961 ± 806 µm², respectively, P < 0.05. In conclusion, stretching applied once a week for 40 min to the soleus muscle immobilized in the shortened position was not sufficient to prevent the reduction of muscle weight and of serial sarcomere number, but provided significant protection against muscle fiber atrophy. In contrast, stretching normal muscles once a week caused a reduction in muscle fiber area.

  3. Pathogenesis-targeting therapeutics for spinal and bulbar muscular atrophy (SBMA).

    Science.gov (United States)

    Suzuki, Keisuke; Kastuno, Masahisa; Banno, Haruhiko; Sobue, Gen

    2009-08-01

    Spinal and bulbar muscular atrophy (SBMA) is an hereditary, adult-onset, lower motor neuron disease caused by an aberrant elongation of a trinucleotide CAG repeat, which encodes the polyglutamine tract, in the first exon of the androgen receptor (AR) gene. The main symptoms are slowly progressive muscle weakness and atrophy of bulbar, facial and limb muscles. The cardinal histopathological findings of SBMA are an extensive loss of lower motor neurons in the anterior horn of the spinal cord as well as in brainstem motor nuclei and intranuclear accumulations of mutant AR protein in the residual motor neurons. Androgen deprivation therapy rescues neuronal dysfunction in animal models of SBMA, suggesting that the molecular basis for motor neuron degeneration in this disorder is testosterone-dependent nuclear accumulation of the mutant AR. Suppression of disease progression by leuprorelin acetate has also been demonstrated in a phase 2 clinical trial. In addition, the clarification of pathophysiology leads to appearance of candidate drugs to treat this devastating disease: heat shock protein (HSP) inducer, Hsp90 inhibitor, and histone deacetylase inhibitor. Advances in basic and clinical research on SBMA are now paving the way for clinical application of pathogenesis-targeting therapeutics.

  4. Assessing the repeatability and reproducibility of the Leg Score: a Dutch Claw Health Scoring System for dairy cattle

    NARCIS (Netherlands)

    Holzhauer, M.; Middelesch, H.; Bartels, C.J.; Frankena, K.; Verhoeff, J.; Noordhuizen-Stassen, E.N.; Noordhuizen, J.P.T.M.

    2005-01-01

    The optimal moment for trimming the claws of all dairy cows in a herd was investigated by assessing the external rotation of the hind claws of individual cows relative to the spinal column. This leg score consisted of three independent descriptors: 1 (good/ normal), 2 (moderately deviant), and 3

  5. An algorithmic decomposition of claw-free graphs leading to an O(n^3) algorithm for the weighted stable set problem

    OpenAIRE

    Faenza, Y.; Oriolo, G.; Stauffer, G.

    2011-01-01

    We propose an algorithm for solving the maximum weighted stable set problem on claw-free graphs that runs in O(n^3)-time, drastically improving the previous best known complexity bound. This algorithm is based on a novel decomposition theorem for claw-free graphs, which is also intioduced in the present paper. Despite being weaker than the well-known structure result for claw-free graphs given by Chudnovsky and Seymour, our decomposition theorem is, on the other hand, algorithmic, i.e. it is ...

  6. Effects of alley and stall surfaces on indices of claw and leg health in dairy cattle housed in a free-stall barn.

    Science.gov (United States)

    Vokey, F J; Guard, C L; Erb, H N; Galton, D M

    2001-12-01

    A 15-wk 2 x 3 factorial trial in a university dairy herd compared the effects of two alley surfaces and three free-stall beds on indices of lameness. Alley surfaces were grooved concrete (Ct) or 1.9-cm-thick interlocking rubber mats (R). Stalls were deep sand (S), rubber mattresses (M), or concrete (C). Mattress and concrete stalls were bedded with sawdust. At wk 1 and 15, the hind claws and hocks of 120 primi- (n = 69) and multiparous (n = 51) cows were scored for lesions and three claw measurements (dorsal wall length, heel depth, and toe angle) were recorded. Rates of lateral and medial claw growth and wear were calculated by measuring the migration of a reference mark away from the coronet. Digital photographs of claw surfaces were used to rescore claw lesions. Clinical lameness was evaluated by assigning a locomotion score from 1 to 4 to each cow during wk 1, 5, 10, and 14. Digital dermatitis (present/not present) and interdigital dermatitis (mild, moderate, or severe) were recorded at wk 15. The number of days that cows spent in a hospital barn was recorded. Before assignment, cows were professionally foot trimmed, sorted by initial claw lesion score, and then randomized in consecutive blocks of three to stall treatments. Photograph scores were highly repeatable. Nonparametric statistical techniques were used for analyses of rank data. Claw lesion score increased significantly for all treatment groups except RC and RS; however, when early lactation cows were excluded, no differences were found between treatment groups. Hock scores increased significantly more for cows in CtC than in CtS or RS. Significantly more animals from RC spent more than 10 d in the hospital pen compared with RM and RS. Groups did not significantly differ for clinical lameness. Cows in RS and RC had significantly lower rates for lateral claw net growth than those in CtM. Having moderate or severe interdigital dermatitis at wk 15 was associated with greater increases in claw lesion score

  7. Strength training and aerobic exercise training for muscle disease.

    NARCIS (Netherlands)

    Voet, N.B.M.; Kooi, E.L. van der; Riphagen, I.I.; Lindeman, E.; Engelen, B.G.M. van; Geurts, A.C.H.

    2010-01-01

    BACKGROUND: Strength training or aerobic exercise programmes might optimise muscle and cardiorespiratory function and prevent additional disuse atrophy and deconditioning in people with a muscle disease. OBJECTIVES: To examine the safety and efficacy of strength training and aerobic exercise

  8. Proximal spinal muscular atrophy: current orthopedic perspective

    Directory of Open Access Journals (Sweden)

    Haaker G

    2013-11-01

    Full Text Available Gerrit Haaker, Albert Fujak Department of Orthopaedic Surgery, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany Abstract: 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. Keywords: spinal muscular atrophy, scoliosis, contractures, fractures, lung function, treatment, rehabilitation, surgery, ventilation, nutrition, perioperative management

  9. Renin-angiotensin system: an old player with novel functions in skeletal muscle.

    Science.gov (United States)

    Cabello-Verrugio, Claudio; Morales, María Gabriela; Rivera, Juan Carlos; Cabrera, Daniel; Simon, Felipe

    2015-05-01

    Skeletal muscle is a tissue that shows the most plasticity in the body; it can change in response to physiological and pathological stimuli. Among the diseases that affect skeletal muscle are myopathy-associated fibrosis, insulin resistance, and muscle atrophy. A common factor in these pathologies is the participation of the renin-angiotensin system (RAS). This system can be functionally separated into the classical and nonclassical RAS axis. The main components of the classical RAS pathway are angiotensin-converting enzyme (ACE), angiotensin II (Ang-II), and Ang-II receptors (AT receptors), whereas the nonclassical axis is composed of ACE2, angiotensin 1-7 [Ang (1-7)], and the Mas receptor. Hyperactivity of the classical axis in skeletal muscle has been associated with insulin resistance, atrophy, and fibrosis. In contrast, current evidence supports the action of the nonclassical RAS as a counter-regulator axis of the classical RAS pathway in skeletal muscle. In this review, we describe the mechanisms involved in the pathological effects of the classical RAS, advances in the use of pharmacological molecules to inhibit this axis, and the beneficial effects of stimulation of the nonclassical RAS pathway on insulin resistance, atrophy, and fibrosis in skeletal muscle. © 2015 Wiley Periodicals, Inc.

  10. Brain atrophy during aging

    International Nuclear Information System (INIS)

    Matsuzawa, Taiju; Yamada, Kenji; Yamada, Susumu; Ono, Shuichi; Takeda, Shunpei; Hatazawa, Jun; Ito, Masatoshi; Kubota, Kazuo

    1985-01-01

    Age-related brain atrophy was investigated in thousands of persons with no neurologic disturbances using X-CT and NMR-CT. Brain atrophy was minimal in 34-35 years old in both sexes, increased exponentially to the increasing age after 34-35 years, and probably resulted in dementia, such as vascular or multi-infarct dementia. Brain atrophy was significantly greater in men than in women at all ages. Brain volumes were maximal in 34-35 years old in both sexes with minimal individual differences which increased proportionally to the increasing age. Remarkable individual differences in the extent of brain atrophy (20 - 30 %) existed among aged subjects. Progression of brain atrophy was closely related to loss of mental activities independently of their ages. Our longitudinal study has revealed that the most important factors promoting brain atrophy during aging was the decrease in the cerebral blood flow. We have classified brain atrophy into sulcal and cisternal enlargement type (type I), ventricular enlargement type (type II) and mixed type (type III) according to the clinical study using NMR-CT. Brain atrophy of type I progresses significantly in almost all of the geriatric disorders. This type of brain atrophy progresses significantly in heavy smokers and drinkers. Therefore this type of brain atrophy might be caused by the decline in the blood flow in anterior and middle cerebral arteries. Brain atrophy of type II was caused by the disturbance of cerebrospinal fluid circulation after cerebral bleeding and subarachnoid bleeding. Brain atrophy of type III was seen in vascular dementia or multi-infarct dementia which was caused by loss of brain matter after multiple infarction, and was seen also in dementia of Alzheimer type in which degeneration of nerve cells results in brain atrophy. NMR-CT can easily detect small infarction (lacunae) and edematous lesions resulting from ischemia and hypertensive encephalopathy. (J.P.N.)

  11. Breeding biology of the eastern population of the Short-clawed Lark ...

    African Journals Online (AJOL)

    Breeding biology of the eastern population of the Short-clawed Lark in South Africa. ... courtship and copulation behaviour, the incubation period, description of the ... In contrast with the single-brooded western population, the eastern ...

  12. A prospective pilot study measuring muscle volumetric change in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Jenkins, Thomas M; Burness, Christine; Connolly, Daniel J; Rao, D Ganesh; Hoggard, Nigel; Mawson, Susan; McDermott, Christopher J; Wilkinson, Iain D; Shaw, Pamela J

    2013-09-01

    Our objective was to investigate the potential of muscle volume, measured with magnetic resonance (MR), as a biomarker to quantify disease progression in patients with amyotrophic lateral sclerosis (ALS). In this longitudinal pilot study, we first sought to determine the stability of volumetric muscle MR measurements in 11 control subjects at two time-points. We assessed feasibility of detecting atrophy in four patients with ALS, followed at three-month intervals for 12 months. Muscle power and MR volume were measured in thenar eminence (TEm), first dorsal interosseous (1DIO), tibialis anterior (TA) and tongue. Changes over time were assessed using linear regression models and t-tests. Results demonstrated that, in controls, no volumetric MR changes were seen (mean volume variation in all muscles 0.1). In patients, between-subject heterogeneity was identified. Trends for volume loss were found in TEm (mean, - 26.84%, p = 0.056) and TA (- 8.29%, p = 0.077), but not in 1DIO (- 18.47%, p = 0.121) or tongue (< 5%, p = 0.367). In conclusion, volumetric muscle MR appears a stable measure in controls, and progressive volume loss was demonstrable in individuals with ALS in whom clinical weakness progressed. In this small study, subclinical atrophy was not demonstrable using muscle MR. Clinico-radiological discordance between muscle weakness and MR atrophy could reflect a contribution of upper motor neuron pathology.

  13. Iris-claw intraocular lenses to correct aphakia in the absence of capsule support.

    Science.gov (United States)

    De Silva, Samantha R; Arun, Kikkeri; Anandan, Maghizh; Glover, Nicholas; Patel, Chetan K; Rosen, Paul

    2011-09-01

    To evaluate the indications, postoperative visual efficacy, and complication rate after intraocular implantation of an iris-claw aphakic intraocular lens (IOL). Oxford Eye Hospital, Oxford, United Kingdom. Case series. This chart review comprised eyes with no capsule support that had anterior iris-fixation IOL implantation for aphakia between 2001 and 2009. The study comprised 116 eyes (104 patients). Iris-claw IOLs were inserted during primary lens surgery in 18 eyes (15.5%), during an IOL exchange procedure for dislocated posterior chamber IOLs in 19 eyes (16.4%), and as a secondary procedure in 79 eyes (68.1%). The mean follow-up was 22.4 months (range 3 to 79 months). The final corrected distance visual acuity (CDVA) was 6/12 or better in 68.9% of all eyes and in 47 of 53 eyes (88.7%) with no preoperative comorbidity. Complications included wound leak requiring resuturing in 2.6% of eyes, postoperative intraocular pressure rise in 9.5% of eyes (glaucoma escalation 0.8%), and cystoid macular edema in 7.7% of eyes (0.8% chronic). Iris-claw IOL subluxation occurred in 6.0% of eyes from 5 days to 60 months postoperatively; all the IOLs were repositioned. Corneal decompensation occurred in 1.7% of eyes; 0.8% had retinal detachments. Iris-claw IOL implantation for aphakia gave a good visual outcome and can be used for a wide range of indications. Postoperative complication rates were comparable to, if not better than, those with conventional anterior chamber IOLs. Correct implantation technique is critical in avoiding postoperative IOL subluxation. Copyright © 2011 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

  14. Effect of claw horn lesion type and severity at the time of treatment on outcome of lameness in dairy cows.

    Science.gov (United States)

    Miguel-Pacheco, Giuliana G; Thomas, Heather J; Huxley, Jonathan N; Newsome, Reuben F; Kaler, Jasmeet

    2017-07-01

    Prompt diagnosis and treatment of claw horn lesions in cattle affects the likelihood of recovery; however, it is unknown if the type of lesion influences the likelihood of recovery. The aim of this study was to investigate whether the type, severity and frequency of claw horn lesions in newly lame cows (lame for no more than 2 weeks) at the time of corrective foot trimming affects the probability of recovery from lameness after treatment. The images of 112 feet (224 claws) from newly lame cows (n=112; lame in only one hind foot), which were treated with a standardised therapeutic hoof trim only, were used to score claw horn lesions (sole ulcer, sole haemorrhage, white line haemorrhage or white line separation). Most cows (n=107/112; 95.5%) were classified as mildly lame at the time of treatment. The proportion of cows that recovered 2 weeks after therapeutic hoof trimming was 88/112 (78.6%). Results of a multilevel logistic regression model indicated that severely lame cows were less likely to recover than those that were mildly lame (odds ratio, OR, 0.16; P=0.04). White line haemorrhage had a significant negative impact on the likelihood of recovery from lameness (OR 0.14; P>0.01); however, recovery of cows with white line haemorrhage was positively associated with the length of the lesion (OR 1.05; P=0.03). This latter finding may be associated with the severity of the lesion, since mild claw horn lesions affected a significantly larger area of the claw than more severe lesions. The length and type of claw horn lesion were associated with recovery from lameness. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Muscle structure and stiffness assessment after botulinum toxin type A injection. A systematic review.

    Science.gov (United States)

    Mathevon, L; Michel, F; Decavel, P; Fernandez, B; Parratte, B; Calmels, P

    2015-12-01

    Botulinum toxin type A manages spasticity disorders in neurological central diseases. Some studies have reported that it might induce muscle changes. We present a literature review abiding by the PRISMA statement guidelines. The purpose was to explore the structural and passive biomechanical muscle properties after botulinum toxin type A injections in healthy and spastic limb muscles, on animals and humans, as well as methods for evaluating these properties. We searched the PubMed and Cochrane Library databases using the following keywords: "Botulinum toxin" AND ("muscle structure" OR "muscle atrophy") and, "Botulinum toxin" AND "muscle elasticity". From the 228 initially identified articles, 21 articles were included. Histological analyses were performed, especially on animals. A neurogenic atrophy systematically occurred. In humans, one year after a single injection, the histological recovery remained incomplete. Furthermore, 2D ultrasound analyses showed a reduction of the gastrocnemius thickness and pennation angle. MRI volumetric analysis evidenced muscular atrophy six months or one year after a single injection. Passive muscle stiffness depends on these structural changes. On the short term, the biomechanical analysis showed an elastic modulus increase in animals whereas no change was recorded in humans. On the short term, ultrasound elastography imaging showed a decreased elastic modulus. To date, few data are available, but all show a structural and mechanical muscle impact post injections, specifically muscle atrophy which can linger over time. Further studies are necessary to validate this element, and the possibility of change must be taken into account particularly with repeated injections. Thus, in clinical practice, 2D ultrasound and ultrasound elastography are two non-invasive techniques that will help physicians to develop an efficient long term monitoring. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  16. Isolated atrophy of the abductor digiti quinti in patients with rheumatoid arthritis

    Energy Technology Data Exchange (ETDEWEB)

    Andrade Fernandes de Mello, Ricardo; Garcia Rondina, Ronaldo; Valim, Valeria; Santos Belisario, Stephano; Batista, Elton Francisco [Universidade Federal do Espirito Santo, Department of Internal Medicine, Vitoria, ES (Brazil); Burgomeister Lourenco, Rafael [HUCAM/UFES, Division of Medical Imaging, Vitoria, ES (Brazil); Duque, Ruben Horst [HUCAM/UFES, Division of Rheumatology, Vitoria, ES (Brazil)

    2017-12-15

    We aim to discuss the association of isolated atrophy of the abductor digiti quinti muscle in patients with rheumatoid arthritis as well as review the anatomy and imaging findings of this condition on MRI. A consecutive series of 55 patients diagnosed with rheumatoid arthritis according to the 2010 ACR/EULAR classification criteria were recruited. MRI of the clinically dominant feet was performed using a 1.5-T scanner. The study population was predominantly female (94.5%), and the age range was 31-79 years (mean 57.5 ± 11). A total of 55 ankles were examined by MRI, and 20 patients (36.3%), all females, showed abductor digiti quinti denervation signs. Seven patients demonstrated severe fatty atrophy of the abductor digiti quinti, corresponding to Goutallier grade 4, 2 patients showed moderate fatty atrophy (Goutallier grade 3), and the remaining 11 patients showed less than 50% fatty atrophy, corresponding to a Goutallier grade 2. Substantial agreement was found for both intra- and interobserver agreement regarding the Goutallier grading system. Prevalence of signs of abductor digiti quinti denervation on MRI was high in the studied population, suggesting that rheumatoid arthritis may be associated with inferior calcaneal nerve compression. (orig.)

  17. Isolated atrophy of the abductor digiti quinti in patients with rheumatoid arthritis

    International Nuclear Information System (INIS)

    Andrade Fernandes de Mello, Ricardo; Garcia Rondina, Ronaldo; Valim, Valeria; Santos Belisario, Stephano; Batista, Elton Francisco; Burgomeister Lourenco, Rafael; Duque, Ruben Horst

    2017-01-01

    We aim to discuss the association of isolated atrophy of the abductor digiti quinti muscle in patients with rheumatoid arthritis as well as review the anatomy and imaging findings of this condition on MRI. A consecutive series of 55 patients diagnosed with rheumatoid arthritis according to the 2010 ACR/EULAR classification criteria were recruited. MRI of the clinically dominant feet was performed using a 1.5-T scanner. The study population was predominantly female (94.5%), and the age range was 31-79 years (mean 57.5 ± 11). A total of 55 ankles were examined by MRI, and 20 patients (36.3%), all females, showed abductor digiti quinti denervation signs. Seven patients demonstrated severe fatty atrophy of the abductor digiti quinti, corresponding to Goutallier grade 4, 2 patients showed moderate fatty atrophy (Goutallier grade 3), and the remaining 11 patients showed less than 50% fatty atrophy, corresponding to a Goutallier grade 2. Substantial agreement was found for both intra- and interobserver agreement regarding the Goutallier grading system. Prevalence of signs of abductor digiti quinti denervation on MRI was high in the studied population, suggesting that rheumatoid arthritis may be associated with inferior calcaneal nerve compression. (orig.)

  18. Strength training and aerobic exercise training for muscle disease

    NARCIS (Netherlands)

    Voet, N.B.M.; Kooi, E.L. van der; Riphagen, I.I.; Lindeman, E.; Engelen, B.G.M. van; Geurts, A.C.H.

    2013-01-01

    BACKGROUND: Strength training or aerobic exercise programmes might optimise muscle and cardiorespiratory function and prevent additional disuse atrophy and deconditioning in people with a muscle disease. This is an update of a review first published in 2004. OBJECTIVES: To examine the safety and

  19. Optimization Design and Performance Analysis of a PM Brushless Rotor Claw Pole Motor with FEM

    Directory of Open Access Journals (Sweden)

    Zhenyang Zhang

    2016-07-01

    Full Text Available A new type of permanent magnet (PM brushless claw pole motor (CPM with soft magnetic composite (SMC core is designed and analyzed in this paper. The PMs are mounted on the claw pole surface, and the three-phase stator windings are fed by variable-frequency three-phase AC currents. The advantages of the proposed CPM are that the slip rings on the rotor are cast off and it can achieve the efficiency improvement and higher power density. The effects of the claw-pole structure parameters, the air-gap length, and the PM thinner parameter of the proposed CPM on the output torque are investigated by using three-dimensional time-stepping finite element method (3D TS-FEM. The optimal rotor structure of the proposed CPM is obtained by using the response surface methodology (RSM and the particle swarm optimization (PSO method and the comparison of full-load performances of the proposed CPM with different material cores (SMC and silicon steel is analyzed.

  20. More than a bystander: the contributions of intrinsic skeletal muscle defects in motor neuron diseases.

    Science.gov (United States)

    Boyer, Justin G; Ferrier, Andrew; Kothary, Rashmi

    2013-12-18

    Spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS), and spinal-bulbar muscular atrophy (SBMA) are devastating diseases characterized by the degeneration of motor neurons. Although the molecular causes underlying these diseases differ, recent findings have highlighted the contribution of intrinsic skeletal muscle defects in motor neuron diseases. The use of cell culture and animal models has led to the important finding that muscle defects occur prior to and independently of motor neuron degeneration in motor neuron diseases. In SMA for instance, the muscle specific requirements of the SMA disease-causing gene have been demonstrated by a series of genetic rescue experiments in SMA models. Conditional ALS mouse models expressing a muscle specific mutant SOD1 gene develop atrophy and muscle degeneration in the absence of motor neuron pathology. Treating SBMA mice by over-expressing IGF-1 in a skeletal muscle-specific manner attenuates disease severity and improves motor neuron pathology. In the present review, we provide an in depth description of muscle intrinsic defects, and discuss how they impact muscle function in these diseases. Furthermore, we discuss muscle-specific therapeutic strategies used to treat animal models of SMA, ALS, and SBMA. The study of intrinsic skeletal muscle defects is crucial for the understanding of the pathophysiology of these diseases and will open new therapeutic options for the treatment of motor neuron diseases.

  1. Skeletal muscle myostatin mRNA expression is fiber-type specific and increases during hindlimb unloading

    Science.gov (United States)

    Carlson, C. J.; Booth, F. W.; Gordon, S. E.

    1999-01-01

    Transgenic mice lacking a functional myostatin (MSTN) gene demonstrate greater skeletal muscle mass resulting from muscle fiber hypertrophy and hyperplasia (McPherron, A. C., A. M. Lawler, and S. -J. Lee. Nature 387: 83-90, 1997). Therefore, we hypothesized that, in normal mice, MSTN may act as a negative regulator of muscle mass. Specifically, we hypothesized that the predominately slow (type I) soleus muscle, which demonstrates greater atrophy than the fast (type II) gastrocnemius-plantaris complex (Gast/PLT), would show more elevation in MSTN mRNA abundance during hindlimb unloading (HU). Surprisingly, MSTN mRNA was not detectable in weight-bearing or HU soleus muscle, which atrophied 42% by the 7th day of HU in female ICR mice. In contrast, MSTN mRNA was present in weight-bearing Gast/PLT muscle and was significantly elevated (67%) at 1 day but not at 3 or 7 days of HU. However, the Gast/PLT muscle had only atrophied 17% by the 7th day of HU. Because the soleus is composed only of type I and IIa fibers, whereas the Gast/PLT expresses type IId/x and IIb in addition to type I and IIa, it was necessary to perform a more careful analysis of the relationship between MSTN mRNA levels and myosin heavy-chain (MHC) isoform expression (as a marker of fiber type). A significant correlation (r = 0.725, P < 0. 0005) was noted between the percentage of MHC isoform IIb expression and MSTN mRNA abundance in several muscles of the mouse hindlimb. These results indicate that MSTN expression is not strongly associated with muscle atrophy induced by HU; however, it is strongly associated with MHC isoform IIb expression in normal muscle.

  2. F-BOX proteins in cancer cachexia and muscle wasting: Emerging regulators and therapeutic opportunities.

    Science.gov (United States)

    Sukari, Ammar; Muqbil, Irfana; Mohammad, Ramzi M; Philip, Philip A; Azmi, Asfar S

    2016-02-01

    Cancer cachexia is a debilitating metabolic syndrome accounting for fatigue, an impairment of normal activities, loss of muscle mass associated with body weight loss eventually leading to death in majority of patients with advanced disease. Cachexia patients undergoing skeletal muscle atrophy show consistent activation of the SCF ubiquitin ligase (F-BOX) family member Atrogin-1 (also known as MAFBx/FBXO32) alongside the activation of the muscle ring finger protein1 (MuRF1). Other lesser known F-BOX family members are also emerging as key players supporting muscle wasting pathways. Recent work highlights a spectrum of different cancer signaling mechanisms impacting F-BOX family members that feed forward muscle atrophy related genes during cachexia. These novel players provide unique opportunities to block cachexia induced skeletal muscle atrophy by therapeutically targeting the SCF protein ligases. Conversely, strategies that induce the production of proteins may be helpful to counter the effects of these F-BOX proteins. Through this review, we bring forward some novel targets that promote atrogin-1 signaling in cachexia and muscle wasting and highlight newer therapeutic opportunities that can help in the better management of patients with this devastating and fatal disorder. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Muscle sonography in six patients with hereditary inclusion body myopathy

    International Nuclear Information System (INIS)

    Adler, Ronald S.; Garolfalo, Giovanna; Paget, Stephen; Kagen, Lawrence

    2008-01-01

    To evaluate the morphological changes of muscle with sonography in six patients affected by hereditary inclusion body myopathy (HIBM). We studied a group of six Persian Jews diagnosed with HIBM. All were homozygous for the GNE mutation M712T. Ultrasonographic examinations of the quadriceps femoris and hamstring muscle groups were performed. A follow-up ultrasound examination was performed, after an interval of 3 years, in four of these patients. Muscles were assessed subjectively as to echogenicity, determined by gray-scale assessment, and loss of normal muscle morphology. Power Doppler sonography (PDS) was used to assess vascularity. A sonographic finding of central atrophy and peripheral sparing resulting in a target-like appearance was noted in the hamstring compartment of all six patients. The quadriceps compartment also showed involvement of the rectus femoris of all patients, which, in some cases, was the only muscle involved in the quadriceps. Vascularity was markedly reduced in the affected areas, with blood flow demonstrated in the peripherally spared areas. The severity of atrophy increased with disease duration. In this case series, we describe a new sonographic finding as well as document progression of HIBM disease, which has generally been described as quadriceps sparing. The myopathic target lesion, as well as isolated rectus femoris atrophy, may provide a useful adjunct to disease diagnosis. (orig.)

  4. Speculations on colonizing success of the African clawed frog ...

    African Journals Online (AJOL)

    1991-12-12

    Dec 12, 1991 ... Robinson. Ann. Durban Mus. 1: 167-170. SMITH, J.L.B. 1961. Fishes of the family Apogonidae of the western Indian Ocean and the Red Sea.lchlhyol. .... J. Herp. 12: 391-396. BAIRD, T. 1983. Influence of social and predatory stimulus on the air-breathing behavior of the African clawed frog,. Xenopus laevis.

  5. CLAWS. Beam background monitoring in the commissioning of SuperKEKB

    Energy Technology Data Exchange (ETDEWEB)

    Gabriel, Miroslav; Windel, Hendrik; Kolk, Naomi van der; Simon, Frank [Max Planck Institute for Physics (Germany)

    2016-07-01

    The background levels, in particular those originating from the continuous injection to maximize luminosity, are a concern for the inner vertex detector of Belle-II at the SuperKEKB accelerator. To better understand this background, and in particular its time dependence, dedicated measurements will be made during the commissioning phase of the accelerator, scheduled to begin in February 2016. One of the detectors for these measurements, CLAWS, is based on scintillators coupled to SiPMs which were originally developed for timing measurements of hadronic showers in the CALICE calorimeters. The data acquisition is based on digitizers with very deep buffers allowing the continuous recording of more than 1000 revolutions of the accelerator to provide a detailed analysis of the evolution of the background levels after injection. In this contribution, we present the overall CLAWS setup, the technical solutions adopted for the data acquisition and analysis, and discuss the performance of the detector elements.

  6. The Regulation of Muscle Mass by Endogenous Glucocorticoids

    Directory of Open Access Journals (Sweden)

    Daniel L Marks

    2015-02-01

    Full Text Available Glucocorticoids are highly conserved fundamental regulators of energy homeostasis. In response to stress in the form of perceived danger or acute inflammation, glucocorticoids are released from the adrenal gland, rapidly mobilizing energy from carbohydrate, fat and protein stores. In the case of inflammation, mobilized protein is critical for the rapid synthesis of acute phase reactants and an efficient immune response to infection. While adaptive in response to infection, chronic mobilization can lead to a p rofound depletion of energy stores. Skeletal muscle represents the major body store of protein, and can become substantially atrophied under conditions of chronic inflammation. Glucocorticoids elicit the atrophy of muscle by increasing the rate of protein degradation by the ubiquitin-proteasome system and autophagy lysosome system. Protein synthesis is also suppressed at the level of translational initiation, preventing the production of new myofibrillar protein. Glucocorticoids also antagonize the action of anabolic regulators such as insulin further exacerbating the loss of protein and muscle mass. The loss of muscle mass in the context of chronic disease is a key feature of cachexia and contributes substantially to morbidity and mortality. A growing body of evidence demonstrates that glucocorticoid signaling is a common mediator of wasting, irrespective of the underlying initiator or disease state. This review will highlight fundamental mechanisms of glucocorticoid signaling and detail the mechanisms of glucocorticoid-induced muscle atrophy. Additionally, the evidence for glucocorticoids as a driver of muscle wasting in numerous disease states will be discussed. Given the burden of wasting diseases and the nodal nature of glucocorticoid signaling, effective anti-glucocorticoid therapy would be a valuable clinical tool. Therefore, the progress and potential pitfalls in the development of glucocorticoid antagonists for muscle wasting will

  7. Structural Changes of Lumbar Muscles in Non-specific Low Back Pain: A Systematic Review.

    Science.gov (United States)

    Goubert, Dorien; Oosterwijck, Jessica Van; Meeus, Mira; Danneels, Lieven

    2016-01-01

    Lumbar muscle dysfunction due to pain might be related to altered lumbar muscle structure. Macroscopically, muscle degeneration in low back pain (LBP) is characterized by a decrease in cross-sectional area and an increase in fat infiltration in the lumbar paraspinal muscles. In addition microscopic changes, such as changes in fiber distribution, might occur. Inconsistencies in results from different studies make it difficult to draw firm conclusions on which structural changes are present in the different types of non-specific LBP. Insights regarding structural muscle alterations in LBP are, however, important for prevention and treatment of non-specific LBP. The goal of this article is to review which macro- and/or microscopic structural alterations of the lumbar muscles occur in case of non-specific chronic low back pain (CLBP), recurrent low back pain (RLBP), and acute low back pain (ALBP). Systematic review. All selected studies were case-control studies. A systematic literature search was conducted in the databases PubMed and Web of Science. Only full texts of original studies regarding structural alterations (atrophy, fat infiltration, and fiber type distribution) in lumbar muscles of patients with non-specific LBP compared to healthy controls were included. All included articles were scored on methodological quality. Fifteen studies were found eligible after screening title, abstract, and full text for inclusion and exclusion criteria. In CLBP, moderate evidence of atrophy was found in the multifidus; whereas, results in the paraspinal and the erector spinae muscle remain inconclusive. Also moderate evidence occurred in RLBP and ALBP, where no atrophy was shown in any lumbar muscle. Conflicting results were seen in undefined LBP groups. Results concerning fat infiltration were inconsistent in CLBP. On the other hand, there is moderate evidence in RLBP that fat infiltration does not occur, although a larger muscle fat index was found in the erector spinae

  8. STUDIES ON THE WHITE-CLAWED CRAYFISH (AUSTROPOTAMOBIUS PALLIPES ASSOCIATED WITH MUDDY HABITATS

    Directory of Open Access Journals (Sweden)

    HOLDICH D. M.

    2006-01-01

    Full Text Available The white-clawed crayfish, Austropotamobius pallipes, is usually found associated with stony habitats containing obvious refuges in the form of gaps between and under rocks, macrophytes and marginal tree roots, particularly in streams and lakes with clear water and little marginal mud. If the banks are composed of suitable material, then they may also construct and live in burrows. However, the white-clawed crayfish is also found to be abundant in streams, rivers, canals and millraces with deep, anoxic mud and with very little aquatic vegetation. Foraging on the surface of mud may be the only way they can obtain sufficient food in the form of macroinvertebrates and decaying plant matter. Where do crayfish live in this restricted habitat? Dewatering such waterways for essential engineering works, such as desilting, bridge and weir repairs, bank reinforcements, and maintenance of outfalls can provide an excellent opportunity to study the available habitat and the crayfish populations, in addition good estimates of population size and age class distribution can be obtained, although, as with other methods, juveniles tend to be underrepresented. A number of case studies will be given to illustrate the fact that white-clawed crayfish are able to colonize muddy habitats in some numbers. The value of retaining trees with their roots hanging into waterways as a refuge for both crayfish and small fish is highlighted.

  9. Angiotensin II induced catabolic effect and muscle atrophy are redox dependent

    Science.gov (United States)

    Semprun-Prieto, Laura C.; Sukhanov, Sergiy; Yoshida, Tadashi; Rezk, Bashir M.; Gonzalez-Villalobos, Romer A.; Vaughn, Charlotte; Tabony, A. Michael; Delafontaine, Patrice

    2011-01-01

    Angiotensin II (Ang II) causes skeletal muscle wasting via an increase in muscle catabolism. To determine whether the wasting effects of Ang II were related to its ability to increase NADPH oxidase-derived reactive oxygen species (ROS) we infused wild-type C57BL/6J or p47phox−/− mice with vehicle or Ang II for 7 days. Superoxide production was increased 2.4 fold in the skeletal muscle of Ang II infused mice, and this increase was prevented in p47phox−/− mice. Apocynin treatment prevented Ang II-induced superoxide production in skeletal muscle, consistent with Ang II increasing NADPH oxidase derived ROS. Ang II induced loss of body and skeletal muscle weight in C57BL/6J mice, whereas the reduction was significantly attenuated in p47phox−/− animals. The reduction of skeletal muscle weight caused by Ang II was associated with an increase of proteasome activity, and this increase was completely prevented in the skeletal muscle of p47phox−/− mice. In conclusion, Ang II-induced skeletal muscle wasting is in part dependent on NADPH oxidase derived ROS. PMID:21570954

  10. Locomotion and claw disorders in Norwegian dairy cows housed in freestalls with slatted concrete, solid concrete, or solid rubber flooring in the alleys.

    Science.gov (United States)

    Fjeldaas, T; Sogstad, A M; Osterås, O

    2011-03-01

    This study was part of a cross-sectional project on freestall housing, and the aim was to compare locomotion and claw disorders in freestall dairy cattle herds with slatted concrete, solid concrete, or solid rubber flooring in the alleys. The final population for studying claw disorders consisted of 66 dairy herds with 2,709 dry or lactating cows, whereas the population for studying locomotion consisted of 54 herds with 2,216 cows. All herds used Norwegian Red as the main breed. The herds were visited by 15 trained claw trimmers one time during the period from the beginning of February to summer let-out onto pasture in 2008. The trimmers assessed locomotion scores (LocS) of all cows before trimming. At trimming, claw disorders were diagnosed and recorded in the Norwegian Claw Health Card. Estimates describing locomotion and claw disorders in the hind feet were identified by use of multivariable models fit with LocS and each claw disorder as dependent variables, respectively. Herd nested within claw trimmer was included in the model as random effects. The odds ratio (OR) of having LocS >2 and LocS >3 was 1.9 and 2.1, respectively, on slatted concrete compared with solid concrete. Fewer cases of dermatitis were found on slatted than solid concrete (OR=0.70) and a tendency was observed for fewer heel horn erosions on slatted concrete than solid rubber (OR=0.47). Hemorrhages of the white line and sole were more prevalent in herds housed on slatted and solid concrete than in those housed on solid rubber (OR=2.6 and OR=2.1, respectively). White line fissures were also more prevalent in herds housed on slatted and solid concrete than in those housed on solid rubber (OR=2.1 and OR=2.0, respectively). Double soles were more prevalent on solid concrete than solid rubber (OR=4.4). However, sole ulcers were less prevalent in herds with slatted and solid concrete than solid rubber (OR=0.39 and OR=0.53, respectively). Fewer corkscrewed claws were found on slatted concrete than

  11. Supplementation of Carrot (Daucus carrota as Natural Source of Beta-carotene prepared by Several Methods in Feed to Increase Blue Colour of Freshwater Crayfish Red Claw (Cherax quadricarinatus

    Directory of Open Access Journals (Sweden)

    Woro H. Satyantini

    2012-02-01

    Full Text Available Red claw (Cherax quadricarinatus is one kind of freshwater crayfish that can cultured as consumption or ornamental fish commodities.  The colour of body was important character for performance of red claw as ornamental fish commodity.  Red claw with blue body colour is more expensive than brown.  The purpose of  this experiment was to know the influence addition of carrot with several methods in feed on blue colour  of freshwater crayfish red claw and which was the best preparation method to increase blue colour of freshwater crayfish red claw. The experiment used Completely Randomized Design with four treatments: A (control, B (extract, C (juice and D (shreeded of carrot with 45 ppm dose and five time replicates.  Data was analysed with Kruskal-Wallis and continued with Z test. Result of the experiment was showed that addition of carrot as natural source of beta-carotene with several preparation in feed increase significantly (P Keywords: freshwater crayfish, colour of red claw, carrot, beta-carotene   ABSTRAK Red claw (Cherax quadricarinatus adalah salah satu jenis lobster air tawar yang dapat dibudidayakan sebagai komoditas konsumsi maupun hias.  Sebagai komoditas ikan hias, warna tubuh merupakan karakter penting untuk menunjang penampilan red claw.  Red claw ukuran konsumsi yang memiliki warna biru akan memiliki nilai jual yang lebih tinggi daripada red claw berwarna coklat.  Tujuan penelitian ini untuk mengetahui pengaruh penambahan wortel sebagai sumber beta karoten alami dengan beberapa metoda pengolahan pada pakan terhadap peningkatan warna biru lobster red claw. Penelitian menggunakan Rancangan Acak Lengkap dengan 4 perlakuan : A (kontrol, B (ekstrak, C (jus dan D (serutan wortel dengan menggunakan dosis 45 ppm beta karoten dan ulangan 5 kali.  Data dianalisis dengan uji Kruskal-Wallis dan dilanjutkan dengan uji Z.  Hasil penelitian menunjukkan bahwa penambahan wortel sebagai sumber beta karoten alami dengan beberapa metode

  12. Satellite Cells CD44 Positive Drive Muscle Regeneration in Osteoarthritis Patients

    Science.gov (United States)

    Scimeca, Manuel; Bonanno, Elena; Piccirilli, Eleonora; Baldi, Jacopo; Mauriello, Alessandro; Orlandi, Augusto; Tancredi, Virginia; Gasbarra, Elena; Tarantino, Umberto

    2015-01-01

    Age-related bone diseases, such as osteoarthritis and osteoporosis, are strongly associated with sarcopenia and muscle fiber atrophy. In this study, we analyzed muscle biopsies in order to demonstrate that, in osteoarthritis patients, both osteophytes formation and regenerative properties of muscle stem cells are related to the same factors. In particular, thanks to immunohistochemistry, transmission electron microscopy, and immunogold labeling we investigated the role of BMP-2 in muscle stem cells activity. In patients with osteoarthritis both immunohistochemistry and transmission electron microscopy allowed us to note a higher number of CD44 positive satellite muscle cells forming syncytium. Moreover, the perinuclear and cytoplasmic expression of BMP-2 assessed by in situ molecular characterization of satellite cells syncytia suggest a very strict correlation between BMP-2 expression and muscle regeneration capability. Summing up, the higher BMP-2 expression in osteoarthritic patients could explain the increased bone mineral density as well as decreased muscle atrophy in osteoarthrosic patients. In conclusion, our results suggest that the control of physiological BMP-2 balance between bone and muscle tissues may be considered as a potential pharmacological target in bone-muscle related pathology. PMID:26101529

  13. Satellite Cells CD44 Positive Drive Muscle Regeneration in Osteoarthritis Patients

    Directory of Open Access Journals (Sweden)

    Manuel Scimeca

    2015-01-01

    Full Text Available Age-related bone diseases, such as osteoarthritis and osteoporosis, are strongly associated with sarcopenia and muscle fiber atrophy. In this study, we analyzed muscle biopsies in order to demonstrate that, in osteoarthritis patients, both osteophytes formation and regenerative properties of muscle stem cells are related to the same factors. In particular, thanks to immunohistochemistry, transmission electron microscopy, and immunogold labeling we investigated the role of BMP-2 in muscle stem cells activity. In patients with osteoarthritis both immunohistochemistry and transmission electron microscopy allowed us to note a higher number of CD44 positive satellite muscle cells forming syncytium. Moreover, the perinuclear and cytoplasmic expression of BMP-2 assessed by in situ molecular characterization of satellite cells syncytia suggest a very strict correlation between BMP-2 expression and muscle regeneration capability. Summing up, the higher BMP-2 expression in osteoarthritic patients could explain the increased bone mineral density as well as decreased muscle atrophy in osteoarthrosic patients. In conclusion, our results suggest that the control of physiological BMP-2 balance between bone and muscle tissues may be considered as a potential pharmacological target in bone-muscle related pathology.

  14. Clawed forelimbs allow northern seals to eat like their ancient ancestors

    Science.gov (United States)

    Hocking, David P.; Marx, Felix G.; Sattler, Renae; Harris, Robert N.; Pollock, Tahlia I.; Sorrell, Karina J.; Fitzgerald, Erich M. G.; McCurry, Matthew R.; Evans, Alistair R.

    2018-04-01

    Streamlined flippers are often considered the defining feature of seals and sea lions, whose very name `pinniped' comes from the Latin pinna and pedis, meaning `fin-footed'. Yet not all pinniped limbs are alike. Whereas otariids (fur seals and sea lions) possess stiff streamlined forelimb flippers, phocine seals (northern true seals) have retained a webbed yet mobile paw bearing sharp claws. Here, we show that captive and wild phocines routinely use these claws to secure prey during processing, enabling seals to tear large fish by stretching them between their teeth and forelimbs. `Hold and tear' processing relies on the primitive forelimb anatomy displayed by phocines, which is also found in the early fossil pinniped Enaliarctos. Phocine forelimb anatomy and behaviour therefore provide a glimpse into how the earliest seals likely fed, and indicate what behaviours may have assisted pinnipeds along their journey from terrestrial to aquatic feeding.

  15. MRI appearance of muscle denervation

    Energy Technology Data Exchange (ETDEWEB)

    Kamath, S. [University Hospital of Wales, Department of Radiology, Cardiff (United Kingdom); Venkatanarasimha, N.; Walsh, M.A.; Hughes, P.M. [Derriford Hospital, Department of Radiology, Plymouth (United Kingdom)

    2008-05-15

    Muscle denervation results from a variety of causes including trauma, neoplasia, neuropathies, infections, autoimmune processes and vasculitis. Traditionally, the diagnosis of muscle denervation was based on clinical examination and electromyography. Magnetic resonance imaging (MRI) offers a distinct advantage over electromyography, not only in diagnosing muscle denervation, but also in determining its aetiology. MRI demonstrates characteristic signal intensity patterns depending on the stage of muscle denervation. The acute and subacutely denervated muscle shows a high signal intensity pattern on fluid sensitive sequences and normal signal intensity on T1-weighted MRI images. In chronic denervation, muscle atrophy and fatty infiltration demonstrate high signal changes on T1-weighted sequences in association with volume loss. The purpose of this review is to summarise the MRI appearance of denervated muscle, with special emphasis on the signal intensity patterns in acute and subacute muscle denervation. (orig.)

  16. Skeletal muscle metabolism in hypokinetic rats

    Science.gov (United States)

    Tischler, Marc E.

    1993-01-01

    This grant focused on the mechanisms of metabolic changes associated with unweighting atrophy and reduced growth of hind limb muscles of juvenile rats. Metabolic studies included a number of different areas. Amino acid metabolic studies placed particular emphasis on glutamine and branched-chain amino acid metabolism. These studies were an outgrowth of understanding stress effects and the role of glucocorticoids in these animals. Investigations on protein metabolism were largely concerned with selective loss of myofibrillar proteins and the role of muscle proteolysis. These investigations lead to finding important differences from denervation and atrophy and to define the roles of cytosolic versus lysosomal proteolysis in these atrophy models. A major outgrowth of these studies was demonstrating an ability to prevent atrophy of the unweighted muscle for at least 24 hours. A large amount of work concentrated on carbohydrate metabolism and its regulation by insulin and catecholamines. Measurements focused on glucose transport, glycogen metabolism, and glucose oxidation. The grant was used to develop an important new in situ approach for studying protein metabolism, glucose transport, and hormonal effects which involves intramuscular injection of various agents for up to 24 hours. Another important consequence of this project was the development and flight of Physiological-Anatomical Rodent Experiment-1 (PARE-1), which was launched aboard Space Shuttle Discovery in September 1991. Detailed descriptions of these studies can be found in the 30 peer-reviewed publications, 15 non-reviewed publications, 4 reviews and 33 abstracts (total 82 publications) which were or are scheduled to be published as a result of this project. A listing of these publications grouped by area (i.e. amino acid metabolism, protein metabolism, carbohydrate metabolism, and space flight studies) are included.

  17. Experiment K-6-09. Morphological and biochemical investigation of microgravity-induced nerve and muscle breakdown. Part 1: Investigation of nerve and muscle breakdown during spaceflight; Part 2: Biochemical analysis of EDL and PLT muscles

    Science.gov (United States)

    Riley, D. A.; Ellis, S.; Bain, J.; Sedlak, F.; Slocum, G.; Oganov, V.

    1990-01-01

    The present findings on rat hindlimb muscles suggest that skeletal muscle weakness induced by prolonged spaceflight can result from a combination of muscle fiber atrophy, muscle fiber segmental necrosis, degeneration of motor nerve terminals and destruction of microcirculatory vessels. Damage was confined to the red adductor longus (AL) and soleus muscles. The midbelly region of the AL muscle had more segmental necrosis and edema than the ends. Macrophages and neutrophils were the major mononucleated cells infiltrating and phagocytosing the cellular debris. Toluidine blue-positive mast cells were significantly decreased in Flight AL muscles compared to controls; this indicated that degranulation of mast cells contributed to tissue edema. Increased ubiquitination of disrupted myofibrils may have promoted myofilament degradation. Overall, mitochondria content and SDH activity were normal, except for a decrease in the subsarcolemmal region. The myofibrillar ATPase activity shifted toward the fast type in the Flight AL muscles. Some of the pathological changes may have occurred or been exacerbated during the 2 day postflight period of readaptation to terrestrial gravity. While simple atrophy should be reversible by exercise, restoration of pathological changes depends upon complex processes of regeneration by stem cells. Initial signs of muscle and nerve fiber regeneration were detected. Even though regeneration proceeds on Earth, the space environment may inhibit repair and cause progressive irreversible deterioration during long term missions. Muscles obtained from Flight rats sacrificed immediately (within a few hours) after landing are needed to distinguish inflight changes from postflight readaptation.

  18. The clinical application of absorbable intramedullary nail and claw plate on treating multiple rib fractures.

    Science.gov (United States)

    Chai, X; Lin, Q; Ruan, Z; Zheng, J; Zhou, J; Zhang, J

    2013-08-01

    The absorption intramedullary nail and claw plate indications and efficacy were investigated in the treatment of a life-threatening multiple rib fractures. A retrospective analysis of 248 surgically treated rib fracture patients was performed who admitted to our hospital from March 2007 to December 2012. Intramedullary nailing was performed in 28 cases, a claw-type bone plate was fixed in 141 cases, and a combination of both was fixed in 79 cases. All internal fixation patients were clinically cured except 1 patient died 14 days after a massive pulmonary embolism. The patients with flail chest and floating chest wall causing respiratory and circulatory disorders were promptly corrected. Routine follow-up was from 1 to 2 years, displaced fractures were in 2 cases, and there were 11 cases of internal fixation and extraction. Internal fixation is a simple and reliable method for the treatment of multiple rib fractures. Both internal fixation materials have their pros and cons but the claw bone plate is more robust. The actual selection of appropriate treatment options helps to improve the treatment efficacy.

  19. Time-Course of Muscle Mass Loss, Damage, and Proteolysis in Gastrocnemius following Unloading and Reloading: Implications in Chronic Diseases

    Science.gov (United States)

    Chacon-Cabrera, Alba; Lund-Palau, Helena; Gea, Joaquim; Barreiro, Esther

    2016-01-01

    Background Disuse muscle atrophy is a major comorbidity in patients with chronic diseases including cancer. We sought to explore the kinetics of molecular mechanisms shown to be involved in muscle mass loss throughout time in a mouse model of disuse muscle atrophy and recovery following immobilization. Methods Body and muscle weights, grip strength, muscle phenotype (fiber type composition and morphometry and muscle structural alterations), proteolysis, contractile proteins, systemic troponin I, and mitochondrial content were assessed in gastrocnemius of mice exposed to periods (1, 2, 3, 7, 15 and 30 days) of non-invasive hindlimb immobilization (plastic splint, I cohorts) and in those exposed to reloading for different time-points (1, 3, 7, 15, and 30 days, R cohorts) following a seven-day period of immobilization. Groups of control animals were also used. Results Compared to non-exposed controls, muscle weight, limb strength, slow- and fast-twitch cross-sectional areas, mtDNA/nDNA, and myosin content were decreased in mice of I cohorts, whereas tyrosine release, ubiquitin-proteasome activity, muscle injury and systemic troponin I levels were increased. Gastrocnemius reloading following splint removal improved muscle mass loss, strength, fiber atrophy, injury, myosin content, and mtDNA/nDNA, while reducing ubiquitin-proteasome activity and proteolysis. Conclusions A consistent program of molecular and cellular events leading to reduced gastrocnemius muscle mass and mitochondrial content and reduced strength, enhanced proteolysis, and injury, was seen in this non-invasive mouse model of disuse muscle atrophy. Unloading of the muscle following removal of the splint significantly improved the alterations seen during unloading, characterized by a specific kinetic profile of molecular events involved in muscle regeneration. These findings have implications in patients with chronic diseases including cancer in whom physical activity may be severely compromised. PMID

  20. Region-specific adaptations in determinants of rat skeletal muscle oxygenation to chronic hypoxia.

    NARCIS (Netherlands)

    Wust, R.C.; Jaspers, R.T.; Heyst, A.F.J. van; Hopman, M.T.E.; Hoofd, L.J.C.; Laarse, W.J. van der; Degens, H.

    2009-01-01

    Chronic exposure to hypoxia is associated with muscle atrophy (i.e., a reduction in muscle fiber cross-sectional area), reduced oxidative capacity, and capillary growth. It is controversial whether these changes are muscle and fiber type specific. We hypothesized that different regions of the same

  1. Mathematical models of human paralyzed muscle after long-term training

    OpenAIRE

    Frey Law, L.A.; Shields, R.K.

    2007-01-01

    Spinal cord injury (SCI) results in major musculoskeletal adaptations, including muscle atrophy, faster contractile properties, increased fatigability, and bone loss. The use of functional electrical stimulation (FES) provides a method to prevent paralyzed muscle adaptations in order to sustain force-generating capacity. Mathematical muscle models may be able to predict optimal activation strategies during FES, however muscle properties further adapt with long-term training. The purpose of th...

  2. Klinefelter′s syndrome associated with progressive muscular atrophy simulating Kennedy′s disease

    Directory of Open Access Journals (Sweden)

    Pedro Enrique Jiménez Caballero

    2012-01-01

    Full Text Available Kennedy′s disease, an X-linked spinal and bulbar muscular atrophy, is characterized by loss of lower motor neurons. Mild sensory deficits, gynecomastia and infertility may be observed. Klinefelter′s syndrome is a variation of sex chromosome disorder characterized by hypogonadism, gynecomastia and azoospermia, and the most frequent karyotype is XXY. A 55-year-old man who presented with slowly progressive and diffuse neurogenic muscle atrophy without bulbar or sensory symptoms. He also had Klinefelter′s syndrome. Genetic study of Kennedy′s disease was normal. Our patient differs from those with Kennedy′s disease in the absence of bulbar and sensory symptoms. It is suggested that the X chromosome plays an important role in the biology of motor neurons.

  3. Primary iris claw IOL retrofixation with intravitreal triamcinolone acetonide in cases of inadequate capsular support.

    Science.gov (United States)

    Kelkar, Aditya; Shah, Rachana; Vasavda, Viraj; Kelkar, Jai; Kelkar, Shreekant

    2018-02-01

    To assess the outcomes and analyze complication rates following primary iris claw IOL retrofixation with intravitreal triamcinolone acetonide. This is a retrospective interventional case series. Patients with poor capsular support-diagnosed preoperatively or owing to intraoperative complications-were treated with iris claw IOL retrofixation with intravitreal triamcinolone acetonide. The data were retrospectively analyzed. 104 eyes of 102 patients with poor capsular support who underwent the procedure between 2010 and 2013 were analyzed. The minimum follow-up period was 12 months (ranging from 12 to 36 months). Iris claw IOL was implanted in-traumatic subluxated cataracts-24 cases (23.07%), non-traumatic subluxated cataracts in 16 cases (15.38%), or as a complication of cataract surgery-intraoperative posterior capsular rent in 48 cases (46.15%) and intraoperative nucleus drop in 16 cases (15.38%). The final mean best-corrected logMAR visual acuity improved from 1.36 ± 0.64 preoperatively to 0.36 ± 0.32 at 1-year follow-up. Complications included pupil ovalization in 11 cases (10.57%), transient elevation in intraocular pressure in 7 eyes (6.73%), postoperative hypotony in 5 eyes (4.80%), cystoid macular edema in 2 eyes (1.92%), retinal detachment in 1 eye (0.96%), vitreous hemorrhage in 1 eye (0.96%), and hyphema in 1 eye (0.96%). Primary iris claw IOL retrofixation provided excellent alternative in patients with inadequate capsular support. The visual outcomes were good along with favorable rates of complications. The addition of triamcinolone acetonide helps in reducing the chances of cystoid macular edema.

  4. 3-D finite element analysis of claw-poled stepping motor

    International Nuclear Information System (INIS)

    Kawase, Yoshihiro; Yamaguchi, Tadashi; Mizuno; Koike, Yoshikazu

    2002-01-01

    Stepping motors are widely used for various electric instruments. It is necessary for the optimum design to analyze the magnetic field accurately. The 3-D finite element method with edge elements taking into account the rotation of the rotor has been applied to analyze the magnetic field of a claw-poled stepping motor. (Author)

  5. MR imaging of muscle diseases

    International Nuclear Information System (INIS)

    Kaiser, W.A.; Zeitler, E.; Schalke, B.C.G.

    1986-01-01

    Because of high soft-tissue contrast, MR imaging is especially suitable for the investigation of muscle diseases. Between March 1984 and March 1986, 76 patients with different types of muscle diseases were examined using a 1-T superconductive magnet (Siemens Magnetom). Studied were 14 patients with progressive muscular dystrophy (including carriers), 32 patients with myositis, four patients with myotonic dystrophy, six patients with spinal muscular atrophy, and 20 patients with other muscle diseases, including metabolic disorders. MR imaging showed typical signal patterns in affected muscle groups. These patterns can be used in the differential diagnosis, in biopsy planning, or in evaluation of response to therapy. The T1/T2 ratio especially seems to indicate very early stages of muscle disease

  6. Protein synthesis rates in atrophied gastrocnemius muscles after limb immobilization

    Science.gov (United States)

    Tucker, K. R.; Seider, M. J.; Booth, F. W.

    1981-01-01

    Noting that protein synthesis declines in the gastrocnemius 6 hr after immobilization, the study sought to detect an increase of protein synthesis when the limb was freed, and to examine the effects of exercise on the rate of increase. Rats were used as subjects, with their hind legs in plaster of Paris in plantar flexion to eliminate strain on the gastrocnemius. Periods of immobilization were varied and samples of blood from the muscle were taken to track protein synthesis rates for different groups in immobilization and exercise regimens (running and weightlifting). Synthesis rates declined 3.6% during time in the cast, then increased 6.3%/day after the casts were removed. Both running and weightlifting were found to increase the fractional rate of protein formation in the gastrocnemius muscle when compared with contralateral muscles that were not exercised and were used as controls, suggesting that the mechanism controlling protein synthesis in skeletal muscles is rapidly responsive to changes in muscular contractile activity.

  7. Negative Energy Balance Induced by Paradoxical Sleep Deprivation Causes Multicompartmental Changes in Adipose Tissue and Skeletal Muscle

    Directory of Open Access Journals (Sweden)

    Marcos Mônico-Neto

    2015-01-01

    Full Text Available Objective. Describe multicompartmental changes in the fat and various muscle fiber types, as well as the hormonal profile and metabolic rate induced by SD in rats. Methods. Twenty adult male Wistar rats were equally distributed into two groups: experimental group (EG and control group (CG. The EG was submitted to SD for 96 h. Blood levels of corticosterone (CORT, total testosterone (TESTO, insulin like growth factor-1 (IGF-1, and thyroid hormones (T3 and T4 were used to assess the catabolic environment. Muscle trophism was measured using a cross-sectional area of various muscles (glycolytic, mixed, and oxidative, and lipolysis was inferred by the weight of fat depots from various locations, such as subcutaneous, retroperitoneal, and epididymal. The metabolic rate was measured using oxygen consumption (V˙O2 measurement. Results. SD increased CORT levels and decreased TESTO, IGF-1, and T4. All fat depots were reduced in weight after SD. Glycolytic and mixed muscles showed atrophy, whereas atrophy was not observed in oxidative muscle. Conclusion. Our data suggest that glycolytic muscle fibers are more sensitive to atrophy than oxidative fibers during SD and that fat depots are reduced regardless of their location.

  8. The vertical ground reaction force and the pressure distribution on the claws of dairy cows while walking on a flat substrate

    NARCIS (Netherlands)

    Tol, van der P.P.J.; Metz, J.H.M.; Noordhuizen-Stassen, E.N.; Back, W.; Braam, C.R.; Weijs, W.A.

    2003-01-01

    The pressure distribution under the bovine claw while walking was measured to test the hypotheses that the vertical ground reaction force is unevenly distributed and makes some (regions of the) claws more prone to injuries due to overloading than others. Each limb of nine recently trimmed Holstein

  9. Overexpression of IGF-1 attenuates skeletal muscle damage and accelerates muscle regeneration and functional recovery after disuse

    Science.gov (United States)

    Ye, Fan; Mathur, Sunita; Liu, Min; Borst, Stephen E.; Walter, Glenn A.; Sweeney, H. Lee; Vandenborne, Krista

    2014-01-01

    Skeletal muscle is a highly dynamic tissue that responds to endogenous and external stimuli, including alterations in mechanical loading and growth factors. In particular, the antigravity soleus muscle experiences significant muscle atrophy during disuse and extensive muscle damage upon reloading. Since insulin-like growth factor-1 (IGF-1) has been implicated as a central regulator of muscle repair and modulation of muscle size, we examined the effect of viral mediated overexpression of IGF-1 on the soleus muscle following hindlimb cast immobilization and upon reloading. Recombinant IGF-1 cDNA virus was injected into one of the posterior hindlimbs of the mice, while the contralateral limb was injected with saline (control). At 20 weeks of age, both hindlimbs were immobilized for two weeks to induce muscle atrophy in the soleus and ankle plantar flexor muscle group. Subsequently, the mice were allowed to reambulate and muscle damage and recovery was monitored over a period of 2 to 21 days. The primary finding of this study was that IGF-1 overexpression attenuated reloading-induced muscle damage in the soleus muscle, and accelerated muscle regeneration and force recovery. Muscle T2 assessed by MRI, a nonspecific marker of muscle damage, was significantly lower in IGF-1 injected, compared to contralateral soleus muscles at 2 and 5 days reambulation (P<0.05). The reduced prevalence of muscle damage in IGF-1 injected soleus muscles was confirmed on histology, with a lower fraction area of abnormal muscle tissue in IGF-I injected muscles at 2 days reambulation (33.2±3.3%vs 54.1±3.6%, P<0.05). Evidence of the effect of IGF-1 on muscle regeneration included timely increases in the number of central nuclei (21% at 5 days reambulation), paired-box transcription factor 7 (36% at 5 days), embryonic myosin (37% at 10 days), and elevated MyoD mRNA (7-fold at 2 days) in IGF-1 injected limbs (P<0.05). These findings demonstrate a potential role of IGF-1 in protecting unloaded

  10. Brain atrophy during aging

    International Nuclear Information System (INIS)

    Matsuzawa, Taiju; Takeda, Shumpei; Hatazawa, Jun

    1985-01-01

    Age-related brain atrophy was investigated in thousands of persons with no neurologic disturbances using X-CT and NMR-CT and following results were obtained. Brain atrophy was minimal in 34 -- 35 years old in both sexes, increased exponentially to the increasing age after 34 -- 35 years, and probably resulted in dementia, such as vascular or multiinfarct dementia. Brain atrophy was significantly greater in men than in women at all ages. Brain volumes were maximal in 34 -- 35 years old in both sexes with minimal individual differences which increased proportionally to the increasing age. Remarkable individual differences in the extents of brain atrophy (20 -- 30 %) existed among aged subjects. Some aged subjects had little or no atrophy of their brains, as seen in young subjects, and others had markedly shrunken brains associated with senility. From these results there must be pathological factors promoting brain atrophy with a great individual difference. We have studied the relation of intelligence to brain volume, and have ascertained that progression of brain atrophy was closely related to loss of mental activities independently of their ages. Our longitudinal study has revealed that the most important factors promoting brain atrophy during aging was decrease in the cerebral blood flow. MNR-CT can easily detected small infarction (lacunae) and edematous lesions resulting from ischemia and hypertensive encephalopathy, while X-CT can not. Therefore NMR-CT is very useful for detection of subtle changes in the brain. (J.P.N.)

  11. Molecular Mechanisms of Neurodegeneration in Spinal Muscular Atrophy

    Directory of Open Access Journals (Sweden)

    Saif Ahmad

    2016-01-01

    Full Text Available Spinal muscular atrophy (SMA is an autosomal recessive motor neuron disease with a high incidence and is the most common genetic cause of infant mortality. SMA is primarily characterized by degeneration of the spinal motor neurons that leads to skeletal muscle atrophy followed by symmetric limb paralysis, respiratory failure, and death. In humans, mutation of the Survival Motor Neuron 1 (SMN1 gene shifts the load of expression of SMN protein to the SMN2 gene that produces low levels of full-length SMN protein because of alternative splicing, which are sufficient for embryonic development and survival but result in SMA. The molecular mechanisms of the (a regulation of SMN gene expression and (b degeneration of motor neurons caused by low levels of SMN are unclear. However, some progress has been made in recent years that have provided new insights into understanding of the cellular and molecular basis of SMA pathogenesis. In this review, we have briefly summarized recent advances toward understanding of the molecular mechanisms of regulation of SMN levels and signaling mechanisms that mediate neurodegeneration in SMA.

  12. Computed tomographic myelography characteristics of spinal cord atrophy in juvenile muscular atrophy of the upper extremity

    International Nuclear Information System (INIS)

    Hirabuki, Norio; Mitomo, Masanori; Miura, Takashi; Hashimoto, Tsutomu; Kawai, Ryuji; Kozuka, Takahiro

    1991-01-01

    Although atrophy of the lower cervical and upper thoracic cord in juvenile muscular atrophy of distal upper extremity has been reported, the atrophic patterns of the cord, especially in the transverse section, have not been studied extensively. The aim of this study is to clarify the atrophic patterns of the cord by CT myelography (CTM) and to discuss the pathogenesis of cord atrophy. Sixteen patients with juvenile muscular atrophy of distal upper extremity were examined by CTM. Atrophy of the lower cervical and upper thoracic cord, consistent with the segmental weakness, was seen in all patients. Flattening of the ventral convexity was a characteristic atrophic pattern of the cord. Bilateral cord atrophy was commonly observed; 8/12 patients with unilateral clinical form and all 4 patients with bilateral form showed bilateral cord atrophy with dominance on the clinical side. There was no correlation between the degree of cord atrophy and duration of symptoms. Flattening of the ventral convexity, associated with purely motor disturbances, reflects selective atrophy of the anterior horns in the cord, which is attributable to chronic ischemia. Cord atrophy proved to precede clinical manifestations. The characteristic atrophy of the cord provides useful information to confirm the diagnosis without long-term observation. (author). 21 refs.; 3 figs.; 2 tabs

  13. Growth factor involvement in tension-induced skeletal muscle growth

    Science.gov (United States)

    Vandenburgh, Herman H.

    1993-01-01

    Long-term manned space travel will require a better understanding of skeletal muscle atrophy which results from microgravity. Astronaut strength and dexterity must be maintained for normal mission operations and for emergency situations. Although exercise in space slows the rate of muscle loss, it does not prevent it. A biochemical understanding of how gravity/tension/exercise help to maintain muscle size by altering protein synthesis and/or degradation rate should ultimately allow pharmacological intervention to prevent muscle atrophy in microgravity. The overall objective is to examine some of the basic biochemical processes involved in tension-induced muscle growth. With an experimental in vitro system, the role of exogenous and endogenous muscle growth factors in mechanically stimulated muscle growth are examined. Differentiated avian skeletal myofibers can be 'exercised' in tissue culture using a newly developed dynamic mechanical cell stimulator device which simulates different muscle activity patterns. Patterns of mechanical activity which significantly affect muscle growth and metabolic characteristics were found. Both exogenous and endogenous growth factors are essential for tension-induced muscle growth. Exogenous growth factors found in serum, such as insulin, insulin-like growth factors, and steroids, are important regulators of muscle protein turnover rates and mechanically-induced muscle growth. Endogenous growth factors are synthesized and released into the culture medium when muscle cells are mechanically stimulated. At least one family of mechanically induced endogenous factors, the prostaglandins, help to regulate the rates of protein turnover in muscle cells. Endogenously synthesized IGF-1 is another. The interaction of muscle mechanical activity and these growth factors in the regulation of muscle protein turnover rates with our in vitro model system is studied.

  14. Expression of muscle anabolic and metabolic factors in mechanically loaded MLO-Y4 osteocytes

    NARCIS (Netherlands)

    Juffer, P.; Jaspers, R.T.; Lips, P.; Bakker, A.D.; Klein-Nulend, J.

    2012-01-01

    Lack of physical activity results in muscle atrophy and bone loss, which can be counteracted by mechanical loading. Similar molecular signaling pathways are involved in the adaptation of muscle and bone mass to mechanical loading. Whether anabolic and metabolic factors regulating muscle mass, i.e.,

  15. Electrophysiological, histochemical, and hormonal adaptation of rat muscle after prolonged hindlimb suspension

    Science.gov (United States)

    Kourtidou-Papadeli, Chrysoula; Kyparos, Antonios; Albani, Maria; Frossinis, Athanasios; Papadelis, Christos L.; Bamidis, Panagiotis; Vivas, Ana; Guiba-Tziampiri, Olympia

    2004-05-01

    The perspective of long-duration flights for future exploration, imply more research in the field of human adaptation. Previous studies in rat muscles hindlimb suspension (HLS), indicated muscle atrophy and a change of fibre composition from slow-to-fast twitch types. However, the contractile responses to long-term unloading is still unclear. Fifteen adult Wistar rats were studied in 45 and 70 days of muscle unweighting and soleus (SOL) muscle as well as extensor digitorum longus (EDL) were prepared for electrophysiological recordings (single, twitch, tetanic contraction and fatigue) and histochemical stainings. The loss of muscle mass observed was greater in the soleus muscle. The analysis of electrophysiological properties of both EDL and SOL showed significant main effects of group, of number of unweighting days and fatigue properties. Single contraction for soleus muscle remained unchanged but there was statistically significant difference for tetanic contraction and fatigue. Fatigue index showed a decrease for the control rats, but increase for the HLS rats. According to the histochemical findings there was a shift from oxidative to glycolytic metabolism during HLS. The data suggested that muscles atrophied, but they presented an adaptation pattern, while their endurance in fatigue was decreased.

  16. Genetic evaluation of claw health traits accounting for potential preselection of cows to be trimmed.

    Science.gov (United States)

    Croué, Iola; Fikse, Freddy; Johansson, Kjell; Carlén, Emma; Thomas, Gilles; Leclerc, Hélène; Ducrocq, Vincent

    2017-10-01

    Claw lesions are one of the most important health issues in dairy cattle. Although the frequency of claw lesions depends greatly on herd management, the frequency can be lowered through genetic selection. A genetic evaluation could be developed based on trimming records collected by claw trimmers; however, not all cows present in a herd are usually selected by the breeder to be trimmed. The objectives of this study were to investigate the importance of the preselection of cows for trimming, to account for this preselection, and to estimate genetic parameters of claw health traits. The final data set contained 25,511 trimming records of French Holstein cows. Analyzed claw lesion traits were digital dermatitis, heel horn erosion, interdigital hyperplasia, sole hemorrhage circumscribed, sole hemorrhage diffused, sole ulcer, and white line fissure. All traits were analyzed as binary traits in a multitrait linear animal model. Three scenarios were considered: including only trimmed cows in a 7-trait model (scenario 1); or trimmed cows and contemporary cows not trimmed but present at the time of a visit (considering that nontrimmed cows were healthy) in a 7-trait model (scenario 2); or trimmed cows and contemporary cows not trimmed but present at the time of a visit (considering lesion records for trimmed cows only), in an 8-trait model, including a 0/1 trimming status trait (scenario 3). For scenario 3, heritability estimates ranged from 0.02 to 0.09 on the observed scale. Genetic correlations clearly revealed 2 groups of traits (digital dermatitis, heel horn erosion, and interdigital hyperplasia on the one hand, and sole hemorrhage circumscribed, sole hemorrhage diffused, sole ulcer, and white line fissure on the other hand). Heritabilities on the underlying scale did not vary much depending on the scenario: the effect of the preselection of cows for trimming on the estimation of heritabilities appeared to be negligible. However, including untrimmed cows as healthy

  17. Molecular responses to moderate endurance exercise in skeletal muscle

    Science.gov (United States)

    This study examined alterations in skeletal-muscle growth and atrophy-related molecular events after a single bout of moderate-intensity endurance exercise. Muscle biopsies were obtained from 10 men (23 +/- 1 yr, body mass 80 +/- 2 kg, and VO(2peak) 45 +/- 1 ml x kg'¹ x min'¹) immediately (0 hr) and...

  18. Reversing Age Related Changes of the Laryngeal Muscles by Chronic Electrostimulation of the Recurrent Laryngeal Nerve.

    Directory of Open Access Journals (Sweden)

    Michael Karbiener

    Full Text Available Age related atrophy of the laryngeal muscles -mainly the thyroarytenoid muscle (TAM- leads to a glottal gap and consequently to a hoarse and dysphonic voice that significantly affects quality of life. The aim of our study was to reverse this atrophy by inducing muscular hypertrophy by unilateral functional electrical stimulation (FES of the recurrent laryngeal nerve (RLN in a large animal model using aged sheep (n = 5. Suitable stimulation parameters were determined by fatiguing experiments of the thyroarytenoid muscle in an acute trial. For the chronic trial an electrode was placed around the right RLN and stimulation was delivered once daily for 29 days. We chose a very conservative stimulation pattern, total stimulation time was two minutes per day, or 0.14% of total time. Overall, the mean muscle fiber diameter of the stimulated right TAM was significantly larger than the non-stimulated left TAM (30μm±1.1μm vs. 28μm±1.1 μm, p<0.001. There was no significant shift in fiber type distribution as judged by immunohistochemistry. The changes of fiber diameter could not be observed in the posterior cricoarytenoid muscle (PCAM. FES is a possible new treatment option for reversing the effects of age related laryngeal muscle atrophy.

  19. Valproic acid attenuates skeletal muscle wasting by inhibiting C/EBPβ-regulated atrogin1 expression in cancer cachexia.

    Science.gov (United States)

    Sun, Rulin; Zhang, Santao; Hu, Wenjun; Lu, Xing; Lou, Ning; Yang, Zhende; Chen, Shaoyong; Zhang, Xiaoping; Yang, Hongmei

    2016-07-01

    Muscle wasting is the hallmark of cancer cachexia and is associated with poor quality of life and increased mortality. Valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, has important biological effects in the treatment of muscular dystrophy. To verify whether VPA could ameliorate muscle wasting induced by cancer cachexia, we explored the role of VPA in two cancer cachectic mouse models [induced by colon-26 (C26) adenocarcinoma or Lewis lung carcinoma (LLC)] and atrophied C2C12 myotubes [induced by C26 cell conditioned medium (CCM) or LLC cell conditioned medium (LCM)]. Our data demonstrated that treatment with VPA increased the mass and cross-sectional area of skeletal muscles in tumor-bearing mice. Furthermore, treatment with VPA also increased the diameter of myotubes cultured in conditioned medium. The skeletal muscles in cachectic mice or atrophied myotubes treated with VPA exhibited reduced levels of CCAAT/enhancer binding protein beta (C/EBPβ), resulting in atrogin1 downregulation and the eventual alleviation of muscle wasting and myotube atrophy. Moreover, atrogin1 promoter activity in myotubes was stimulated by CCM via activating the C/EBPβ-responsive cis-element and subsequently inhibited by VPA. In contrast to the effect of VPA on the levels of C/EBPβ, the levels of inactivating forkhead box O3 (FoxO3a) were unaffected. In summary, VPA attenuated muscle wasting and myotube atrophy and reduced C/EBPβ binding to atrogin1 promoter locus in the myotubes. Our discoveries indicate that HDAC inhibition by VPA might be a promising new approach for the preservation of skeletal muscle in cancer cachexia. Copyright © 2016 the American Physiological Society.

  20. Muscles in a mouse model of spinal muscular atrophy show profound defects in neuromuscular development even in the absence of failure in neuromuscular transmission or loss of motor neurons.

    Science.gov (United States)

    Lee, Young Il; Mikesh, Michelle; Smith, Ian; Rimer, Mendell; Thompson, Wesley

    2011-08-15

    A mouse model of the devastating human disease "spinal muscular atrophy" (SMA) was used to investigate the severe muscle weakness and spasticity that precede the death of these animals near the end of the 2nd postnatal week. Counts of motor units to the soleus muscle as well as of axons in the soleus muscle nerve showed no loss of motor neurons. Similarly, neither immunostaining of neuromuscular junctions nor the measurement of the tension generated by nerve stimulation gave evidence of any significant impairment in neuromuscular transmission, even when animals were maintained up to 5days longer via a supplementary diet. However, the muscles were clearly weaker, generating less than half their normal tension. Weakness in 3 muscles examined in the study appears due to a severe but uniform reduction in muscle fiber size. The size reduction results from a failure of muscle fibers to grow during early postnatal development and, in soleus, to a reduction in number of fibers generated. Neuromuscular development is severely delayed in these mutant animals: expression of myosin heavy chain isoforms, the elimination of polyneuronal innervation, the maturation in the shape of the AChR plaque, the arrival of SCs at the junctions and their coverage of the nerve terminal, the development of junctional folds. Thus, if SMA in this particular mouse is a disease of motor neurons, it can act in a manner that does not result in their death or disconnection from their targets but nonetheless alters many aspects of neuromuscular development. Copyright © 2011 Elsevier Inc. All rights reserved.

  1. Columbia SMA Project: A Randomized, Control Trial of the Effects of Exercise on Motor Function and Strength in Patients with Spinal Muscular Atrophy (SMA)

    Science.gov (United States)

    2012-06-01

    management of the disease. Manual muscle testing (MMT) is performed as part of a routine neurological exam. Manual muscle testing (MMT) was found to be...dynamometry in spinal muscular atrophy. Muscle Nerve. 2002;26(1):64-70. Mostert & Kesselring. Effects of a short-term exercise training program on aerobic...dictated by the diseased motor neuron. The surviving muscles have more viable hypertrophied type 1 motor units possibly resulting in a lower MPF. Our

  2. The TWEAK–Fn14 dyad is involved in age-associated pathological changes in skeletal muscle

    International Nuclear Information System (INIS)

    Tajrishi, Marjan M.; Sato, Shuichi; Shin, Jonghyun; Zheng, Timothy S.; Burkly, Linda C.; Kumar, Ashok

    2014-01-01

    Highlights: • The levels of TWEAK receptor Fn14 are increased in skeletal muscle during aging. • Deletion of Fn14 attenuates age-associated skeletal muscle fiber atrophy. • Deletion of Fn14 inhibits proteolysis in skeletal muscle during aging. • TWEAK–Fn14 signaling activates transcription factor NF-κB in aging skeletal muscle. • TWEAK–Fn14 dyad is involved in age-associated fibrosis in skeletal muscle. - Abstract: Progressive loss of skeletal muscle mass and strength (sarcopenia) is a major clinical problem in the elderly. Recently, proinflammatory cytokine TWEAK and its receptor Fn14 were identified as key mediators of muscle wasting in various catabolic states. However, the role of the TWEAK–Fn14 pathway in pathological changes in skeletal muscle during aging remains unknown. In this study, we demonstrate that the levels of Fn14 are increased in skeletal muscle of 18-month old (aged) mice compared with adult mice. Genetic ablation of Fn14 significantly increased the levels of specific muscle proteins and blunted the age-associated fiber atrophy in mice. While gene expression of two prominent muscle-specific E3 ubiquitin ligases MAFBx and MuRF1 remained comparable, levels of ubiquitinated proteins and the expression of autophagy-related molecule Atg12 were significantly reduced in Fn14-knockout (KO) mice compared with wild-type mice during aging. Ablation of Fn14 significantly diminished the DNA-binding activity of transcription factor nuclear factor-kappa B (NF-κB), gene expression of various inflammatory molecules, and interstitial fibrosis in skeletal muscle of aged mice. Collectively, our study suggests that the TWEAK–Fn14 signaling axis contributes to age-associated muscle atrophy and fibrosis potentially through its local activation of proteolytic systems and inflammatory pathways

  3. The TWEAK–Fn14 dyad is involved in age-associated pathological changes in skeletal muscle

    Energy Technology Data Exchange (ETDEWEB)

    Tajrishi, Marjan M.; Sato, Shuichi; Shin, Jonghyun [Department of Anatomical Sciences and Neurobiology, University of Louisville School of Medicine, Louisville, KY 40202 (United States); Zheng, Timothy S.; Burkly, Linda C. [Department of Immunology, Biogen Idec, 14 Cambridge Center, Cambridge, MA 02142 (United States); Kumar, Ashok [Department of Anatomical Sciences and Neurobiology, University of Louisville School of Medicine, Louisville, KY 40202 (United States)

    2014-04-18

    Highlights: • The levels of TWEAK receptor Fn14 are increased in skeletal muscle during aging. • Deletion of Fn14 attenuates age-associated skeletal muscle fiber atrophy. • Deletion of Fn14 inhibits proteolysis in skeletal muscle during aging. • TWEAK–Fn14 signaling activates transcription factor NF-κB in aging skeletal muscle. • TWEAK–Fn14 dyad is involved in age-associated fibrosis in skeletal muscle. - Abstract: Progressive loss of skeletal muscle mass and strength (sarcopenia) is a major clinical problem in the elderly. Recently, proinflammatory cytokine TWEAK and its receptor Fn14 were identified as key mediators of muscle wasting in various catabolic states. However, the role of the TWEAK–Fn14 pathway in pathological changes in skeletal muscle during aging remains unknown. In this study, we demonstrate that the levels of Fn14 are increased in skeletal muscle of 18-month old (aged) mice compared with adult mice. Genetic ablation of Fn14 significantly increased the levels of specific muscle proteins and blunted the age-associated fiber atrophy in mice. While gene expression of two prominent muscle-specific E3 ubiquitin ligases MAFBx and MuRF1 remained comparable, levels of ubiquitinated proteins and the expression of autophagy-related molecule Atg12 were significantly reduced in Fn14-knockout (KO) mice compared with wild-type mice during aging. Ablation of Fn14 significantly diminished the DNA-binding activity of transcription factor nuclear factor-kappa B (NF-κB), gene expression of various inflammatory molecules, and interstitial fibrosis in skeletal muscle of aged mice. Collectively, our study suggests that the TWEAK–Fn14 signaling axis contributes to age-associated muscle atrophy and fibrosis potentially through its local activation of proteolytic systems and inflammatory pathways.

  4. Patterns of Age-Associated Degeneration Differ in Shoulder Muscles

    Science.gov (United States)

    Raz, Yotam; Henseler, Jan F.; Kolk, Arjen; Riaz, Muhammad; van der Zwaal, Peer; Nagels, Jochem; Nelissen, Rob G. H. H.; Raz, Vered

    2015-01-01

    Shoulder complaints are common in the elderly and hamper daily functioning. These complaints are often caused by tears in the muscle-tendon units of the rotator cuff (RC). The four RC muscles stabilize the shoulder joint. While some RC muscles are frequently torn in shoulder complaints others remain intact. The pathological changes in RC muscles are poorly understood. We investigated changes in RC muscle pathology combining radiological and histological procedures. We measured cross sectional area (CSA) and fatty infiltration from Magnetic Resonance Imaging with Arthrography (MRA) in subjects without (N = 294) and with (N = 109) RC-tears. Normalized muscle CSA of the four RC muscles and the deltoid shoulder muscle were compared and age-associated patterns of muscle atrophy and fatty infiltration were constructed. We identified two distinct age-associated patterns: in the supraspinatus and subscapularis RC muscles CSAs continuously declined throughout adulthood, whereas in the infraspinatus and deltoid reduced CSA was prominent from midlife onwards. In the teres minor, CSA was unchanged with age. Most importantly, age-associated patterns were highly similar between subjects without RC tear and those with RC-tears. This suggests that extensive RC muscle atrophy during aging could contribute to RC pathology. We compared muscle pathology between torn infraspinatus and non-torn teres minor and the deltoid in two patients with a massive RC-tear. In the torn infraspinatus we found pronounced fatty droplets, an increase in extracellular collagen-1, a loss of myosin heavy chain-1 expression in myofibers and an increase in Pax7-positive cells. However, the adjacent intact teres minor and deltoid exhibited healthy muscle features. This suggests that satellite cells and the extracellular matrix may contribute to extensive muscle fibrosis in torn RC. We suggest that torn RC muscles display hallmarks of muscle aging whereas the teres minor could represent an aging

  5. Patterns of age-associated degeneration differ in shoulder muscles

    Directory of Open Access Journals (Sweden)

    Yotam eRaz

    2015-12-01

    Full Text Available Shoulder complaints are common in the elderly and hamper daily functioning. These complaints are often caused by tears in the muscle-tendon units of the rotator cuff (RC. The four RC muscles stabilize the shoulder joint. While some RC muscles are frequently torn in shoulder complaints others remain intact. The pathological changes in RC muscles are poorly understood. We investigated changes in RC muscle pathology combining radiological and histological procedures. We measured cross sectional area (CSA and fatty infiltration from Magnetic Resonance Imaging with Arthrography in subjects without (N=294 and with (N=109 RC-tears. Normalized muscle CSA of the four RC muscles and the deltoid shoulder muscle were compared and age-associated patterns of muscle atrophy and fatty infiltration were constructed. We identified two distinct age-associated patterns: in the supraspinatus and subscapularis RC muscles CSAs continuously declined throughout adulthood, whereas in the infraspinatus and deltoid reduced CSA was prominent from midlife onwards. In the teres minor, CSA was unchanged with age. Most importantly, age-associated patterns were highly similar between subjects without RC tear and those with RC-tears. This suggests that extensive RC muscle atrophy during aging could contribute to RC pathology. We compared muscle pathology between torn infraspinatus and non-torn teres minor and the deltoid in two patients with a massive RC-tear. In the torn infraspinatus we found pronounced fatty droplets, an increase in extracellular collagen-1, a loss of myosin heavy chain-1 expression in myofibers and an increase in Pax7-positive cells. However, the adjacent intact teres minor and deltoid exhibited healthy muscle features. This suggests that satellite cells and the extracellular matrix may contribute to extensive muscle fibrosis in torn RC. We suggest that torn RC muscles display hallmarks of muscle aging whereas the teres minor could represent an aging

  6. Rotator cuff muscles lose responsiveness to anabolic steroids after tendon tear and musculotendinous retraction: an experimental study in sheep.

    Science.gov (United States)

    Gerber, Christian; Meyer, Dominik C; Von Rechenberg, Brigitte; Hoppeler, Hans; Frigg, Robert; Farshad, Mazda

    2012-11-01

    Long-standing rotator cuff tendon tearing is associated with retraction, loss of work capacity, irreversible fatty infiltration, and atrophy of the rotator cuff muscles. Although continuous musculotendinous relengthening can experimentally restore muscular architecture, restoration of atrophy and fatty infiltration is hitherto impossible. Continuous relengthening with pharmacological stimulation of muscle growth using an anabolic steroid or insulin-like growth factor (IGF) can reverse atrophy and fatty infiltration as well as improve the work capacity of chronically retracted rotator cuff muscles in sheep. Controlled laboratory study. Sixteen weeks after tenotomy of the infraspinatus (ISP) tendon, atrophy and fatty infiltration had developed in the retracted ISP muscle. The musculotendinous unit was continuously relengthened in 14 sheep during 6 weeks: Four sheep were treated without pharmacological stimulation, 4 with intramuscular administration of an anabolic steroid, and 6 with IGF before final repair and rehabilitation (12 weeks). Changes were documented by intraoperative measurements of muscle work capacity, histology, and computed tomography/magnetic resonance imaging. Musculotendinous relengthening by continuous traction resulted in gains of length ranging from 0.7 cm in the IGF group to 1.3 cm in the control group. Fatty infiltration progressed in all groups, and the muscle's cross-sectional area ranged from 71% to 74% of the contralateral side at sacrifice and did not show any differences between groups in weight, volume, histological composition, or work capability of the muscle. The contralateral muscles in the anabolic steroid group, however, showed significantly higher (mean ± standard deviation) muscle work capacity of 10 ± 0.9 N·m than the contralateral muscles of the control group (6.8 ± 2.4 N·m) (P muscle fiber area as well as by an unusual gain in the animals' weight after injection of the anabolic steroid. Subcutaneous continuous

  7. Skeletal Muscle Magnetic Resonance Imaging of the Lower Limbs in Late-onset Lipid Storage Myopathy with Electron Transfer Flavoprotein Dehydrogenase Gene Mutations

    Institute of Scientific and Technical Information of China (English)

    Xin-Yi Liu; Ming Jin; Zhi-Qiang Wang; Dan-Ni Wang; Jun-Jie He; Min-Ting Lin; Hong-Xia Fu

    2016-01-01

    Background:Lipid storage myopathy (LSM) is a genetically heterogeneous group with variable clinical phenotypes.Late-onset multiple acyl-coenzyme A dehydrogenation deficiency (MADD) is a rather common form of LSM in China.Diagnosis and clinical management of it remain challenging,especially without robust muscle biopsy result and genetic detection.As the noninvasion and convenience,muscle magnetic resonance imaging (MRI) is a helpful assistant,diagnostic tool for neuromuscular disorders.However,the disease-specific MRI patterns of muscle involved and its diagnostic value in late-onset MADD have not been systematic analyzed.Methods:We assessed the MRI pattern and fat infiltration degree of the lower limb muscles in 28 late-onset MADD patients,combined with detailed clinical features and gene spectrum.Fat infiltration degree of the thigh muscle was scored while that ofgluteus was described as obvious or not.Associated muscular atrophy was defined as obvious muscle bulk reduction.Results:The mean scores were significantly different among the anterior,medial,and posterior thigh muscle groups.The mean of fat infiltration scores on posterior thigh muscle group was significantly higher than either anterior or medial thigh muscle group (P < 0.001).Moreover,the mean score on medial thigh muscle group was significantly higher than that of anterior thigh muscle group (P < 0.01).About half of the patients displayed fat infiltration and atrophy in gluteus muscles.Of 28 patients,12 exhibited atrophy in medial and/or posterior thigh muscle groups,especially in posterior thigh muscle group.Muscle edema pattern was not found in all the patients.Conclusions:Late-onset MADD patients show a typical muscular imaging pattern of fat infiltration and atrophy on anterior,posterior,and medial thigh muscle groups,with major involvement of posterior thigh muscle group and gluteus muscles and a sparing involvement of anterior thigh compartment.Our findings also suggest that muscle MRI of

  8. The muscle CT of thigh in chronic Werdnig-Hoffmann disease

    International Nuclear Information System (INIS)

    Horikawa, Hirosei; Konagaya, Masaaki; Takayanagi, Tetsuya; Otsuji, Hideaki

    1986-01-01

    In this paper, the muscle CT of thigh in chronic Werdnig-Hoffmann disease (chronic WH) was evaluated. The subjects were five cases of chronic WH (3 males and 2 females, ages ranging from 6 to 22 years) and four control males. All cases showed symmetrical muscular weakness. The proximal muscle were more affected than the distal in the upper limbs. But the muscle strength of hip adduction was relatively spared as compared with other strength of lower limbs. The CT scan was carried out at the upper quarter level between lesser trochanter and medial condyle of the femur. The muscle CT of cases aged 6 and 7 years showed the severely decreased cross-sectional area of muscle without significant decrease in density. The atrophic muscles were surrounded by a large amount of low density area. The hamstring muscles and the adductor muscles, especially adductor longus muscle (ALM), were less affected than the quadriceps femoris muscles. Spotty and moth-eaten low density areas were observed dominantly in the severely affected muscles. In the advanced cases, only ALM could be identified on the CT image. The other muscles were unable to be identified because of severe atrophy with extremely low density. These CT findings suggest the process of muscular wastings of chronic WH as follows; at first muscle fibers are atrophied due to denervation and sooner or later replaced with fat tissue. Moreover, the preservation of ALM suggests that loss of anterior horn cells does not always go on homogeneously. (author)

  9. Adaptation of Mouse Skeletal Muscle to Long-Term Microgravity in the MDS Mission

    Science.gov (United States)

    Camerino, Giulia M.; Bianchini, Elisa; Ciciliot, Stefano; Danieli-Betto, Daniela; Dobrowolny, Gabriella; Furlan, Sandra; Germinario, Elena; Goto, Katsumasa; Gutsmann, Martina; Kawano, Fuminori; Nakai, Naoya; Ohira, Takashi; Ohno, Yoshitaka; Picard, Anne; Salanova, Michele; Schiffl, Gudrun; Blottner, Dieter; Musarò, Antonio; Ohira, Yoshinobu; Betto, Romeo; Conte, Diana; Schiaffino, Stefano

    2012-01-01

    The effect of microgravity on skeletal muscles has so far been examined in rat and mice only after short-term (5–20 day) spaceflights. The mice drawer system (MDS) program, sponsored by Italian Space Agency, for the first time aimed to investigate the consequences of long-term (91 days) exposure to microgravity in mice within the International Space Station. Muscle atrophy was present indistinctly in all fiber types of the slow-twitch soleus muscle, but was only slightly greater than that observed after 20 days of spaceflight. Myosin heavy chain analysis indicated a concomitant slow-to-fast transition of soleus. In addition, spaceflight induced translocation of sarcolemmal nitric oxide synthase-1 (NOS1) into the cytosol in soleus but not in the fast-twitch extensor digitorum longus (EDL) muscle. Most of the sarcolemmal ion channel subunits were up-regulated, more in soleus than EDL, whereas Ca2+-activated K+ channels were down-regulated, consistent with the phenotype transition. Gene expression of the atrophy-related ubiquitin-ligases was up-regulated in both spaceflown soleus and EDL muscles, whereas autophagy genes were in the control range. Muscle-specific IGF-1 and interleukin-6 were down-regulated in soleus but up-regulated in EDL. Also, various stress-related genes were up-regulated in spaceflown EDL, not in soleus. Altogether, these results suggest that EDL muscle may resist to microgravity-induced atrophy by activating compensatory and protective pathways. Our study shows the extended sensitivity of antigravity soleus muscle after prolonged exposition to microgravity, suggests possible mechanisms accounting for the resistance of EDL, and individuates some molecular targets for the development of countermeasures. PMID:22470446

  10. Adaptation of mouse skeletal muscle to long-term microgravity in the MDS mission.

    Directory of Open Access Journals (Sweden)

    Dorianna Sandonà

    Full Text Available The effect of microgravity on skeletal muscles has so far been examined in rat and mice only after short-term (5-20 day spaceflights. The mice drawer system (MDS program, sponsored by Italian Space Agency, for the first time aimed to investigate the consequences of long-term (91 days exposure to microgravity in mice within the International Space Station. Muscle atrophy was present indistinctly in all fiber types of the slow-twitch soleus muscle, but was only slightly greater than that observed after 20 days of spaceflight. Myosin heavy chain analysis indicated a concomitant slow-to-fast transition of soleus. In addition, spaceflight induced translocation of sarcolemmal nitric oxide synthase-1 (NOS1 into the cytosol in soleus but not in the fast-twitch extensor digitorum longus (EDL muscle. Most of the sarcolemmal ion channel subunits were up-regulated, more in soleus than EDL, whereas Ca(2+-activated K(+ channels were down-regulated, consistent with the phenotype transition. Gene expression of the atrophy-related ubiquitin-ligases was up-regulated in both spaceflown soleus and EDL muscles, whereas autophagy genes were in the control range. Muscle-specific IGF-1 and interleukin-6 were down-regulated in soleus but up-regulated in EDL. Also, various stress-related genes were up-regulated in spaceflown EDL, not in soleus. Altogether, these results suggest that EDL muscle may resist to microgravity-induced atrophy by activating compensatory and protective pathways. Our study shows the extended sensitivity of antigravity soleus muscle after prolonged exposition to microgravity, suggests possible mechanisms accounting for the resistance of EDL, and individuates some molecular targets for the development of countermeasures.

  11. Not just quantity: gluteus maximus muscle characteristics in able-bodied and SCI individuals--implications for tissue viability.

    Science.gov (United States)

    Wu, Gary A; Bogie, Kath M

    2013-08-01

    Some individuals with spinal cord injury (SCI) remain pressure ulcer (PU) free whilst others experience a recurring cycle of tissue breakdown. Detailed analysis of gluteal muscle characteristics may provide insights to local tissue viability variability. The study hypothesis was that SCI individuals have altered muscle composition compared to able-bodied (AB). Ten AB and ten SCI received a supine pelvic CT scan, with contrast. Cross-sectional area (CSA) and overall muscle volume were derived using image analysis. Gluteal muscle tissue type was classified at the S2/S3 sacral vertebrae midpoint, the superior greater trochanters margin (GT) and the inferior ischial tuberosities margin (IT) using the linear transformation Hounsfield Unit scale. SCI gluteal CSA was less than for AB throughout the muscle, with the greatest relative atrophy at the IT (48%). Average AB gluteal volume was nearly double SCI. Eight SCI had over 20% infiltrative adipose tissue, three with over 50%. SCI gluteal CSA and intramuscular fat infiltration were significantly negatively correlated (p SCI IT axial slices showed less lean muscle and higher intramuscular fat infiltration than more proximally (p SCI gluteal muscle characteristics were indicative of impaired tissue viability. SCI disuse muscle atrophy was anticipated; the analytic approach further indicated that intramuscular atrophy was not uniform. SCI muscle composition showed increased proportions of both low density muscle and adipose tissue. CT scan with contrast is effective for gluteal muscle characterization. This assessment technique may contribute to determination of personalized risk for PU development and other secondary complications. Published by Elsevier Ltd.

  12. Childhood optic atrophy.

    Science.gov (United States)

    Mudgil, A V; Repka, M X

    2000-02-01

    To determine the causes, and relative incidence of the common causes, of optic nerve atrophy in children under 10 years old and to compare prevalent aetiologies with those given in previous studies. The Wilmer Information System database was searched to identify all children, diagnosed between 1987 and 1997 with optic atrophy, who were under 10 years old at diagnosis. The medical records of these children were reviewed retrospectively A total of 272 children were identified, Complications from premature birth were the most frequent aetiology of optic atrophy (n = 44, 16%); 68% of these premature infants having a history of intraventricular haemorrhage. Tumour was the second most common aetiology (n = 40, 15%). The most frequent tumour was pilocytic astrocytoma (50%), followed by craniopharyngioma (17%). Hydrocephalus, unrelated to tumour, was the third most common aetiology (n = 26, 10%). In 114 cases (42%), the cause of optic atrophy became manifest in the perinatal period and/or could be attributed to adverse events in utero. A cause was not determined in 4% of cases. In the last decade, prematurity and hydrocephalus appear to have become important causes of optic atrophy in childhood. This trend is probably the result of improved survival of infants with extremely low birth weight.

  13. Mouse Plantar Flexor Muscle Size and Strength After Inactivity and Training

    Science.gov (United States)

    2010-07-01

    atrophy and weakness as a function of the intensity of the train- ing ( 15 ). Although the hind limb suspension resulted in loss of muscle mass in...Muscle Biology Laboratory, Department of Health and Kinesiology , Texas A&M University, College Station, TX, and Gordon L. Warren, Ph.D., Division of

  14. Regulation of skeletal muscle oxidative capacity and muscle mass by SIRT3.

    Directory of Open Access Journals (Sweden)

    Ligen Lin

    Full Text Available We have previously reported that the expression of mitochondrial deacetylase SIRT3 is high in the slow oxidative muscle and that the expression of muscle SIRT3 level is increased by dietary restriction or exercise training. To explore the function of SIRT3 in skeletal muscle, we report here the establishment of a transgenic mouse model with muscle-specific expression of the murine SIRT3 short isoform (SIRT3M3. Calorimetry study revealed that the transgenic mice had increased energy expenditure and lower respiratory exchange rate (RER, indicating a shift towards lipid oxidation for fuel usage, compared to control mice. The transgenic mice exhibited better exercise performance on treadmills, running 45% further than control animals. Moreover, the transgenic mice displayed higher proportion of slow oxidative muscle fibers, with increased muscle AMPK activation and PPARδ expression, both of which are known regulators promoting type I muscle fiber specification. Surprisingly, transgenic expression of SIRT3M3 reduced muscle mass up to 30%, likely through an up-regulation of FOXO1 transcription factor and its downstream atrophy gene MuRF-1. In summary, these results suggest that SIRT3 regulates the formation of oxidative muscle fiber, improves muscle metabolic function, and reduces muscle mass, changes that mimic the effects of caloric restriction.

  15. Elevated interstitial fluid volume in rat soleus muscles by hindlimb unweighting

    DEFF Research Database (Denmark)

    Kandarian, S C; Boushel, Robert Christopher; Schulte, Lars

    1991-01-01

    ) by tail suspension. Soleus muscles were studied after 28 days and compared with those from five age-matched control (C) rats. Interstitial fluid volume ([3H]inulin space) and maximum tetanic tension (Po) were measured in vitro at 25 degrees C. Soleus muscles atrophied 58% because of unweighting (C = 147...

  16. The complex of PAMAM-OH dendrimer with Angiotensin (1–7 prevented the disuse-induced skeletal muscle atrophy in mice

    Directory of Open Access Journals (Sweden)

    Márquez-Miranda V

    2017-03-01

    Full Text Available Valeria Márquez-Miranda,1,2,* Johanna Abrigo,3,4,* Juan Carlos Rivera,3,4 Ingrid Araya-Durán,1 Javier Aravena,3,4 Felipe Simon,3,4 Nicolás Pacheco,1 Fernando Danilo González-Nilo,1,2,5 Claudio Cabello-Verrugio3,4 1Center for Bioinformatics and Integrative Biology (CBIB, Facultad de Ciencias Biologicas, Universidad Andres Bello, Santiago, 2Fundación Fraunhofer Chile Research, Las Condes, 3Departamento de Ciencias Biologicas, Facultad de Ciencias Biologicas & Facultad de Medicina, Universidad Andres Bello, 4Millennium Institute on Immunology and Immunotherapy, Santiago, 5Centro Interdisciplinario de Neurociencia de Valparaíso, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, Chile *These authors contributed equally to this work Abstract: Angiotensin (1–7 (Ang-(1–7 is a bioactive heptapeptide with a short half-life and has beneficial effects in several tissues – among them, skeletal muscle – by preventing muscle atrophy. Dendrimers are promising vehicles for the protection and transport of numerous bioactive molecules. This work explored the use of a neutral, non-cytotoxic hydroxyl-terminated poly(amidoamine (PAMAM-OH dendrimer as an Ang-(1–7 carrier. Bioinformatics analysis showed that the Ang-(1–7-binding capacity of the dendrimer presented a 2:1 molar ratio. Molecular dynamics simulation analysis revealed the capacity of neutral PAMAM-OH to protect Ang-(1–7 and form stable complexes. The peptide coverage ability of the dendrimer was between ~50% and 65%. Furthermore, an electrophoretic mobility shift assay demonstrated that neutral PAMAM-OH effectively bonded peptides. Experimental results showed that the Ang-(1–7/PAMAM-OH complex, but not Ang-(1–7 alone, had an anti-atrophic effect when administered intraperitoneally, as evaluated by muscle strength, fiber diameter, myofibrillar protein levels, and atrogin-1 and MuRF-1 expressions. The results of the Ang-(1–7/PAMAM-OH complex being intraperitoneally

  17. Opaque iris claw lens in a phakic eye to correct acquired diplopia

    NARCIS (Netherlands)

    Landesz, M; Worst, JGF; Rij, GV; Houtman, WA

    1997-01-01

    A 25-year-old man had diplopia caused by abducens nerve paresis on both sides after cranial injury. Because of the patient's reports of persistent diplopia after surgical correction, a specially manufactured, tinted iris claw lens was implanted in the left eye, with the crystalline lens in situ.

  18. Computed tomography in alcoholic cerebellar atrophy

    Energy Technology Data Exchange (ETDEWEB)

    Haubek, A; Lee, K [Hvidovre Hospital Copenhagen (Denmark). Dept. of Radiology; Municipal Hospital, Copenhagen (Denmark). Dept. of Neurology)

    1979-01-01

    This is a controlled CT evaluation of the infratentorial region in 41 male alcoholics under age 35. Criteria for the presence of atrophy are outlined. Twelve patients had cerebellar atrophy. Vermian atrophy was present in all. Atrophy of the cerebellar hemispheres was demonstrated in eight patients as well. The results are statistically significant when compared to an age-matched group of 40 non-alcoholic males among whom two cases of vermian atrophy were found. There were clinical signs of alcoholic cerebellar atrophy in one patient only. The disparity between the clinical and the radiological data are discussed with reference to previous pneumoencephalographic findings. (orig.) 891 AJ/orig. 892 MKO.

  19. The Impact of Muscle Disuse on Muscle Atrophy in Severely Burned Rats

    Science.gov (United States)

    2010-12-01

    fascia around the opened wound were retracted to make a reservoir to hold warm mineral oil to maintain the temperature between 36.5°C to 37.5°C monitored...EDL) as the representative fast-twitch muscle. The EDL is a dorsi flexor, while the PL is a planter flexor. It is possible, as with HLU, plantar

  20. Catabolic signaling pathways, atrogenes, and ubiquitinated proteins are regulated by the nutritional status in the muscle of the fine flounder.

    Directory of Open Access Journals (Sweden)

    Eduardo N Fuentes

    Full Text Available A description of the intracellular mechanisms that modulate skeletal muscle atrophy in early vertebrates is still lacking. In this context, we used the fine flounder, a unique and intriguing fish model, which exhibits remarkably slow growth due to low production of muscle-derived IGF-I, a key growth factor that has been widely acknowledged to prevent and revert muscle atrophy. Key components of the atrophy system were examined in this species using a detailed time-course of sampling points, including two contrasting nutritional periods. Under basal conditions high amounts of the atrogenes MuRF-1 and Atrogin-1 were observed. During fasting, the activation of the P38/MAPK and Akt/FoxO signaling pathways decreased; whereas, the activation of the IκBα/NFκB pathway increased. These changes in signal transduction activation were concomitant with a strong increase in MuRF-1, Atrogin-1, and protein ubiquitination. During short-term refeeding, the P38/MAPK and Akt/FoxO signaling pathways were strongly activated, whereas the activation of the IκBα/NFκB pathway decreased significantly. The expression of both atrogenes, as well as the ubiquitination of proteins, dropped significantly during the first hour of refeeding, indicating a strong anti-atrophic condition during the onset of refeeding. During long-term refeeding, Akt remained activated at higher than basal levels until the end of refeeding, and Atrogin-1 expression remained significantly lower during this period. This study shows that the components of the atrophy system in skeletal muscle appeared early in the evolution of vertebrates and some mechanisms have been conserved, whereas others have not. These results represent an important achievement for the area of fish muscle physiology, showing an integrative view of the atrophy system in a non-mammalian species and contributing to novel insights on the molecular basis of muscle growth regulation in earlier vertebrates.

  1. Consensus Definition for Atrophy Associated with Age-Related Macular Degeneration on OCT: Classification of Atrophy Report 3.

    Science.gov (United States)

    Sadda, Srinivas R; Guymer, Robyn; Holz, Frank G; Schmitz-Valckenberg, Steffen; Curcio, Christine A; Bird, Alan C; Blodi, Barbara A; Bottoni, Ferdinando; Chakravarthy, Usha; Chew, Emily Y; Csaky, Karl; Danis, Ronald P; Fleckenstein, Monika; Freund, K Bailey; Grunwald, Juan; Hoyng, Carel B; Jaffe, Glenn J; Liakopoulos, Sandra; Monés, Jordi M; Pauleikhoff, Daniel; Rosenfeld, Philip J; Sarraf, David; Spaide, Richard F; Tadayoni, Ramin; Tufail, Adnan; Wolf, Sebastian; Staurenghi, Giovanni

    2018-04-01

    To develop consensus terminology and criteria for defining atrophy based on OCT findings in the setting of age-related macular degeneration (AMD). Consensus meeting. Panel of retina specialists, image reading center experts, retinal histologists, and optics engineers. As part of the Classification of Atrophy Meetings (CAM) program, an international group of experts surveyed the existing literature, performed a masked analysis of longitudinal multimodal imaging for a series of eyes with AMD, and reviewed the results of this analysis to define areas of agreement and disagreement. Through consensus discussions at 3 meetings over 12 months, a classification system based on OCT was proposed for atrophy secondary to AMD. Specific criteria were defined to establish the presence of atrophy. A consensus classification system for atrophy and OCT-based criteria to identify atrophy. OCT was proposed as the reference standard or base imaging method to diagnose and stage atrophy. Other methods, including fundus autofluorescence, near-infrared reflectance, and color imaging, provided complementary and confirmatory information. Recognizing that photoreceptor atrophy can occur without retinal pigment epithelium (RPE) atrophy and that atrophy can undergo an evolution of different stages, 4 terms and histologic candidates were proposed: complete RPE and outer retinal atrophy (cRORA), incomplete RPE and outer retinal atrophy, complete outer retinal atrophy, and incomplete outer retinal atrophy. Specific OCT criteria to diagnose cRORA were proposed: (1) a region of hypertransmission of at least 250 μm in diameter, (2) a zone of attenuation or disruption of the RPE of at least 250 μm in diameter, (3) evidence of overlying photoreceptor degeneration, and (4) absence of scrolled RPE or other signs of an RPE tear. A classification system and criteria for OCT-defined atrophy in the setting of AMD has been proposed based on an international consensus. This classification is a more complete

  2. Bed rest attenuates sympathetic and pressor responses to isometric exercise in antigravity leg muscles in humans.

    Science.gov (United States)

    Kamiya, Atsunori; Michikami, Daisaku; Shiozawa, Tomoki; Iwase, Satoshi; Hayano, Junichiro; Kawada, Toru; Sunagawa, Kenji; Mano, Tadaaki

    2004-05-01

    Although spaceflight and bed rest are known to cause muscular atrophy in the antigravity muscles of the legs, the changes in sympathetic and cardiovascular responses to exercises using the atrophied muscles remain unknown. We hypothesized that bed rest would augment sympathetic responses to isometric exercise using antigravity leg muscles in humans. Ten healthy male volunteers were subjected to 14-day 6 degrees head-down bed rest. Before and after bed rest, they performed isometric exercises using leg (plantar flexion) and forearm (handgrip) muscles, followed by 2-min postexercise muscle ischemia (PEMI) that continues to stimulate the muscle metaboreflex. These exercises were sustained to fatigue. We measured muscle sympathetic nerve activity (MSNA) in the contralateral resting leg by microneurography. In both pre- and post-bed-rest exercise tests, exercise intensities were set at 30 and 70% of the maximum voluntary force measured before bed rest. Bed rest attenuated the increase in MSNA in response to fatiguing plantar flexion by approximately 70% at both exercise intensities (both P antigravity leg muscles.

  3. The potential for using red claw crayfish and hybrid African catfish as ...

    African Journals Online (AJOL)

    The potential of red claw crayfish and hybrid African catfish (Clarias gariepinus and Clarias ngamensis) as predators for Schistosoma host snails was evaluated in 2014 by monitoring the consumption of snails by crayfish and catfish in experimental tanks over time under laboratory conditions. After 15 days, both crayfish and ...

  4. Neer Award 2016: reduced muscle degeneration and decreased fatty infiltration after rotator cuff tear in a poly(ADP-ribose) polymerase 1 (PARP-1) knock-out mouse model.

    Science.gov (United States)

    Kuenzler, Michael B; Nuss, Katja; Karol, Agnieszka; Schär, Michael O; Hottiger, Michael; Raniga, Sumit; Kenkel, David; von Rechenberg, Brigitte; Zumstein, Matthias A

    2017-05-01

    Disturbed muscular architecture, atrophy, and fatty infiltration remain irreversible in chronic rotator cuff tears even after repair. Poly (adenosine 5'-diphosphate-ribose) polymerase 1 (PARP-1) is a key regulator of inflammation, apoptosis, muscle atrophy, muscle regeneration, and adipocyte development. We hypothesized that the absence of PARP-1 would lead to a reduction in damage to the muscle subsequent to combined tenotomy and neurectomy in a PARP-1 knockout (KO) mouse model. PARP-1 KO and wild-type C57BL/6 (WT group) mice were analyzed at 1, 6, and 12 weeks (total n = 84). In all mice, the supraspinatus and infraspinatus muscles of the left shoulder were detached and denervated. Macroscopic analysis, magnetic resonance imaging, gene expression analysis, immunohistochemistry, and histology were used to assess the differences in PARP-1 KO and WT mice. The muscles in the PARP-1 KO group had significantly less retraction, atrophy, and fatty infiltration after 12 weeks than in the WT group. Gene expression of inflammatory, apoptotic, adipogenic, and muscular atrophy genes was significantly decreased in PARP-1 KO mice in the first 6 weeks. Absence of PARP-1 leads to a reduction in muscular architectural damage, early inflammation, apoptosis, atrophy, and fatty infiltration after combined tenotomy and neurectomy of the rotator cuff muscle. Although the macroscopic reaction to injury is similar in the first 6 weeks, the ability of the muscles to regenerate was much greater in the PARP-1 KO group, leading to a near-normalization of the muscle after 12 weeks. Copyright © 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

  5. Residue depletion of oxytetracycline (OTC) and 4-epi-oxytetracycline (4-epi-OTC) in broiler chicken's claws by liquid chromatography-tandem mass spectrometry (LC-MS/MS).

    Science.gov (United States)

    Cornejo, J; Pokrant, E; Araya, D; Briceño, C; Hidalgo, H; Maddaleno, A; Araya-Jordán, C; San Martin, B

    2017-04-01

    Antibiotics are widely used in poultry production for the treatment of bacterial diseases. However, residues may remain in products and by-products destined for human consumption or animal feeding. The claws of chickens, which are a by-product of the poultry industry, can directly or indirectly enter the food chain as meals destined to feed other productive animals. Thus, it becomes necessary to determine and quantify antimicrobial residues present in this matrix. The objective of the study was to assess the depletion of oxytetracycline (OTC) and its metabolite 4-epi-OTC in broiler chicken's claws. Claws of 32 broilers treated with a therapeutic dosage of 10% OTC during 7 days were analysed. Samples were taken at days 3, 9, 15 and 19 post-treatment. As for the control group, eight broiler chickens were raised under the same conditions. Extraction was carried out through EDTA-McIlvaine buffer, and clean-up employed a SPE C-18 Sep-Pak®. Instrumental analysis was performed through LC-MS/MS. The concentrations of both analytes were determined in claw samples until day 19 post-treatment. Average concentrations were within the LOD (20 μg kg - 1 ) and LOQ (22 µg kg - 1 ) for OTC and 84 μg kg - 1 for 4-epi-OTC. Withdrawal times (WDTs) of 39 days for OTC and 54 days for 4-epi-OTC were established in claws based on 95% confidence. These findings demonstrate that claws can be a source of antimicrobial residue entry into the food chain, since the results showed that OTC and its metabolite can be found in chicken's claws for long periods, even exceeding the average lifespan of a broiler chicken.

  6. Nandrolone reduces activation of Notch signaling in denervated muscle associated with increased Numb expression

    International Nuclear Information System (INIS)

    Liu, Xin-Hua; Yao, Shen; Qiao, Rui-Fang; Levine, Alice C.; Kirschenbaum, Alexander; Pan, Jiangping; Wu, Yong; Qin, Weiping; Bauman, William A.; Cardozo, Christopher P.

    2011-01-01

    Highlights: → Nerve transection increased Notch signaling in paralyzed muscle. → Nandrolone prevented denervation-induced Notch signaling. → Nandrolone induced the expression of an inhibitor of the Notch signaling, Numb. → Reduction of denervation-induced Notch signaling by nandrolone is likely through upregulation of Numb. -- Abstract: Nandrolone, an anabolic steroid, slows denervation-atrophy in rat muscle. The molecular mechanisms responsible for this effect are not well understood. Androgens and anabolic steroids activate Notch signaling in animal models of aging and thereby mitigate sarcopenia. To explore the molecular mechanisms by which nandrolone prevents denervation-atrophy, we investigated the effects of nandrolone on Notch signaling in denervated rat gastrocnemius muscle. Denervation significantly increased Notch activity reflected by elevated levels of nuclear Notch intracellular domain (NICD) and expression of Hey1 (a Notch target gene). Activation was greatest at 7 and 35 days after denervation but remained present at 56 days after denervation. Activation of Notch in denervated muscle was prevented by nandrolone associated with upregulated expression of Numb mRNA and protein. These data demonstrate that denervation activates Notch signaling, and that nandrolone abrogates this response associated with increased expression of Numb, suggesting a potential mechanism by which nandrolone reduces denervation-atrophy.

  7. Nandrolone reduces activation of Notch signaling in denervated muscle associated with increased Numb expression

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Xin-Hua [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Yao, Shen; Qiao, Rui-Fang; Levine, Alice C. [Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Kirschenbaum, Alexander [Department of Urology, Mount Sinai School of Medicine, New York, NY 10029 (United States); Pan, Jiangping; Wu, Yong [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Qin, Weiping [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Bauman, William A. [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Rehabilitation Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Cardozo, Christopher P., E-mail: chris.cardozo@mssm.edu [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Rehabilitation Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States)

    2011-10-14

    Highlights: {yields} Nerve transection increased Notch signaling in paralyzed muscle. {yields} Nandrolone prevented denervation-induced Notch signaling. {yields} Nandrolone induced the expression of an inhibitor of the Notch signaling, Numb. {yields} Reduction of denervation-induced Notch signaling by nandrolone is likely through upregulation of Numb. -- Abstract: Nandrolone, an anabolic steroid, slows denervation-atrophy in rat muscle. The molecular mechanisms responsible for this effect are not well understood. Androgens and anabolic steroids activate Notch signaling in animal models of aging and thereby mitigate sarcopenia. To explore the molecular mechanisms by which nandrolone prevents denervation-atrophy, we investigated the effects of nandrolone on Notch signaling in denervated rat gastrocnemius muscle. Denervation significantly increased Notch activity reflected by elevated levels of nuclear Notch intracellular domain (NICD) and expression of Hey1 (a Notch target gene). Activation was greatest at 7 and 35 days after denervation but remained present at 56 days after denervation. Activation of Notch in denervated muscle was prevented by nandrolone associated with upregulated expression of Numb mRNA and protein. These data demonstrate that denervation activates Notch signaling, and that nandrolone abrogates this response associated with increased expression of Numb, suggesting a potential mechanism by which nandrolone reduces denervation-atrophy.

  8. Magnetic resonance imaging of facial muscles

    Energy Technology Data Exchange (ETDEWEB)

    Farrugia, M.E. [Department of Clinical Neurology, University of Oxford, Radcliffe Infirmary, Oxford (United Kingdom)], E-mail: m.e.farrugia@doctors.org.uk; Bydder, G.M. [Department of Radiology, University of California, San Diego, CA 92103-8226 (United States); Francis, J.M.; Robson, M.D. [OCMR, Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Oxford (United Kingdom)

    2007-11-15

    Facial and tongue muscles are commonly involved in patients with neuromuscular disorders. However, these muscles are not as easily accessible for biopsy and pathological examination as limb muscles. We have previously investigated myasthenia gravis patients with MuSK antibodies for facial and tongue muscle atrophy using different magnetic resonance imaging sequences, including ultrashort echo time techniques and image analysis tools that allowed us to obtain quantitative assessments of facial muscles. This imaging study had shown that facial muscle measurement is possible and that useful information can be obtained using a quantitative approach. In this paper we aim to review in detail the methods that we applied to our study, to enable clinicians to study these muscles within the domain of neuromuscular disease, oncological or head and neck specialties. Quantitative assessment of the facial musculature may be of value in improving the understanding of pathological processes occurring within facial muscles in certain neuromuscular disorders.

  9. Magnetic resonance imaging of facial muscles

    International Nuclear Information System (INIS)

    Farrugia, M.E.; Bydder, G.M.; Francis, J.M.; Robson, M.D.

    2007-01-01

    Facial and tongue muscles are commonly involved in patients with neuromuscular disorders. However, these muscles are not as easily accessible for biopsy and pathological examination as limb muscles. We have previously investigated myasthenia gravis patients with MuSK antibodies for facial and tongue muscle atrophy using different magnetic resonance imaging sequences, including ultrashort echo time techniques and image analysis tools that allowed us to obtain quantitative assessments of facial muscles. This imaging study had shown that facial muscle measurement is possible and that useful information can be obtained using a quantitative approach. In this paper we aim to review in detail the methods that we applied to our study, to enable clinicians to study these muscles within the domain of neuromuscular disease, oncological or head and neck specialties. Quantitative assessment of the facial musculature may be of value in improving the understanding of pathological processes occurring within facial muscles in certain neuromuscular disorders

  10. Influence of Soft or Hard Floors before and after First Calving on Dairy Heifer Locomotion, Claw and Leg Health

    Directory of Open Access Journals (Sweden)

    Christer Bergsten

    2015-08-01

    Full Text Available Claw health, an important dairy cow welfare parameter, may be affected by early-life foot/leg stresses. To investigate this, groups of pregnant heifers were allocated to deep straw bedding (Soft or cubicles (Hard, both with scraped concrete feeding alleys. After the grazing season, they were re-housed in cubicle systems, half on slatted concrete (Hard and half on slatted rubber (Soft alleys. Claw measurements, contact area and pressure distribution claw/flooring, claw disorders and leg lesions were recorded at the start and end of each housing season. Locomotion and leg lesions were also scored monthly after calving. Prevalence of sole haemorrhages was higher among pregnant heifers in cubicles than in deep straw. After calving, first-calvers on Hard floors had higher odds for lameness (OR = 3.6; P < 0.01, sole haemorrhages/ulcers (OR = 2.2; P < 0.05, white-line haemorrhages (OR = 2.8; P < 0.01 and leg lesions (OR = 2.6; P < 0.02 than those on Soft floors. Lowest prevalence and severity of sole and white-line haemorrhages (non-significant in first-calvers was found in those on Soft floors and reared on Hard floors and the highest prevalence and severity on those on Hard floors reared on Soft floors. Soft flooring after calving is of most importance for healthy feet and legs.

  11. Myostatin from the heart: local and systemic actions in cardiac failure and muscle wasting

    Science.gov (United States)

    Breitbart, Astrid; Auger-Messier, Mannix; Molkentin, Jeffery D.

    2011-01-01

    A significant proportion of heart failure patients develop skeletal muscle wasting and cardiac cachexia, which is associated with a very poor prognosis. Recently, myostatin, a cytokine from the transforming growth factor-β (TGF-β) family and a known strong inhibitor of skeletal muscle growth, has been identified as a direct mediator of skeletal muscle atrophy in mice with heart failure. Myostatin is mainly expressed in skeletal muscle, although basal expression is also detectable in heart and adipose tissue. During pathological loading of the heart, the myocardium produces and secretes myostatin into the circulation where it inhibits skeletal muscle growth. Thus, genetic elimination of myostatin from the heart reduces skeletal muscle atrophy in mice with heart failure, whereas transgenic overexpression of myostatin in the heart is capable of inducing muscle wasting. In addition to its endocrine action on skeletal muscle, cardiac myostatin production also modestly inhibits cardiomyocyte growth under certain circumstances, as well as induces cardiac fibrosis and alterations in ventricular function. Interestingly, heart failure patients show elevated myostatin levels in their serum. To therapeutically influence skeletal muscle wasting, direct inhibition of myostatin was shown to positively impact skeletal muscle mass in heart failure, suggesting a promising strategy for the treatment of cardiac cachexia in the future. PMID:21421824

  12. Glucocorticoids enhance muscle endurance and ameliorate Duchenne muscular dystrophy through a defined metabolic program.

    Science.gov (United States)

    Morrison-Nozik, Alexander; Anand, Priti; Zhu, Han; Duan, Qiming; Sabeh, Mohamad; Prosdocimo, Domenick A; Lemieux, Madeleine E; Nordsborg, Nikolai; Russell, Aaron P; MacRae, Calum A; Gerber, Anthony N; Jain, Mukesh K; Haldar, Saptarsi M

    2015-12-08

    Classic physiology studies dating to the 1930s demonstrate that moderate or transient glucocorticoid (GC) exposure improves muscle performance. The ergogenic properties of GCs are further evidenced by their surreptitious use as doping agents by endurance athletes and poorly understood efficacy in Duchenne muscular dystrophy (DMD), a genetic muscle-wasting disease. A defined molecular basis underlying these performance-enhancing properties of GCs in skeletal muscle remains obscure. Here, we demonstrate that ergogenic effects of GCs are mediated by direct induction of the metabolic transcription factor KLF15, defining a downstream pathway distinct from that resulting in GC-related muscle atrophy. Furthermore, we establish that KLF15 deficiency exacerbates dystrophic severity and muscle GC-KLF15 signaling mediates salutary therapeutic effects in the mdx mouse model of DMD. Thus, although glucocorticoid receptor (GR)-mediated transactivation is often associated with muscle atrophy and other adverse effects of pharmacologic GC administration, our data define a distinct GR-induced gene regulatory pathway that contributes to therapeutic effects of GCs in DMD through proergogenic metabolic programming.

  13. [A 34-year-old woman with delayed motor milestones, high arched palate, and proximal muscle weakness].

    Science.gov (United States)

    Yamamoto, T; Kitada, T; Hirasawa, E; Mori, H; Mizuno, Y

    1996-07-01

    We report a right-handed 34-year-old woman with diffuse muscle atrophy. The patient was a full-term infant of uneventful delivery, however, motor milestones were delayed in that neck control was obtained at 10 months of the age and she started to walk unassisted at 2 years of the age. Mental development was normal. She was unable to run with her mates at her kindergarten and she required a handrail when she walk up the stairs. She could not close her mouth completely at the primary school. She was unable to use a straw as a middle school pupil. Recently, she noted difficulty in raising her head from the supine position, and has become unable to walk a long distance. She was admitted to our hospital in September 17, 1994 when she was 34-year-old. On admission, general physical examination revealed that she looked slender weighing 38 kg with 149.5 cm height. She showed a high arched palate, slight scoliosis, and pes equinus. Otherwise general physical examination was unremarkable. Upon neurologic examination, she was alert and well oriented. Cranial nerves were unremarkable except for bilateral facial atrophy and moderate weakness. Her voice was of nasal quality, and swallowing was slightly difficult. No atrophy was noted in the sternocleidomastoid muscle. She showed waddling gait and positive Gowers' sign. Diffuse muscle atrophy was noted and mild to moderate weakness was presented more in the proximal part in both upper and lower extremities, however, deltoid muscles retained normal power. No ataxia was noted. All the deep tendon reflexes were lost. Sensation was intact. Routine laboratory examination was unremarkable. Serum CK was 56 IU/l. Electromyography revealed myogenic changes in the deltoid, biceps, and quadriceps muscles. A diagnostic biopsy was performed in the left biceps brachii muscle. The patient was discussed in the neurologic CPC, and the chief discussant arrived at the conclusion that the patient had nemaline myopathy. Opinions were divided among

  14. Performances in extreme environments: effects of hyper/hypobarism and hypogravity on skeletal muscle

    Directory of Open Access Journals (Sweden)

    Gerardo Bosco

    2010-09-01

    Full Text Available Many environmental factors may affect muscle plasticity but some have exclusive characteristics that allow them to play a key role to maintain the muscle capacity to generate force; these factors are: i the oxygen availability and ii the load applied to muscle fibres. Hyperbarism is a condition that occurs when a man is subjected to pressure increases. To keep the lungs from collapsing, the air is supplied to him under high pressure which exposes the blood in the lungs to high alveolar gas pressures. Under this condition, the PO2 become sufficiently increased, serious disorders may occur, such as modification of oxygen delivery and/or oxygen availability to permit regular muscle contraction. Also altitude hypobaric hypoxia induces modification of muscle capacity to generate work. Prolonged exposure to high altitude leads significant loss in body mass, thigh muscle mass, muscle fiber area and volume density of muscle mitochondria. Spaceflight results in a number of adaptations to skeletal muscle, including atrophy and early muscle fatigue. Muscle atrophy is observed in a wide range of muscles, with the most extensive loss occurring in the legs, because astronauts are no longer needed to support the body's weight. This review will describe the background on these topics suggesting the strategies to correct the specific muscle changes in presence of environmental stresses, such as the alteration in oxygen-derived signaling pathways or the metabolic consequence of microgravity that may indicate rational interventions to maintain muscle mass and function.

  15. Comparison between MRI and 3D-SSP in olivopontocerebellar atrophy and cortical cerebellar atrophy

    International Nuclear Information System (INIS)

    Hamaguchi, Hirotoshi; Kanda, Fumio; Hosaka, Kayo; Fujii, Masahiko; Chihara, Kazuo

    2004-01-01

    We compared images of three-dimensional stereotactic surface projections (3D-SSP) of SPECT with MRI images in spinocerebellar degeneration patients (13 olivopontocerebellar atrophy (OPCA) and 7 cortical cerebellar atrophy (CCA)). We analyzed a brain blood flow pattern with an image of statistics by 123 I-IMP SPECT. In OPCA patients, a blood flow reduction was more remarkable in 3D-SSP than a degree of cerebellar atrophy in MRI. In patients with CCA, the cerebellum showed little blood flow reduction in 3D-SSP despite of apparent atrophy in MRI. Simultaneous examination both MRI and 3D-SSP might be useful for differential diagnosis of spinocerebellar degenerations. (author)

  16. The cell nuclei of skeletal muscle cells are transcriptionally active in hibernating edible dormice

    Directory of Open Access Journals (Sweden)

    Muller Sylviane

    2009-03-01

    Full Text Available Abstract Background Skeletal muscle is able to react in a rapid, dynamic way to metabolic and mechanical stimuli. In particular, exposure to either prolonged starvation or disuse results in muscle atrophy. At variance, in hibernating animals muscle atrophy may be scarce or absent after bouts of hibernation i.e., periods of prolonged (months inactivity and food deprivation, and muscle function is fully preserved at arousal. In this study, myocytes from the quadriceps muscle of euthermic and hibernating edible dormice were investigated by a combination of morphological, morphometrical and immunocytochemical analyses at the light and electron microscopy level. The focus was on cell nuclei and mitochondria, which are highly sensitive markers of changing metabolic rate. Results Findings presented herein demonstrate that: 1 the general histology of the muscle, inclusive of muscle fibre shape and size, and the ratio of fast and slow fibre types are not affected by hibernation; 2 the fine structure of cytoplasmic and nuclear constituents is similar in euthermia and hibernation but for lipid droplets, which accumulate during lethargy; 3 during hibernation, mitochondria are larger in size with longer cristae, and 4 myonuclei maintain the same amount and distribution of transcripts and transcription factors as in euthermia. Conclusion In this study we demonstrate that skeletal muscle cells of the hibernating edible dormouse maintain their structural and functional integrity in full, even after months in the nest. A twofold explanation for that is envisaged: 1 the maintenance, during hibernation, of low-rate nuclear and mitochondrial activity counterbalancing myofibre wasting, 2 the intensive muscle stimulation (shivering during periodic arousals in the nest, which would mimic physical exercise. These two factors would prevent muscle atrophy usually occurring in mammals after prolonged starvation and/or inactivity as a consequence of prevailing catabolism

  17. Electrical stimulation counteracts muscle atrophy associated with aging in humans

    Directory of Open Access Journals (Sweden)

    Helmut Kern

    2013-07-01

    Full Text Available Functional and structural muscle decline is a major problem during aging. Our goal was to improve in old subjects quadriceps m. force and mobility functional performances (stair test, chair rise test, timed up and go test with neuromuscular electrical stimulation (9 weeks, 2-3times/week, 20-30 minutes per session. Furthermore we performed histological and biological molecular analyses of vastus lateralis m. biopsies. Our findings demonstrate that electrical stimulation significantly improved mobility functional performancies and muscle histological characteristics and molecular markers.

  18. New function of the myostatin/activin type I receptor (ALK4) as a mediator of muscle atrophy and muscle regeneration.

    NARCIS (Netherlands)

    Pasteuning-Vuhman, S.; Boertje-van der Meulen, J.; van Putten, M.; Overzier, M.; ten Dijke, P; Kiełbasa, S.M.; Arindrarto, W.; Wolterbeek, R.; Lezhnina, K.V.; Ozerov, I.V.; Aliper, A.M.; Hoogaars, W.; Aartsma-Rus, A; Loomans, C.J.

    Skeletal muscle fibrosis and impaired muscle regeneration are major contributors to muscle wasting in Duchenne muscular dystrophy (DMD). Muscle growth is negatively regulated by myostatin (MSTN) and activins. Blockage of these pathways may improve muscle quality and function in DMD. Antisense

  19. FMAj: a tool for high content analysis of muscle dynamics in Drosophila metamorphosis.

    Science.gov (United States)

    Kuleesha, Yadav; Puah, Wee Choo; Lin, Feng; Wasser, Martin

    2014-01-01

    During metamorphosis in Drosophila melanogaster, larval muscles undergo two different developmental fates; one population is removed by cell death, while the other persistent subset undergoes morphological remodeling and survives to adulthood. Thanks to the ability to perform live imaging of muscle development in transparent pupae and the power of genetics, metamorphosis in Drosophila can be used as a model to study the regulation of skeletal muscle mass. However, time-lapse microscopy generates sizeable image data that require new tools for high throughput image analysis. We performed targeted gene perturbation in muscles and acquired 3D time-series images of muscles in metamorphosis using laser scanning confocal microscopy. To quantify the phenotypic effects of gene perturbations, we designed the Fly Muscle Analysis tool (FMAj) which is based on the ImageJ and MySQL frameworks for image processing and data storage, respectively. The image analysis pipeline of FMAj contains three modules. The first module assists in adding annotations to time-lapse datasets, such as genotypes, experimental parameters and temporal reference points, which are used to compare different datasets. The second module performs segmentation and feature extraction of muscle cells and nuclei. Users can provide annotations to the detected objects, such as muscle identities and anatomical information. The third module performs comparative quantitative analysis of muscle phenotypes. We applied our tool to the phenotypic characterization of two atrophy related genes that were silenced by RNA interference. Reduction of Drosophila Tor (Target of Rapamycin) expression resulted in enhanced atrophy compared to control, while inhibition of the autophagy factor Atg9 caused suppression of atrophy and enlarged muscle fibers of abnormal morphology. FMAj enabled us to monitor the progression of atrophic and hypertrophic phenotypes of individual muscles throughout metamorphosis. We designed a new tool to

  20. FMAj: a tool for high content analysis of muscle dynamics in Drosophila metamorphosis

    Science.gov (United States)

    2014-01-01

    Background During metamorphosis in Drosophila melanogaster, larval muscles undergo two different developmental fates; one population is removed by cell death, while the other persistent subset undergoes morphological remodeling and survives to adulthood. Thanks to the ability to perform live imaging of muscle development in transparent pupae and the power of genetics, metamorphosis in Drosophila can be used as a model to study the regulation of skeletal muscle mass. However, time-lapse microscopy generates sizeable image data that require new tools for high throughput image analysis. Results We performed targeted gene perturbation in muscles and acquired 3D time-series images of muscles in metamorphosis using laser scanning confocal microscopy. To quantify the phenotypic effects of gene perturbations, we designed the Fly Muscle Analysis tool (FMAj) which is based on the ImageJ and MySQL frameworks for image processing and data storage, respectively. The image analysis pipeline of FMAj contains three modules. The first module assists in adding annotations to time-lapse datasets, such as genotypes, experimental parameters and temporal reference points, which are used to compare different datasets. The second module performs segmentation and feature extraction of muscle cells and nuclei. Users can provide annotations to the detected objects, such as muscle identities and anatomical information. The third module performs comparative quantitative analysis of muscle phenotypes. We applied our tool to the phenotypic characterization of two atrophy related genes that were silenced by RNA interference. Reduction of Drosophila Tor (Target of Rapamycin) expression resulted in enhanced atrophy compared to control, while inhibition of the autophagy factor Atg9 caused suppression of atrophy and enlarged muscle fibers of abnormal morphology. FMAj enabled us to monitor the progression of atrophic and hypertrophic phenotypes of individual muscles throughout metamorphosis

  1. Cobalt triggers necrotic cell death and atrophy in skeletal C2C12 myotubes

    International Nuclear Information System (INIS)

    Rovetta, Francesca; Stacchiotti, Alessandra; Faggi, Fiorella; Catalani, Simona; Apostoli, Pietro; Fanzani, Alessandro; Aleo, Maria Francesca

    2013-01-01

    Severe poisoning has recently been diagnosed in humans having hip implants composed of cobalt–chrome alloys due to the release of particulate wear debris on polyethylene and ceramic implants which stimulates macrophagic infiltration and destroys bone and soft tissue, leading to neurological, sensorial and muscular impairments. Consistent with this premise, in this study, we focused on the mechanisms underlying the toxicity of Co(II) ions on skeletal muscle using mouse skeletal C2C12 myotubes as an in vitro model. As detected using propidium iodide incorporation, increasing CoCl 2 doses (from 5 to 200 μM) affected the viability of C2C12 myotubes, mainly by cell necrosis, which was attenuated by necrostatin-1, an inhibitor of the necroptotic branch of the death domain receptor signaling pathway. On the other hand, apoptosis was hardly detectable as supported by the lack of caspase-3 and -8 activation, the latter resulting in only faint activation after exposure to higher CoCl 2 doses for prolonged time points. Furthermore, CoCl 2 treatment resulted in atrophy of the C2C12 myotubes which was characterized by the increased expression of HSP25 and GRP94 stress proteins and other typical 'pro-atrophic molecular hallmarks, such as early activation of the NF-kB pathway and down-regulation of AKT phosphorylation, followed by the activation of the proteasome and autophagy systems. Overall, these results suggested that cobalt may impact skeletal muscle homeostasis as an inducer of cell necrosis and myofiber atrophy. - Highlights: • The effects of cobalt on muscle myofibers in vitro were investigated. • Cobalt treatment mainly causes cell necrosis in skeletal C2C12 myotubes. • Cobalt impacts the PI3K/AKT and NFkB pathways and induces cell stress markers. • Cobalt induces atrophy of C2C12 myotubes through the activation of proteasome and autophagy systems. • Co treatment triggers NF-kB and PI3K/AKT pathways in C2C12 myotubes

  2. Cobalt triggers necrotic cell death and atrophy in skeletal C2C12 myotubes

    Energy Technology Data Exchange (ETDEWEB)

    Rovetta, Francesca [Unit of Biotechnologies, Department of Molecular and Translational Medicine, University of Brescia, Brescia I-25123 (Italy); Interuniversity Institute of Myology (IIM) (Italy); Stacchiotti, Alessandra [Institute of Human Anatomy, Department of Clinical and Experimental Sciences, University of Brescia, Brescia I-25123 (Italy); Faggi, Fiorella [Unit of Biotechnologies, Department of Molecular and Translational Medicine, University of Brescia, Brescia I-25123 (Italy); Interuniversity Institute of Myology (IIM) (Italy); Catalani, Simona; Apostoli, Pietro [Unit of Occupational Health and Industrial Hygiene, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia I-25123 (Italy); Fanzani, Alessandro, E-mail: fanzani@med.unibs.it [Unit of Biotechnologies, Department of Molecular and Translational Medicine, University of Brescia, Brescia I-25123 (Italy); Interuniversity Institute of Myology (IIM) (Italy); Aleo, Maria Francesca, E-mail: aleo@med.unibs.it [Unit of Biotechnologies, Department of Molecular and Translational Medicine, University of Brescia, Brescia I-25123 (Italy); Interuniversity Institute of Myology (IIM) (Italy)

    2013-09-01

    Severe poisoning has recently been diagnosed in humans having hip implants composed of cobalt–chrome alloys due to the release of particulate wear debris on polyethylene and ceramic implants which stimulates macrophagic infiltration and destroys bone and soft tissue, leading to neurological, sensorial and muscular impairments. Consistent with this premise, in this study, we focused on the mechanisms underlying the toxicity of Co(II) ions on skeletal muscle using mouse skeletal C2C12 myotubes as an in vitro model. As detected using propidium iodide incorporation, increasing CoCl{sub 2} doses (from 5 to 200 μM) affected the viability of C2C12 myotubes, mainly by cell necrosis, which was attenuated by necrostatin-1, an inhibitor of the necroptotic branch of the death domain receptor signaling pathway. On the other hand, apoptosis was hardly detectable as supported by the lack of caspase-3 and -8 activation, the latter resulting in only faint activation after exposure to higher CoCl{sub 2} doses for prolonged time points. Furthermore, CoCl{sub 2} treatment resulted in atrophy of the C2C12 myotubes which was characterized by the increased expression of HSP25 and GRP94 stress proteins and other typical 'pro-atrophic molecular hallmarks, such as early activation of the NF-kB pathway and down-regulation of AKT phosphorylation, followed by the activation of the proteasome and autophagy systems. Overall, these results suggested that cobalt may impact skeletal muscle homeostasis as an inducer of cell necrosis and myofiber atrophy. - Highlights: • The effects of cobalt on muscle myofibers in vitro were investigated. • Cobalt treatment mainly causes cell necrosis in skeletal C2C12 myotubes. • Cobalt impacts the PI3K/AKT and NFkB pathways and induces cell stress markers. • Cobalt induces atrophy of C2C12 myotubes through the activation of proteasome and autophagy systems. • Co treatment triggers NF-kB and PI3K/AKT pathways in C2C12 myotubes.

  3. Relation between extent of myostatin depletion and muscle growth in mature mice

    OpenAIRE

    Welle, Stephen; Burgess, Kerri; Thornton, Charles A.; Tawil, Rabi

    2009-01-01

    Myostatin is a negative regulator of muscle growth and fiber size. Changes in myostatin expression might contribute to changes in muscle mass associated with various conditions, and reducing the amount of active myostatin is a potential strategy for preventing or reversing muscle atrophy. The present study was done to determine the extent to which myostatin levels must decline to induce growth of mature muscles. Myostatin expression was reduced by activating Cre recombinase in adult mice with...

  4. Machine learning algorithms to classify spinal muscular atrophy subtypes.

    Science.gov (United States)

    Srivastava, Tuhin; Darras, Basil T; Wu, Jim S; Rutkove, Seward B

    2012-07-24

    The development of better biomarkers for disease assessment remains an ongoing effort across the spectrum of neurologic illnesses. One approach for refining biomarkers is based on the concept of machine learning, in which individual, unrelated biomarkers are simultaneously evaluated. In this cross-sectional study, we assess the possibility of using machine learning, incorporating both quantitative muscle ultrasound (QMU) and electrical impedance myography (EIM) data, for classification of muscles affected by spinal muscular atrophy (SMA). Twenty-one normal subjects, 15 subjects with SMA type 2, and 10 subjects with SMA type 3 underwent EIM and QMU measurements of unilateral biceps, wrist extensors, quadriceps, and tibialis anterior. EIM and QMU parameters were then applied in combination using a support vector machine (SVM), a type of machine learning, in an attempt to accurately categorize 165 individual muscles. For all 3 classification problems, normal vs SMA, normal vs SMA 3, and SMA 2 vs SMA 3, use of SVM provided the greatest accuracy in discrimination, surpassing both EIM and QMU individually. For example, the accuracy, as measured by the receiver operating characteristic area under the curve (ROC-AUC) for the SVM discriminating SMA 2 muscles from SMA 3 muscles was 0.928; in comparison, the ROC-AUCs for EIM and QMU parameters alone were only 0.877 (p < 0.05) and 0.627 (p < 0.05), respectively. Combining EIM and QMU data categorizes individual SMA-affected muscles with very high accuracy. Further investigation of this approach for classifying and for following the progression of neuromuscular illness is warranted.

  5. PHENOBARBITAL AFFECTS THYROID HISTOLOGY AND LARVAL DEVELOPMENT IN THE AFRICAN CLAWED FROG XENOPUS LAEVIS

    Science.gov (United States)

    The abstract highlights our recent study to explore endocrine disrupting effects of phenobarbital in the African clawed frog, Xenopus laevis. In mammals, this chemical is known to induce the biotransforming enzyme UDP-glucuronosyltransferase (UDPGT) resulting in increased thyroid...

  6. Claw Lesions Causing Clinical Lameness in Lactating Holstein Frisian Crossbred Cows

    Directory of Open Access Journals (Sweden)

    Umar Nazir Zahid

    2014-01-01

    Full Text Available The objective of this study was to identify claw lesions causing clinical lameness in lactating Holstein Frisian (HF crossbred cows in dairy cattle. Seventy dairy farmers were interviewed at the monthly meetings of Progressive Dairy Farmers Association of Ludhiana, Punjab, India. Ten dairy farms were randomly selected as per probability proportional to size and a total of 450 lactating HF crossbred cows were taken into the study. All the lactating cows were scored for locomotion and rear leg view index. Trimming was done in all the clinically lame animals (animals with locomotion scores 2 and 3 and equal number of animals selected randomly from those with locomotion scores 0 and 1. Various claw lesions were evaluated in both the groups. There was a significant relationship between locomotion score and rear leg view index to identify lameness. Sole ulcers and white line fissures were the lesions responsible for clinical lameness. Other lesions did not cause clinical lameness but increased the asymmetry in lactating HF crossbred cows. Both locomotion score and rear leg view index could be reliably used to identify clinical lameness in lactating cattle.

  7. Laminitis-like changes in the claws of feedlot cattle.

    Science.gov (United States)

    Greenough, P R; Vermunt, J J; McKinnon, J J; Fathy, F A; Berg, P A; Cohen, R D

    1990-03-01

    The purpose of this study was to observe and quantitate changes in the claws of two groups of feedlot cattle (calves and backgrounded yearlings) fed diets that varied in energy (73.5 or 78.5% TDN) and crude protein (11, 13, 15, 16, 17, or 19%) content. At slaughter, the thickness of sole horn and the prevalence of toe and heel hemorrhages were greater in calves than in yearlings (pcattle before they reach 14 months of age has a deleterious effect on digital health.

  8. The spectrum of muscle histopathologic findings in 42 weak scleroderma patients

    Science.gov (United States)

    Paik, Julie J.; Wigley, Fredrick M.; Lloyd, Thomas E.; Corse, Andrea M.; Casciola-Rosen, Livia; Shah, Ami A.; Boin, Francesco; Hummers, Laura K.; Mammen, Andrew L.

    2015-01-01

    Objective To determine if distinct muscle pathological features exist in scleroderma subjects with weakness. Methods This retrospective study included weak scleroderma subjects with muscle biopsies available for review. Biopsies were systematically assessed for individual pathologic features including inflammation, necrosis, fibrosis, and acute neurogenic atrophy. Based on the aggregate individual features, biopsies were assigned a histopathologic category of polymyositis, dermatomyositis, necrotizing myopathy, non-specific myositis, “acute denervation”, “fibrosis only”, or “other”. Clinical data analyzed included autoantibody profiles, scleroderma subtype and disease duration, Medsger muscle severity scores, creatine kinase (CK), electromyography (EMG), and muscle magnetic resonance imaging (MRI). Results 42 subjects (79% female and 64% diffuse scleroderma) were included in this study. Necrosis (67%), inflammation (48%), acute neurogenic atrophy (48%), and fibrosis (33%) were the most prevalent pathologic features. The presence of fibrosis was strongly associated with anti-PM-Scl antibodies. Histopathologic categories included non-specific myositis (36%), necrotizing myopathy (21%), dermatomyositis (7%), “acute denervation” (7%), “fibrosis only” (7%), and polymyositis (5%). Disease duration of scleroderma at the time of muscle biopsy was shorter in polymyositis than other histopathologic categories. Patients with anti-PM-Scl and Scl-70 antibodies also had a shorter disease duration than those with other auto-antibody profiles. Conclusion Non-specific myositis and necrotizing myopathy were the most common histopathologic categories in weak scleroderma subjects. Surprisingly, nearly half of the subjects studied had histological evidence of acute motor denervation (acute neurogenic atrophy); this has not been previously reported. Taken together, these observations suggest that a variety of pathologic mechanisms may underlie the development of

  9. Lung injury-dependent oxidative status and chymotrypsin-like activity of skeletal muscles in hamsters with experimental emphysema

    Directory of Open Access Journals (Sweden)

    Tonon Jair

    2013-01-01

    Full Text Available Abstract Background Peripheral skeletal muscle is altered in patients suffering from emphysema and chronic obstructive pulmonary disease (COPD. Oxidative stress have been demonstrated to participate on skeletal muscle loss of several states, including disuse atrophy, mechanical ventilation, and chronic diseases. No evidences have demonstrated the occurance in a severity manner. Methods We evaluated body weight, muscle loss, oxidative stress, and chymotrypsin-like proteolytic activity in the gastrocnemius muscle of emphysemic hamsters. The experimental animals had 2 different severities of lung damage from experimental emphysema induced by 20 mg/mL (E20 and 40 mg/mL (E40 papain. Results The severity of emphysema increased significantly in E20 (60.52 ± 2.8, p Conclusions Taken together, the results of the present study suggest that muscle atrophy observed in this model of emphysema is mediated by increased muscle chymotrypsin-like activity, with possible involvement of oxidative stress in a severity-dependent manner.

  10. Monitoring of noble, signal and narrow-clawed crayfish using environmental DNA from freshwater samples

    DEFF Research Database (Denmark)

    Agersnap, Sune; Larsen, William Brenner; Knudsen, Steen Wilhelm

    2017-01-01

    human assisted expansion of non-indigenous signal crayfish Pacifastacus leniusculus that carry and transmit the crayfish plague pathogen. In Denmark, also the non-indigenous narrow-clawed crayfish Astacus leptodactylus has expanded due to anthropogenic activities. Knowledge about crayfish distribution...

  11. Age-related functional changes and susceptibility to eccentric contraction-induced damage in skeletal muscle cell.

    Science.gov (United States)

    Choi, Seung-Jun

    2016-09-01

    Depending upon external loading conditions, skeletal muscles can either shorten, lengthen, or remain at a fixed length as they produce force. Fixed-end or isometric contractions stabilize joints and allow muscles to act as active struts during locomotion. Active muscles dissipate energy when they are lengthened by an external force that exceeds their current force producing capacity. These unaccustomed eccentric activities often lead to muscle weakness, soreness, and inflammation. During aging, the ability to produce force under these conditions is reduced and appears to be due to not only reductions in muscle mass but also to alterations in the basic mechanisms of contraction. These alterations include impairments in the excitation-contraction process, and the action of the cross-bridges. Also, it is well known that age-related skeletal muscle atrophy is characterized by a preferential atrophy of fast fibers, and increased susceptibility to fast muscle fiber when aged muscles are exposed to eccentric contraction followed by the impaired recovery process has been reported. Taken together, the selective loss of fast muscle fiber in aged muscle could be affected by eccentric-induced muscle damage, which has significant implication to identify the etiology of the age-related functional changes. Therefore, in this review the alteration of age-related muscle function and its impact to/of eccentric induced muscle damage and recovery will be addressed in detail.

  12. Age-related functional changes and susceptibility to eccentric contraction-induced damage in skeletal muscle cell

    Directory of Open Access Journals (Sweden)

    Seung-Jun Choi

    2016-09-01

    Full Text Available Depending upon external loading conditions, skeletal muscles can either shorten, lengthen, or remain at a fixed length as they produce force. Fixed-end or isometric contractions stabilize joints and allow muscles to act as active struts during locomotion. Active muscles dissipate energy when they are lengthened by an external force that exceeds their current force producing capacity. These unaccustomed eccentric activities often lead to muscle weakness, soreness, and inflammation. During aging, the ability to produce force under these conditions is reduced and appears to be due to not only reductions in muscle mass but also to alterations in the basic mechanisms of contraction. These alterations include impairments in the excitation–contraction process, and the action of the cross-bridges. Also, it is well known that age-related skeletal muscle atrophy is characterized by a preferential atrophy of fast fibers, and increased susceptibility to fast muscle fiber when aged muscles are exposed to eccentric contraction followed by the impaired recovery process has been reported. Taken together, the selective loss of fast muscle fiber in aged muscle could be affected by eccentric-induced muscle damage, which has significant implication to identify the etiology of the age-related functional changes. Therefore, in this review the alteration of age-related muscle function and its impact to/of eccentric induced muscle damage and recovery will be addressed in detail.

  13. Impaired translocation of GLUT4 results in insulin resistance of atrophic soleus muscle.

    Science.gov (United States)

    Xu, Peng-Tao; Song, Zhen; Zhang, Wen-Cheng; Jiao, Bo; Yu, Zhi-Bin

    2015-01-01

    Whether or not the atrophic skeletal muscle induces insulin resistance and its mechanisms are not resolved now. The antigravity soleus muscle showed a progressive atrophy in 1-week, 2-week, and 4-week tail-suspended rats. Hyperinsulinemic-euglycemic clamp showed that the steady-state glucose infusion rate was lower in 4-week tail-suspended rats than that in the control rats. The glucose uptake rates under insulin- or contraction-stimulation were significantly decreased in 4-week unloaded soleus muscle. The key protein expressions of IRS-1, PI3K, and Akt on the insulin-dependent pathway and of AMPK, ERK, and p38 on the insulin-independent pathway were unchanged in unloaded soleus muscle. The unchanged phosphorylation of Akt and p38 suggested that the activity of two signal pathways was not altered in unloaded soleus muscle. The AS160 and GLUT4 expression on the common downstream pathway also was not changed in unloaded soleus muscle. But the GLUT4 translocation to sarcolemma was inhibited during insulin stimulation in unloaded soleus muscle. The above results suggest that hindlimb unloading in tail-suspended rat induces atrophy in antigravity soleus muscle. The impaired GLUT4 translocation to sarcolemma under insulin stimulation may mediate insulin resistance in unloaded soleus muscle and further affect the insulin sensitivity of whole body in tail-suspended rats.

  14. Impaired Translocation of GLUT4 Results in Insulin Resistance of Atrophic Soleus Muscle

    Directory of Open Access Journals (Sweden)

    Peng-Tao Xu

    2015-01-01

    Full Text Available Whether or not the atrophic skeletal muscle induces insulin resistance and its mechanisms are not resolved now. The antigravity soleus muscle showed a progressive atrophy in 1-week, 2-week, and 4-week tail-suspended rats. Hyperinsulinemic-euglycemic clamp showed that the steady-state glucose infusion rate was lower in 4-week tail-suspended rats than that in the control rats. The glucose uptake rates under insulin- or contraction-stimulation were significantly decreased in 4-week unloaded soleus muscle. The key protein expressions of IRS-1, PI3K, and Akt on the insulin-dependent pathway and of AMPK, ERK, and p38 on the insulin-independent pathway were unchanged in unloaded soleus muscle. The unchanged phosphorylation of Akt and p38 suggested that the activity of two signal pathways was not altered in unloaded soleus muscle. The AS160 and GLUT4 expression on the common downstream pathway also was not changed in unloaded soleus muscle. But the GLUT4 translocation to sarcolemma was inhibited during insulin stimulation in unloaded soleus muscle. The above results suggest that hindlimb unloading in tail-suspended rat induces atrophy in antigravity soleus muscle. The impaired GLUT4 translocation to sarcolemma under insulin stimulation may mediate insulin resistance in unloaded soleus muscle and further affect the insulin sensitivity of whole body in tail-suspended rats.

  15. Biophysics of underwater hearing in the clawed frog, Xenopus laevis

    DEFF Research Database (Denmark)

    Christensen-Dalsgaard, J; Elepfandt, A

    1995-01-01

    Anesthetized clawed frogs (Xenopus laevis) were stimulated with underwater sound and the tympanic disk vibrations were studied using laser vibrometry. The tympanic disk velocities ranged from 0.01 to 0.5 mm/s (at a sound pressure of 2 Pa) in the frequency range of 0.4-4 kHz and were 20-40 dB high...

  16. Coat and claws as new matrices for noninvasive long-term cortisol assessment in dogs from birth up to 30 days of age.

    Science.gov (United States)

    Veronesi, M C; Comin, A; Meloni, T; Faustini, M; Rota, A; Prandi, A

    2015-09-15

    The last stage of fetal development and the neonatal period represent the most critical phases for the mammals' offspring. In the dog, the knowledge about the final intrauterine fetal development and biology, as well as about the neonatal physiology, remains scarce. Hormonal changes occurring in the last intrauterine fetal phase and during the early neonatal age are still not completely clear, probably because of the invasiveness related to the collection of the more common biological matrix, represented by circulating blood. Toward term of pregnancy, during parturition, and after birth, the hypothalamic-pituitary-adrenal axis is a key system regulating several physiological processes, and its activity was previously investigated by blood analysis, considered an invasive procedure providing a single-point measurement. In respect to animal welfare, and for a more correct long-term retrospective investigation, noninvasive hormonal studies were performed firstly on the hair of humans and coat of animals and, more recently, in the nails of human beings. This study was aimed to assess cortisol (COR) in coat and claws of newborn puppies and to evaluate the possible influence of the newborn gender, breed body size, and age on coat and claws COR concentrations. The results obtained from 165 newborn puppies evidenced that coat and claws COR levels were highly correlated each other (P coat and claws COR concentrations (P coat and claws of newborn dogs. Moreover, both matrices appear as useful tools for new, noninvasive, long-term perinatal and neonatal researches also in canine species. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. What's So Special about FGF19-Unique Effects Reported on Skeletal Muscle Mass and Function.

    Science.gov (United States)

    Glass, David J

    2017-08-01

    In a recent study published in Nature Medicine, Benoit et al. (2017) reported unique effects of FGF19 on mouse skeletal muscle: FGF19 induced skeletal muscle hypertrophy and blocked muscle atrophy, acting via FGF receptors and ßKlotho, while a related FGF21 hormone was ineffective. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Effects of flooring and restricted freestall access on behavior and claw health of dairy heifers.

    Science.gov (United States)

    Ouweltjes, W; van der Werf, J T N; Frankena, K; van Leeuwen, J L

    2011-02-01

    Claw health, locomotion, feed intake, milk yield, body weight, activity, and lying and standing behavior of dairy heifers were monitored in a single dairy herd during the first 3 mo after calving. During the first 8 wk after calving, 2 treatments were applied: restricted freestall access by closing the stalls between 2300 h and 0500 h (yes or no) and alley flooring (concrete or rubber topped slatted floors). Apart from treatments, housing was identical. The animals were kept in small groups (n=4 to 6) in adjacent barn pens. Thereafter, the animals were kept in 1 group in a freestall section with concrete slatted floor and unrestricted access to the stalls for 5 wk. All animals were fed the same partial mixed ration. We hypothesized that (1) hard flooring causes high mechanical load of the claws and (2) restricted freestall access causes prolonged standing bouts and reinforced effects of hard flooring on claws. The heifers had only minor claw lesions before first calving, and the prevalence and severity of sole hemorrhages increased during the first 3 mo after calving (from 0.24 ± 0.08 to 1.18 ± 0.14 and from 0.04 ± 0.01 to 0.24 ± 0.02, respectively), particularly in the outer hind claws. Animals kept on rubber alley flooring had lower average hemorrhage scores in wk 9 (0.13 ± 0.03 vs. 0.21 ± 0.03) and wk 14 (0.20 ± 0.03 vs. 0.27 ± 0.03) after calving, had a slower feed intake (3.05 ± 0.14 vs. 3.46 ± 0.14 g/s) and spent more time feeding (7.3 ± 0.3 vs. 6.6 ± 0.3 min/h) than animals kept on hard concrete alley floors. Restricted freestall access resulted in fewer standing bouts per day (14.4 ± 1.0 vs. 17.9 ± 1.0) and more strides per hour (99.8 ± 5.4 vs. 87.2 ± 5.4) without changing overall standing time (15.0 ± 0.3 vs. 14.7 ± 0.3 h/d) and did not affect the occurrence of sole hemorrhages. The animals with no overnight freestall access spent more time standing (55.9 ± 0.9 vs. 35.8 ± 0.9 min/h) and feeding (7.8 ± 0.3 vs. 4.3 ± 0.3 min/h) between

  19. PPARβ/δ regulates glucocorticoid- and sepsis-induced FOXO1 activation and muscle wasting.

    Directory of Open Access Journals (Sweden)

    Estibaliz Castillero

    Full Text Available FOXO1 is involved in glucocorticoid- and sepsis-induced muscle wasting, in part reflecting regulation of atrogin-1 and MuRF1. Mechanisms influencing FOXO1 expression in muscle wasting are poorly understood. We hypothesized that the transcription factor peroxisome proliferator-activated receptor β/δ (PPARβ/δ upregulates muscle FOXO1 expression and activity with a downstream upregulation of atrogin-1 and MuRF1 expression during sepsis and glucocorticoid treatment and that inhibition of PPARβ/δ activity can prevent muscle wasting. We found that activation of PPARβ/δ in cultured myotubes increased FOXO1 activity, atrogin-1 and MuRF1 expression, protein degradation and myotube atrophy. Treatment of myotubes with dexamethasone increased PPARβ/δ expression and activity. Dexamethasone-induced FOXO1 activation and atrogin-1 and MuRF1 expression, protein degradation, and myotube atrophy were inhibited by PPARβ/δ blocker or siRNA. Importantly, muscle wasting induced in rats by dexamethasone or sepsis was prevented by treatment with a PPARβ/δ inhibitor. The present results suggest that PPARβ/δ regulates FOXO1 activation in glucocorticoid- and sepsis-induced muscle wasting and that treatment with a PPARβ/δ inhibitor may ameliorate loss of muscle mass in these conditions.

  20. Proteome-wide Adaptations of Mouse Skeletal Muscles during a Full Month in Space.

    Science.gov (United States)

    Tascher, Georg; Brioche, Thomas; Maes, Pauline; Chopard, Angèle; O'Gorman, Donal; Gauquelin-Koch, Guillemette; Blanc, Stéphane; Bertile, Fabrice

    2017-07-07

    The safety of space flight is challenged by a severe loss of skeletal muscle mass, strength, and endurance that may compromise the health and performance of astronauts. The molecular mechanisms underpinning muscle atrophy and decreased performance have been studied mostly after short duration flights and are still not fully elucidated. By deciphering the muscle proteome changes elicited in mice after a full month aboard the BION-M1 biosatellite, we observed that the antigravity soleus incurred the greatest changes compared with locomotor muscles. Proteomics data notably suggested mitochondrial dysfunction, metabolic and fiber type switching toward glycolytic type II fibers, structural alterations, and calcium signaling-related defects to be the main causes for decreased muscle performance in flown mice. Alterations of the protein balance, mTOR pathway, myogenesis, and apoptosis were expected to contribute to muscle atrophy. Moreover, several signs reflecting alteration of telomere maintenance, oxidative stress, and insulin resistance were found as possible additional deleterious effects. Finally, 8 days of recovery post flight were not sufficient to restore completely flight-induced changes. Thus in-depth proteomics analysis unraveled the complex and multifactorial remodeling of skeletal muscle structure and function during long-term space flight, which should help define combined sets of countermeasures before, during, and after the flight.

  1. Sensorimotor Control of the Shoulder in Professional Volleyball Players with Isolated Infraspinatus Muscle Atrophy.

    Science.gov (United States)

    Contemori, Samuele; Biscarini, Andrea; Botti, Fabio Massimo; Busti, Daniele; Panichi, Roberto; Pettorossi, Vito Enrico

    2017-06-12

    Isolated infraspinatus muscle atrophy (IIMA) only affects the hitting shoulder of overhead-activity athletes, and is caused by suprascapular nerve neuropathy. No study has assessed the static and dynamic stability of the shoulder in overhead professional athletes with IIMA to reveal possible shoulder sensorimotor alterations. To assess the shoulder static stability, dynamic stability, and strength in professional volleyball players with IIMA and in healthy control players. Cross-sectional study. Research laboratory. Twenty-four male professional volleyball players (12 players with diagnosed IIMA and 12 healthy players) recruited from local volleyball teams. Static stability was evaluated with two independent force platforms and dynamic stability was assessed with the "Upper Quarter Y Balance Test". The static stability assessment was conducted in different support (single hand and both hand) and vision (open and closed eyes) conditions. Data from each test were analyzed with ANOVA and paired t-test models, to highlight statistical differences within and between groups. In addition to reduced abduction and external rotation strength, athletes with IIMA consistently demonstrated significant less static (P < 0.001) and dynamic stability (P < 0,001), compared with the contralateral shoulder and with healthy athletes. Closed eyes condition significantly enhanced the static stability deficit of the shoulder with IIMA (P = 0.039 and P = 0.034 for both hand and single hand support, respectively), but had no effect in healthy contralateral and healthy players' shoulders. This study highlights an impairment of the sensorimotor control system of the shoulder with IIMA, which likely results from both proprioceptive and strength deficits. This condition could yield subtle alteration in the functional use of the shoulder and predispose it to acute or overuse injuries. The results of this study may help athletic trainers and physical/physiotherapists to prevent shoulder injuries

  2. Use of various free flaps in progressive hemifacial atrophy.

    Science.gov (United States)

    Baek, Rongmin; Heo, Chanyeong; Kim, Baek-kyu

    2011-11-01

    Romberg disease is an uncommon condition manifested by progressive hemifacial atrophy of the skin, soft tissue, and bone. Facial asymmetry with soft tissue deficiency in Romberg disease causes a significant disability affecting the social life and can bring about many psychological problems. The aim of surgical treatment is cosmetic amelioration of the defect. Several conventional reconstructive procedures have been used for correcting facial asymmetry. They include fat injections, dermal fat grafts, filler injections, cartilage and bone grafts, and pedicled and free flaps. We report our experiences with 11 patients involving 11 free flaps with a minimum 1-year follow-up. All patients were classified as having moderate to severe atrophy. The average age at disease onset was 4.5 years; the average duration of atrophy was 5.2 years. No patients were operated on with a quiescent interval of less than 1 year. The average age at operation was 20.1 years, ranging from 10 to 55 years. Reconstruction was performed using 4 groin dermofat free flaps, 4 latissimus dorsi muscle free flaps, and 3 other perforator flaps. To achieve the finest symmetrical and aesthetic results, several ancillary procedures were performed in 4 patients. These procedures included Le Fort I leveling osteotomy, sagittal split ramus osteotomy, reduction malarplasty and angle plasty, rib and calvarial bone graft, correction of alopecia, and additional fat graft. All patients were satisfied with the results. We believe that a free flap transfer is the requisite treatment modality for severe degree of facial asymmetry in Romberg disease.

  3. Fluoride bioaccumulation and toxic effects on the survival and behavior of the endangered white-clawed crayfish Austropotamobius pallipes (Lereboullet).

    Science.gov (United States)

    Aguirre-Sierra, Arantxa; Alonso, Alvaro; Camargo, Julio A

    2013-08-01

    Laboratory experiments were performed to examine the toxic effects of fluoride (F(-)) on the survival and behavior of white-clawed crayfish (Austropotamobius pallipes). Body fluoride contents (bioaccumulation) of test crayfish were also examined. No significant differences between male and female crayfish regarding mortality, escape (tail-flip) response, and fluoride bioaccumulation were detected. For mortality, 48-, 72-, 96-, 120-, 144-, 168-, and 192-h median lethal concentrations (LC50) were estimated to be 93.0, 55.3, 42.7, 36.5, 32.9, 30.6, and 28.9 mg F(-)/l, respectively. For the escape response, 48-, 72-, 96-, 120-, 144-, 168- and 192-h median effective concentrations (EC50) were estimated to be 18.4, 11.1, 8.6, 7.4, 6.7, 6.2 and 5.9 mg F(-)/l, respectively. Average food consumption in test crayfish tended to decrease with increasing water fluoride concentration with a 192-h lowest-observed effect concentration of 10.7 mg F(-)/l. These results indicate that the escape response was the most sensitive end point to fluoride toxicity followed by food consumption and mortality. Fluoride bioaccumulation in test crayfish increased with increasing water fluoride concentration and exposure time. The exoskeleton accumulated more fluoride than muscle. A comparison of the obtained results with previous data for other freshwater invertebrates shows that white-clawed crayfish are relatively tolerant to fluoride toxicity. We conclude that fluoride pollution in freshwater ecosystems should not be viewed as an important risk factor contributing to the catastrophic decrease of A. pallipes in many European countries. Our results indicate that fluoride bioaccumulation in A. pallipes might be used as a bioindicator of fluoride pollution in freshwater ecosystems where it is present.

  4. Functional overload attenuates plantaris atrophy in tumor-bearing rats

    International Nuclear Information System (INIS)

    Otis, Jeffrey S; Lees, Simon J; Williams, Jay H

    2007-01-01

    Late stage cancer malignancies may result in severe skeletal muscle wasting, fatigue and reduced quality of life. Resistance training may attenuate these derangements in cancer patients, but how this hypertrophic response relates to normal muscle adaptations in healthy subjects is unknown. Here, we determined the effect of resistance training on muscle mass and myosin heavy chain (MHC) isoform composition in plantaris muscles from tumor-bearing (TB) rats. Age- and gender-matched Buffalo rats were used for all studies (n = 6/group). Suspensions of Morris Hepatoma MH7777 cells or normal saline were injected subcutaneously into the dorsum. Six weeks after cell implantation, muscles from TB rats were harvested, weighed and processed for ATP-independent proteasome activity assays. Once tumor-induced atrophy had been established, subgroups of TB rats underwent unilateral, functional overload (FO). Healthy, sham-operated rats served as controls. After six weeks, the extent of plantaris hypertrophy was calculated and MHC isoform compositions were determined by gel electrophoresis. Six weeks of tumor growth reduced body mass and the relative masses of gastrocnemius, plantaris, tibialis anterior, extensor digitorum longus, and diaphragm muscles (p ≤ 0.05). Percent reductions in body mass had a strong, negative correlation to final tumor size (r = -0.78). ATP-independent proteasome activity was increased in plantaris muscles from TB rats (p ≤ 0.05). In healthy rats, functional overload (FO) increased plantaris mass ~44% compared to the contralateral control muscle, and increased the relative percentage of MHC type I and decreased the relative percentage of MHC type IIb compared to the sham-operated controls (p ≤ 0.05). Importantly, plantaris mass was increased ~24% in TB-FO rats and adaptations to MHC isoform composition were consistent with normal, resistance-trained muscles. Despite significant skeletal muscle derangements due to cancer, muscle retains the capacity to

  5. Cerebellar atrophy in epileptic patients

    International Nuclear Information System (INIS)

    Taneva, N.

    1991-01-01

    52 patients with epileptic seizures of different form, frequency and duration who had received long term treatment with anticonvulsive drugs were examined on Siretom 2000, a brain scanner of II generation. 6 standard incisions were made in all patients in the area of cerebellum, side ventricules and high convexity. Additional scanning with an incision width of 5 mm was made when pathological changes were detected. There were found 3 cases of cerebellar atrophy, 3 - cerebral atrophy, 1 - combined atrophy and 4 - with other changes. It was difficult to establish any relation between the rerebellar atrophy and the type of anticonvulsant used because treatment had usually been complex. 1 fig., 1 tab., 4 refs

  6. Prevalence of claw disorders in Dutch dairy cows exposed to several floor systems

    NARCIS (Netherlands)

    Somers, J.G.C.J.; Frankena, K.; Noordhuizen-Stassen, E.N.; Metz, J.H.M.

    2003-01-01

    Claw health was examined in an observational study on Dutch dairy farms with either a slatted floor (SL), slatted floor with manure scraper (SL-SCR), solid concrete floor (SCF), a straw yard (SY), or a zero-grazing feeding system (ZG). Hooves of cows' hind legs were examined for the presence and

  7. Deltoid muscle shape analysis with magnetic resonance imaging in patients with chronic rotator cuff tears.

    Science.gov (United States)

    Meyer, Dominik C; Rahm, Stefan; Farshad, Mazda; Lajtai, Georg; Wieser, Karl

    2013-08-19

    It seems appropriate to assume, that for a full and strong global shoulder function a normally innervated and active deltoid muscle is indispensable. We set out to analyse the size and shape of the deltoid muscle on MR-arthrographies, and analyse its influence on shoulder function and its adaption (i.e. atrophy) for reduced shoulder function. The fatty infiltration (Goutallier stages), atrophy (tangent sign) and selective myotendinous retraction of the rotator cuff, as well as the thickness and the area of seven anatomically defined segments of the deltoid muscle were measured on MR-arthrographies and correlated with shoulder function (i.e. active abduction). Included were 116 patients, suffering of a rotator cuff tear with shoulder mobility ranging from pseudoparalysis to free mobility. Kolmogorov-Smirnov test was used to determine the distribution of the data before either Spearman or Pearson correlation and a multiple regression was applied to reveal the correlations. Our developed method for measuring deltoid area and thickness showed to be reproducible with excellent interobserver correlations (r = 0.814-0.982).The analysis of influencing factors on active abduction revealed a weak influence of the amount of SSP tendon (r = -0.25; p muscle retraction (r = -0.27; p muscle infiltration (GFDI: r = -0.36; p muscle shape with the degree of active glenohumeral abduction. Furthermore, long-standing rotator cuff tears did not appear to influence the deltoid shape, i.e. did not lead to muscle atrophy. Our data support that in chronic rotator cuff tears, there seems to be no disadvantage to exhausting conservative treatment and to delay implantation of reverse total shoulder arthroplasty, as the shape of deltoid muscle seems only to be influenced by natural aging, but to be independent of reduced shoulder motion.

  8. Alterations in Muscle Mass and Contractile Phenotype in Response to Unloading Models: Role of Transcriptional/Pretranslational Mechanisms

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    Kenneth M Baldwin

    2013-10-01

    Full Text Available Skeletal muscle is the largest organ system in mammalian organisms providing postural control and movement patterns of varying intensity. Through evolution, skeletal muscle fibers have evolved into three phenotype clusters defined as a muscle unit which consists of all muscle fibers innervated by a single motoneuron linking varying numbers of fibers of similar phenotype. This fundamental organization of the motor unit reflects the fact that there is a remarkable interdependence of gene regulation between the motoneurons and the muscle mainly via activity-dependent mechanisms. These fiber types can be classified via the primary type of myosin heavy chain (MHC gene expressed in the motor unit. Four MHC gene encoded proteins have been identified in striated muscle: slow type I MHC and three fast MHC types, IIa, IIx, and IIb. These MHCs dictate the intrinsic contraction speed of the myofiber with the type I generating the slowest and IIb the fastest contractile speed. Over the last ~35 years, a large body of knowledge suggests that altered loading state cause both fiber atrophy/wasting and a slow to fast shift in the contractile phenotype in the target muscle(s. Hence, this review will examine findings from three different animal models of unloading: 1 space flight (SF, i.e., microgravity; 2 hindlimb suspension (HS, a procedure that chronically eliminates weight bearing of the lower limbs; and 3 spinal cord isolation (SI, a surgical procedure that eliminates neural activation of the motoneurons and associated muscles while maintaining neurotrophic motoneuron-muscle connectivity. The collective findings demonstrate: 1 all three models show a similar pattern of fiber atrophy with differences mainly in the magnitude and kinetics of alteration; 2 transcriptional/pretranslational processes play a major role in both the atrophy process and phenotype shifts; and 3 signaling pathways impacting these alterations appear to be similar in each of the models

  9. Silencing neuronal mutant androgen receptor in a mouse model of spinal and bulbar muscular atrophy.

    Science.gov (United States)

    Sahashi, Kentaro; Katsuno, Masahisa; Hung, Gene; Adachi, Hiroaki; Kondo, Naohide; Nakatsuji, Hideaki; Tohnai, Genki; Iida, Madoka; Bennett, C Frank; Sobue, Gen

    2015-11-01

    Spinal and bulbar muscular atrophy (SBMA), an adult-onset neurodegenerative disease that affects males, results from a CAG triplet repeat/polyglutamine expansions in the androgen receptor (AR) gene. Patients develop progressive muscular weakness and atrophy, and no effective therapy is currently available. The tissue-specific pathogenesis, especially relative pathological contributions between degenerative motor neurons and muscles, remains inconclusive. Though peripheral pathology in skeletal muscle caused by toxic AR protein has been recently reported to play a pivotal role in the pathogenesis of SBMA using mouse models, the role of motor neuron degeneration in SBMA has not been rigorously investigated. Here, we exploited synthetic antisense oligonucleotides to inhibit the RNA levels of mutant AR in the central nervous system (CNS) and explore its therapeutic effects in our SBMA mouse model that harbors a mutant AR gene with 97 CAG expansions and characteristic SBMA-like neurogenic phenotypes. A single intracerebroventricular administration of the antisense oligonucleotides in the presymptomatic phase efficiently suppressed the mutant gene expression in the CNS, and delayed the onset and progression of motor dysfunction, improved body weight gain and survival with the amelioration of neuronal histopathology in motor units such as spinal motor neurons, neuromuscular junctions and skeletal muscle. These findings highlight the importance of the neurotoxicity of mutant AR protein in motor neurons as a therapeutic target. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  10. Tissue-specific models of spinal muscular atrophy confirm a critical role of SMN in motor neurons from embryonic to adult stages.

    Science.gov (United States)

    Laird, Angela S; Mackovski, Nikolce; Rinkwitz, Silke; Becker, Thomas S; Giacomotto, Jean

    2016-05-01

    Spinal muscular atrophy (SMA) is an autosomal recessive disease linked to survival motor neuron (SMN) protein deficiency. While SMN protein is expressed ubiquitously, its deficiency triggers tissue-specific hallmarks, including motor neuron death and muscle atrophy, leading to impaired motor functions and premature death. Here, using stable miR-mediated knockdown technology in zebrafish, we developed the first vertebrate system allowing transgenic spatio-temporal control of the smn1 gene. Using this new model it is now possible to investigate normal and pathogenic SMN function(s) in specific cell types, independently or in synergy with other cell populations. We took advantage of this new system to first test the effect of motor neuron or muscle-specific smn1 silencing. Anti-smn1 miRNA expression in motor neurons, but not in muscles, reproduced SMA hallmarks, including abnormal motor neuron development, poor motor function and premature death. Interestingly, smn1 knockdown in motor neurons also induced severe late-onset phenotypes including scoliosis-like body deformities, weight loss, muscle atrophy and, seen for the first time in zebrafish, reduction in the number of motor neurons, indicating motor neuron degeneration. Taken together, we have developed a new transgenic system allowing spatio-temporal control of smn1 expression in zebrafish, and using this model, we have demonstrated that smn1 silencing in motor neurons alone is sufficient to reproduce SMA hallmarks in zebrafish. It is noteworthy that this research is going beyond SMA as this versatile gene-silencing transgenic system can be used to knockdown any genes of interest, filling the gap in the zebrafish genetic toolbox and opening new avenues to study gene functions in this organism. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  11. Performance of claw-poled PM-stepping motor

    International Nuclear Information System (INIS)

    Liu, C.P.; Jeng, G.R.; Chen, W.C.; Tsai, M.C.; Wu, K.T.; Yao, Y.D.

    2007-01-01

    Present work is to analyze the performance of a permanent-magnetic (PM) stepping motor with claw poles by using the magnetic-circuit simulation technique. In this paper, we calculate the torque characteristics of the motor, such as the detent and the holding torques, and the step-position error by changing the gap between the upper and the lower stators and the staggered angle between the two stators. Through comparison of numerical data with experiment measurements, we found that the detent torque could be effectively reduced by increasing the stator-to-stator gap and further by decreasing the step-position error. Furthermore, the holding torque could be unchanged as the stator assemblage changed; however, it would be degenerated under the condition of low magnetization

  12. High Fat Diet-Induced Skeletal Muscle Wasting Is Decreased by Mesenchymal Stem Cells Administration: Implications on Oxidative Stress, Ubiquitin Proteasome Pathway Activation, and Myonuclear Apoptosis

    Directory of Open Access Journals (Sweden)

    Johanna Abrigo

    2016-01-01

    Full Text Available Obesity can lead to skeletal muscle atrophy, a pathological condition characterized by the loss of strength and muscle mass. A feature of muscle atrophy is a decrease of myofibrillar proteins as a result of ubiquitin proteasome pathway overactivation, as evidenced by increased expression of the muscle-specific ubiquitin ligases atrogin-1 and MuRF-1. Additionally, other mechanisms are related to muscle wasting, including oxidative stress, myonuclear apoptosis, and autophagy. Stem cells are an emerging therapy in the treatment of chronic diseases such as high fat diet-induced obesity. Mesenchymal stem cells (MSCs are a population of self-renewable and undifferentiated cells present in the bone marrow and other mesenchymal tissues of adult individuals. The present study is the first to analyze the effects of systemic MSC administration on high fat diet-induced skeletal muscle atrophy in the tibialis anterior of mice. Treatment with MSCs reduced losses of muscle strength and mass, decreases of fiber diameter and myosin heavy chain protein levels, and fiber type transitions. Underlying these antiatrophic effects, MSC administration also decreased ubiquitin proteasome pathway activation, oxidative stress, and myonuclear apoptosis. These results are the first to indicate that systemically administered MSCs could prevent muscle wasting associated with high fat diet-induced obesity and diabetes.

  13. β-Hydroxy-β-methylbutyrate (HMB normalizes dexamethasone-induced autophagy-lysosomal pathway in skeletal muscle.

    Directory of Open Access Journals (Sweden)

    María D Girón

    Full Text Available Dexamethasone-induced muscle atrophy is due to an increase in protein breakdown and a decrease in protein synthesis, associated with an over-stimulation of the autophagy-lysosomal pathway. These effects are mediated by alterations in IGF-1 and PI3K/Akt signaling. In this study, we have investigated the effects of β-Hydroxy-β-methylbutyrate (HMB on the regulation of autophagy and proteosomal systems. Rats were treated during 21 days with dexamethasone as a model of muscle atrophy. Co-administration of HMB attenuated the effects promoted by dexamethasone. HMB ameliorated the loss in body weight, lean mass and the reduction of the muscle fiber cross-sectional area (shrinkage in gastrocnemius muscle. Consequently, HMB produced an improvement in muscle strength in the dexamethasone-treated rats. To elucidate the molecular mechanisms responsible for these effects, rat L6 myotubes were used. In these cells, HMB significantly attenuated lysosomal proteolysis induced by dexamethasone by normalizing the changes observed in autophagosome formation, LC3 II, p62 and Bnip3 expression after dexamethasone treatment. HMB effects were mediated by an increase in FoxO3a phosphorylation and concomitant decrease in FoxO transcriptional activity. The HMB effect was due to the restoration of Akt signaling diminished by dexamethasone treatment. Moreover, HMB was also involved in the regulation of the activity of ubiquitin and expression of MurF1 and Atrogin-1, components of the proteasome system that are activated or up-regulated by dexamethasone. In conclusion, in vivo and in vitro studies suggest that HMB exerts protective effects against dexamethasone-induced muscle atrophy by normalizing the Akt/FoxO axis that controls autophagy and ubiquitin proteolysis.

  14. β-Hydroxy-β-methylbutyrate (HMB) normalizes dexamethasone-induced autophagy-lysosomal pathway in skeletal muscle.

    Science.gov (United States)

    Girón, María D; Vílchez, Jose D; Shreeram, Sathyavageeswaran; Salto, Rafael; Manzano, Manuel; Cabrera, Elena; Campos, Nefertiti; Edens, Neile K; Rueda, Ricardo; López-Pedrosa, Jose M

    2015-01-01

    Dexamethasone-induced muscle atrophy is due to an increase in protein breakdown and a decrease in protein synthesis, associated with an over-stimulation of the autophagy-lysosomal pathway. These effects are mediated by alterations in IGF-1 and PI3K/Akt signaling. In this study, we have investigated the effects of β-Hydroxy-β-methylbutyrate (HMB) on the regulation of autophagy and proteosomal systems. Rats were treated during 21 days with dexamethasone as a model of muscle atrophy. Co-administration of HMB attenuated the effects promoted by dexamethasone. HMB ameliorated the loss in body weight, lean mass and the reduction of the muscle fiber cross-sectional area (shrinkage) in gastrocnemius muscle. Consequently, HMB produced an improvement in muscle strength in the dexamethasone-treated rats. To elucidate the molecular mechanisms responsible for these effects, rat L6 myotubes were used. In these cells, HMB significantly attenuated lysosomal proteolysis induced by dexamethasone by normalizing the changes observed in autophagosome formation, LC3 II, p62 and Bnip3 expression after dexamethasone treatment. HMB effects were mediated by an increase in FoxO3a phosphorylation and concomitant decrease in FoxO transcriptional activity. The HMB effect was due to the restoration of Akt signaling diminished by dexamethasone treatment. Moreover, HMB was also involved in the regulation of the activity of ubiquitin and expression of MurF1 and Atrogin-1, components of the proteasome system that are activated or up-regulated by dexamethasone. In conclusion, in vivo and in vitro studies suggest that HMB exerts protective effects against dexamethasone-induced muscle atrophy by normalizing the Akt/FoxO axis that controls autophagy and ubiquitin proteolysis.

  15. The effect of neuromuscular electrical stimulation on muscle strength, functional capacity and body composition in haemodialysis patients

    Directory of Open Access Journals (Sweden)

    Vicent Esteve

    2017-01-01

    Conclusions: (1 NMES improved muscle strength, functional capacity and quadriceps muscle composition in our patients. (2 Based on the results obtained, NMES could be a new therapeutic alternative to prevent muscle atrophy and progressive physical deterioration. (3 However, future studies are necessary to establish the potential beneficial effects of NMES in HD patients.

  16. Retropupillary iris-claw intraocular lens for the surgical correction of aphakia in cases with microspherophakia

    Directory of Open Access Journals (Sweden)

    Sameh Mosaad Fouda

    2016-01-01

    Full Text Available Purpose: This study aimed to evaluate the safety and efficacy of retropupillary fixation of an iris-claw intraocular lens (IOL; Verisyse polymethyl methacrylate IOL, Abbott Medical Optics [AMO], Netherlands for the surgical correction of aphakia in microspherophakic eyes without sufficient capsular support. Design: This was a prospective, interventional, noncomparative case series. Methods: This interventional case series comprised 17 eyes of 9 microspherophakic patients. Retropupillary fixation of the Verisyse iris-claw IOL (AMO was performed in all cases. The surgical time was measured. Corrected distance visual acuity, astigmatism, intraocular pressure (IOP, tissue reaction, pigment dispersion, and stability of the IOL were studied 1 day, 3 days, 1 week, 2 weeks, 1 month, and 6 months postoperatively. Results: Eight patients had familial microspherophakia and one patient had Marfan's syndrome. Eighty-two percent of the cases achieved a visual acuity of 0.3 or better. There was no significant postoperative inflammatory reaction. Transient elevation of IOP was recorded in two cases in the 1st week only. One IOL developed disengagement of one of the haptics from the iris and was successfully re-engaged. All the other IOLs were well centered and stable. The mean surgical time was 18.0 ± 4.5 min. Conclusions: Retropupillary fixation of an iris-claw IOL is a safe and effective procedure that provides early visual recovery. It is also a time-saving method for correcting aphakia in microspherophakic eyes without sufficient capsular support.

  17. Effects of Light-Emitting Diode Therapy on Muscle Hypertrophy, Gene Expression, Performance, Damage, and Delayed-Onset Muscle Soreness: Case-control Study with a Pair of Identical Twins.

    Science.gov (United States)

    Ferraresi, Cleber; Bertucci, Danilo; Schiavinato, Josiane; Reiff, Rodrigo; Araújo, Amélia; Panepucci, Rodrigo; Matheucci, Euclides; Cunha, Anderson Ferreira; Arakelian, Vivian Maria; Hamblin, Michael R; Parizotto, Nivaldo; Bagnato, Vanderlei

    2016-10-01

    The aim of this study was to verify how a pair of monozygotic twins would respond to light-emitting diode therapy (LEDT) or placebo combined with a strength-training program during 12 weeks. This case-control study enrolled a pair of male monozygotic twins, allocated randomly to LEDT or placebo therapies. Light-emitting diode therapy or placebo was applied from a flexible light-emitting diode array (λ = 850 nm, total energy = 75 J, t = 15 seconds) to both quadriceps femoris muscles of each twin immediately after each strength training session (3 times/wk for 12 weeks) consisting of leg press and leg extension exercises with load of 80% and 50% of the 1-repetition maximum test, respectively. Muscle biopsies, magnetic resonance imaging, maximal load, and fatigue resistance tests were conducted before and after the training program to assess gene expression, muscle hypertrophy and performance, respectively. Creatine kinase levels in blood and visual analog scale assessed muscle damage and delayed-onset muscle soreness, respectively, during the training program. Compared with placebo, LEDT increased the maximal load in exercise and reduced fatigue, creatine kinase, and visual analog scale. Gene expression analyses showed decreases in markers of inflammation (interleukin 1β) and muscle atrophy (myostatin) with LEDT. Protein synthesis (mammalian target of rapamycin) and oxidative stress defense (SOD2 [mitochondrial superoxide dismutase]) were up-regulated with LEDT, together with increases in thigh muscle hypertrophy. Light-emitting diode therapy can be useful to reduce muscle damage, pain, and atrophy, as well as to increase muscle mass, recovery, and athletic performance in rehabilitation programs and sports medicine.

  18. Muscle histochemistry in chronic alcoholism

    Directory of Open Access Journals (Sweden)

    M. L. Ferraz

    1989-06-01

    Full Text Available Twenty-two chronic acoholic patients were assessed by neurologic examination and muscle biopsy. The patients manifested proximal muscular weakness to a variable extent. One case presented as an acute bout of myopathy, according to the Manual Muscle Test, MMT. The most prominent histologic feature observed was muscle atrophy (95.3% better evidenced through the ATPase stain with the predominance of type II A fibers (71.4%. Lack of the mosaic pattern (type grouping seen in 76% of the cases and an important mitochondrial proliferation with intrasarcoplasmatic lipid accumulation in 63% of the patients. In case of acute presentation of muscle weakness the. pathological substrate is quite different, i.e. presence of myositis mainly interstitial characterized by lymphoplasmocytic infiltrate and several spots of necrosis like Zencker degeneration. Based on histologic criteria, our data suggest that: the main determinant of muscle weakness seen in chronic alcoholic patients is neurogenic in origin (alcoholic polineuropathy; the direct toxic action of ethanol under the skeletal muscle is closely related to the mitochondrial metabolism; the so-called acute alcoholic myopathy has probably viral etiology.

  19. OPA1 deficiency promotes secretion of FGF21 from muscle that prevents obesity and insulin resistance.

    Science.gov (United States)

    Pereira, Renata Oliveira; Tadinada, Satya M; Zasadny, Frederick M; Oliveira, Karen Jesus; Pires, Karla Maria Pereira; Olvera, Angela; Jeffers, Jennifer; Souvenir, Rhonda; Mcglauflin, Rose; Seei, Alec; Funari, Trevor; Sesaki, Hiromi; Potthoff, Matthew J; Adams, Christopher M; Anderson, Ethan J; Abel, E Dale

    2017-07-14

    Mitochondrial dynamics is a conserved process by which mitochondria undergo repeated cycles of fusion and fission, leading to exchange of mitochondrial genetic content, ions, metabolites, and proteins. Here, we examine the role of the mitochondrial fusion protein optic atrophy 1 (OPA1) in differentiated skeletal muscle by reducing OPA1 gene expression in an inducible manner. OPA1 deficiency in young mice results in non-lethal progressive mitochondrial dysfunction and loss of muscle mass. Mutant mice are resistant to age- and diet-induced weight gain and insulin resistance, by mechanisms that involve activation of ER stress and secretion of fibroblast growth factor 21 (FGF21) from skeletal muscle, resulting in increased metabolic rates and improved whole-body insulin sensitivity. OPA1-elicited mitochondrial dysfunction activates an integrated stress response that locally induces muscle atrophy, but via secretion of FGF21 acts distally to modulate whole-body metabolism. © 2017 The Authors.

  20. Behaviour of the Pleistocene marsupial lion deduced from claw marks in a southwestern Australian cave.

    Science.gov (United States)

    Arman, Samuel D; Prideaux, Gavin J

    2016-02-15

    The marsupial lion, Thylacoleo carnifex, was the largest-ever marsupial carnivore, and is one of the most iconic extinct Australian vertebrates. With a highly-specialised dentition, powerful forelimbs and a robust build, its overall morphology is not approached by any other mammal. However, despite >150 years of attention, fundamental aspects of its biology remain unresolved. Here we analyse an assemblage of claw marks preserved on surfaces in a cave and deduce that they were generated by marsupial lions. The distribution and skewed size range of claw marks within the cave elucidate two key aspects of marsupial lion biology: they were excellent climbers and reared young in caves. Scrutiny of >10,000 co-located Pleistocene bones reveals few if any marsupial lion tooth marks, which dovetails with the morphology-based interpretation of the species as a flesh specialist.

  1. Sand Floor for Farmed Blue Foxes: Effects on Claws, Adrenal Cortex Function, Growth and Fur Properties

    Directory of Open Access Journals (Sweden)

    Leena Ahola

    2009-01-01

    Full Text Available Farmed blue foxes (Vulpes lagopus are traditionally housed on mesh floors where they are unable to perform certain species-specific behaviours, such as digging, which may compromise the animals' welfare. This study describes how a possibility to use in-cage sand floor affects welfare-related variables like growth of the claws, adrenal cortex function, and fur properties in juvenile blue foxes. The foxes (N=32 were housed in male-female sibling pairs in an outdoor fur animal shed in cage systems consisting of two traditional fox cages. For the eight male-female sibling pairs of the Control group, there was a mesh floor in both cages of each cage system, whereas for the eight pairs of the Sand group there was a mesh floor in one cage and a 30–40 cm deep earth floor in the other cage. The results show that sand floor is beneficial for the wearing of the claws of foxes. Furthermore, an early experience of sand floor may have positive effects on the foxes' fur development. The results, however, also suggest that there might appear welfare problems observed as disturbed claw growth and increased adrenal cortex activation if foxes that are once provided with clean and unfrozen sand floor are not allowed to enjoy this floor all the time.

  2. Rotator cuff tear reduces muscle fiber specific force production and induces macrophage accumulation and autophagy.

    Science.gov (United States)

    Gumucio, Jonathan P; Davis, Max E; Bradley, Joshua R; Stafford, Patrick L; Schiffman, Corey J; Lynch, Evan B; Claflin, Dennis R; Bedi, Asheesh; Mendias, Christopher L

    2012-12-01

    Full-thickness tears to the rotator cuff can cause severe pain and disability. Untreated tears progress in size and are associated with muscle atrophy and an infiltration of fat to the area, a condition known as "fatty degeneration." To improve the treatment of rotator cuff tears, a greater understanding of the changes in the contractile properties of muscle fibers and the molecular regulation of fatty degeneration is essential. Using a rat model of rotator cuff injury, we measured the force generating capacity of individual muscle fibers and determined changes in muscle fiber type distribution that develop after a full thickness rotator cuff tear. We also measured the expression of mRNA and miRNA transcripts involved in muscle atrophy, lipid accumulation, and matrix synthesis. We hypothesized that a decrease in specific force of rotator cuff muscle fibers, an accumulation of type IIb fibers, and an upregulation in fibrogenic, adipogenic, and inflammatory gene expression occur in torn rotator cuff muscles. Thirty days following rotator cuff tear, we observed a reduction in muscle fiber force production, an induction of fibrogenic, adipogenic, and autophagocytic mRNA and miRNA molecules, and a dramatic accumulation of macrophages in areas of fat accumulation. Copyright © 2012 Orthopaedic Research Society.

  3. Evaluation of hepatic atrophy after transcatheter arterial embolization

    International Nuclear Information System (INIS)

    Chung, Hwan Hoon; Lee, Mee Ran; Oh, Min Cheol; Park, Chul Min; Seol, Hae Young; Cha, In Ho

    1995-01-01

    Hepatic atrophy has been recognized as a complication of hepatic and biliary disease but we have often found it in follow up CT after transcatheter arterial embolization (TACE). The purpose of this study is to evaluate the characteristics of hepatic atrophy after TACE. Of 53 patients who had TACE. We evaluated the relationship between the incidence of hepatic atrophy and the number of TACE, and also evaluated the average number of TACE in patients with hepatic atrophy. Of 20 patients who had received more than average number of TACE for development of hepatic atrophy (2 times with portal vein obstruction, 2.7 times without portal vein obstruction in this study), we evaluated the relationship between the lipiodol uptake pattern of tumor and the incidence of hepatic atrophy. There were 8 cases of hepatic atrophy (3 with portal vein obstruction, 5 without portal vein obstruction), average number for development of hepatic atrophy were 2.5 times. As the number of TACE were increased, the incidence of hepatic atrophy were also increased. Of 20 patients who received more than average number of TACE for development of hepatic atrophy, we noted 6 cases of hepatic atrophy in 11 patients with dense homogenous lipiodol uptake pattern of tumor and noted only 1 case of hepatic atrophy in 9 patient with inhomogenous lipiodol uptake pattern. Hepatic atrophy was one of the CT findings after TACE even without portal vein obstruction. Average number of TACE was 2.5 times and risk factors for development of hepatic atrophy were portal vein obstruction, increased number of TACE, and dense homogenous lipiodol uptake pattern of tumor

  4. Satellite cells in human skeletal muscle plasticity

    Directory of Open Access Journals (Sweden)

    Tim eSnijders

    2015-10-01

    Full Text Available Skeletal muscle satellite cells are considered to play a crucial role in muscle fiber maintenance, repair and remodelling. Our knowledge of the role of satellite cells in muscle fiber adaptation has traditionally relied on in vitro cell and in vivo animal models. Over the past decade, a genuine effort has been made to translate these results to humans under physiological conditions. Findings from in vivo human studies suggest that satellite cells play a key role in skeletal muscle fiber repair/remodelling in response to exercise. Mounting evidence indicates that aging has a profound impact on the regulation of satellite cells in human skeletal muscle. Yet, the precise role of satellite cells in the development of muscle fiber atrophy with age remains unresolved. This review seeks to integrate recent results from in vivo human studies on satellite cell function in muscle fiber repair/remodelling in the wider context of satellite cell biology whose literature is largely based on animal and cell models.

  5. Satellite cells in human skeletal muscle plasticity.

    Science.gov (United States)

    Snijders, Tim; Nederveen, Joshua P; McKay, Bryon R; Joanisse, Sophie; Verdijk, Lex B; van Loon, Luc J C; Parise, Gianni

    2015-01-01

    Skeletal muscle satellite cells are considered to play a crucial role in muscle fiber maintenance, repair and remodeling. Our knowledge of the role of satellite cells in muscle fiber adaptation has traditionally relied on in vitro cell and in vivo animal models. Over the past decade, a genuine effort has been made to translate these results to humans under physiological conditions. Findings from in vivo human studies suggest that satellite cells play a key role in skeletal muscle fiber repair/remodeling in response to exercise. Mounting evidence indicates that aging has a profound impact on the regulation of satellite cells in human skeletal muscle. Yet, the precise role of satellite cells in the development of muscle fiber atrophy with age remains unresolved. This review seeks to integrate recent results from in vivo human studies on satellite cell function in muscle fiber repair/remodeling in the wider context of satellite cell biology whose literature is largely based on animal and cell models.

  6. Oral creatine supplementation attenuates muscle loss caused by limb immobilization: a systematic review

    Directory of Open Access Journals (Sweden)

    Camila Souza Padilha

    Full Text Available Abstract Introduction: Recent studies have pointing creatine supplementation as a promising therapeutic alterna- tive in several diseases, especially myopathies and neurodegenerative disorder. Objective: elucidate the role of creatine supplementation on deleterious effect caused by limb immobilization in humans and rats. Methods: Analyzed articles were searched by three online databases, PubMed, SportDicus e Scielo. After a review and analysis, the studies were included in this review articles on effect of creatine supplementation on skeletal muscle in humans and rat, before, during and after a period of limb immobilization. Results: Studies analyzed demonstrated positive points in use of creatine supplementation as a therapeutic tool to mitigating the deleterious effects of limb immobilization, in humans and rat. Conclusion: The dataset of this literature review allows us to conclude that creatine supplementation may reduce muscle loss and/or assist in the recovery of muscle atrophy caused by immobilization and disuse in rats and humans. Also, we note that further research with better methodological rigor is needed to clarify the mechanisms by which creatine support the recovery of muscle atrophy. Moreover, these effects are positive and promising in the field of muscle rehabilitation, especially after member’s immobilization.

  7. Skeletal muscle mass and exercise performance in stable ambulatory patients with heart failure.

    Science.gov (United States)

    Lang, C C; Chomsky, D B; Rayos, G; Yeoh, T K; Wilson, J R

    1997-01-01

    The purpose of this study was to determine whether skeletal muscle atrophy limits the maximal exercise capacity of stable ambulatory patients with heart failure. Body composition and maximal exercise capacity were measured in 100 stable ambulatory patients with heart failure. Body composition was assessed by using dual-energy X-ray absorption. Peak exercise oxygen consumption (VO2peak) and the anaerobic threshold were measured by using a Naughton treadmill protocol and a Medical Graphics CardioO2 System. VO2peak averaged 13.4 +/- 3.3 ml.min-1.kg-1 or 43 +/- 12% of normal. Lean body mass averaged 52.9 +/- 10.5 kg and leg lean mass 16.5 +/- 3.6 kg. Leg lean mass correlated linearly with VO2peak (r = 0.68, P < 0.01), suggesting that exercise performance is influences by skeletal muscle mass. However, lean body mass was comparable to levels noted in 1,584 normal control subjects, suggesting no decrease in muscle mass. Leg muscle mass was comparable to levels noted in 34 normal control subjects, further supporting this conclusion. These findings suggest that exercise intolerance in stable ambulatory patients with heart failure is not due to skeletal muscle atrophy.

  8. X-linked lethal infantile spinal muscular atrophy: From clinical description to molecular mapping

    Energy Technology Data Exchange (ETDEWEB)

    Baumbach, L.; Schiavi, A. [Univ. of Miami, FL (United States)] [and others

    1994-09-01

    The proximal spinal muscular atrophies (PSMA), one of the most common forms of lower motor neuron disease in children, are characterized by progressive muscle weakness due to loss of anterior horn cells. All three autosomal recessive forms have been mapped to chromosome 5q11.2-11.3, implying an allelic association between these disorders. Recent evidence from our laboratories, as well as others, suggests that a distinct form of lethal neonatal spinal muscular atrophy, associated with early onset contractures, is determined by a gene on the X chromosome. We report our efforts in mapping this disease locus. Our original studies have focused on two unrelated multigenerational families with similar clinical presentations of severe hypotonia, muscle weakness, and a disease course similar to Werdnig Hoffman except for the additional finding of congenital or early onset contractures. Muscle biopsy and/or autopsy were indicative of anterior horn cell loss in affected males. Disease occurrence in each of the families was consistent with an X-linked recessive mode of inheritance. Subsequently, two additional families have been identified, as well as several sporadic male cases. Linkage analysis has been completed in one of these families using highly polymorphic repeats dispersed 10 cM on the X chromosome. Interpretation of results was achieved using an automated data acquisition program. Analysis of over 300 haplotypes generated using PCR-based DNA markers have identified two 16 cM regions on Xp with complete concordance to the disease phenotype. Our currents efforts are focused on the region surrounding the Kallman gene, in attempts to better define a candidate region, as well as analyze possible candidate genes within this region.

  9. Morphometric analysis of somatotropic cells of the adenohypophysis and muscle fibers of the psoas muscle in the process of aging in humans.

    Science.gov (United States)

    Antić, Vladimir M; Stefanović, Natalija; Jovanović, Ivan; Antić, Milorad; Milić, Miroslav; Krstić, Miljan; Kundalić, Braca; Milošević, Verica

    2015-07-01

    The aim of this research was to quantify changes of the adenohypophyseal somatotropes and types 1 and 2 muscle fibers with aging, as well as to establish mutual interactions and correlations with age. Material was samples of hypophysis and psoas major muscle of 27 cadavers of both genders, aged from 30 to 90 years. Adenohypophyseal and psoas major tissue sections were immunohistochemically processed and stained by anti-human growth hormone and anti-fast myosin antibodies, respectively. Morphometric analysis was performed by ImageJ. Results of morphometric analysis showed a significant increase in the somatotrope area, and significant decrease in somatotrope volume density and nucleocytoplasmic ratio with age. Cross-sectional areas of types 1 and 2, and volume density of type 2 muscle fibers decreased significantly with age. One Way ANOVA showed that the latter cited changes in the somatotropes and types 1 and 2 muscle fibers mostly become significant after the age of 70. Significant positive correlation was observed between the area of the somatotropes and volume density of type 2 muscle fibers. A significant negative correlation was detected between the nucleocytoplasmic ratio of the somatotropes and cross-sectional areas of types 1 and 2 muscle fibers. So, it can be concluded that after the age of 70, there is significant loss of the anterior pituitary's somatotropes associated with hypertrophy and possible functional decline of the remained cells. Age-related changes in the somatotropes are correlated with the simultaneous atrophy of type 1, as well as with the atrophy and loss of type 2 muscle fibers. Copyright © 2015 Elsevier GmbH. All rights reserved.

  10. Degree of muscle fatigue in children with chronic juvenile arthritis

    Directory of Open Access Journals (Sweden)

    Sekulić Aleksandra

    2011-01-01

    Full Text Available The aim of our work was to identify gradient of the muscle fatigue of some muscle groups, among children with chronic juvenile arthritis, which are restricted in function by existing limitation in range of motions. Four patients in age of 9,5, with mentioned diagnosis were examined. Healthy subjects, with same ages were control group. Manuel muscle test, range of motion test and EMG examination were performed. Results shown significance difference in degree of muscle fatigue among observed patients, which explain decrease of muscle efficiency and must be taken when intensity of kinesitherapic treatment has to be done. It is concluded that structural changes on locomotory system induce secondary hypertrophy or atrophy of the muscle system and increase of muscle fatigue when activity of certain muscles is performed.

  11. Inflammatory Mechanisms Associated with Skeletal Muscle Sequelae after Stroke: Role of Physical Exercise

    Science.gov (United States)

    Coelho Junior, Hélio José; Gambassi, Bruno Bavaresco; Diniz, Tiego Aparecido; Fernandes, Isabela Maia da Cruz; Caperuto, Érico Chagas; Uchida, Marco Carlos; Lira, Fabio Santos

    2016-01-01

    Inflammatory markers are increased systematically and locally (e.g., skeletal muscle) in stroke patients. Besides being associated with cardiovascular risk factors, proinflammatory cytokines seem to play a key role in muscle atrophy by regulating the pathways involved in this condition. As such, they may cause severe decrease in muscle strength and power, as well as impairment in cardiorespiratory fitness. On the other hand, physical exercise (PE) has been widely suggested as a powerful tool for treating stroke patients, since PE is able to regenerate, even if partially, physical and cognitive functions. However, the mechanisms underlying the beneficial effects of physical exercise in poststroke patients remain poorly understood. Thus, in this study we analyze the candidate mechanisms associated with muscle atrophy in stroke patients, as well as the modulatory effect of inflammation in this condition. Later, we suggest the two strongest anti-inflammatory candidate mechanisms, myokines and the cholinergic anti-inflammatory pathway, which may be activated by physical exercise and may contribute to a decrease in proinflammatory markers of poststroke patients. PMID:27647951

  12. Role of Hoxc genes in the development of the limb integumentary organ (nail, claw, or hoof).

    Science.gov (United States)

    Lasierra, Maria Angeles Ros; Fernández-Guerrero, Marc; Delisle, Lucille; Yakushiji-Kaminatsui, Nayuta; Darbellay, Fabrice; Pérez-Gómez, Rocío; Duboule, Denis

    2018-04-01

    The developing vertebrate limb has long proved as an excellent system for studying the mechanisms involved in pattern formation and morphogenesis and more recently in transcriptional regulation and morphological evolution. To elucidate the stage-specific expression profiles of the components of the developing limb, we have generated the temporal transcriptome of the limb progenitors and of the overlying ectoderm separately. Our study has uncovered a collinear activation of Hoxc genes in the limb ectoderm that we have validated by in situ hybridization. However, while members of the HoxA and HoxD clusters show complex and dynamic patterns of expression during limb development that correlate with the morphology of the different limb segments, no specific function for the HoxC or HoxB clusters has been identified ( 1 - 3 ). To investigate the function of Hoxc genes in the limb ectoderm, we have reexamined the HoxC cluster null mice. Remarkably, and despite exhibiting normal terminal phalanges, these mice didn't form claws (anonychia). Morphological and immunohistochemical analysis identified a failure in the differentiation of the main components of the nail/claw organ. To unravel the transcriptional regulation of Hoxc genes in the limb ectoderm, we used the ATACseq technique. Using this approach, we identified two putative regulatory regions which activity was tested in mouse transgenic enhancer assays. It is currently considered that Hox genes have played a key role in the evolution of morphological traits, probably associated with changes in their regulatory landscapes ( 4 ). Given that the form and size of the distal limb integumentary organ (nail, claw or hoof) correlates with that of the distal phalanx and that the development of hooves was a major innovation in the evolution of a cursorial lifestyle, we are also exploring the possible implication of Hoxc genes in the nail/claw/hoof transition. This abstract is from the Experimental Biology 2018 Meeting. There

  13. Intramuscular pressures in antigravity muscles using gravity-independent, pneumatic hardware.

    Science.gov (United States)

    Macias, Brandon R; Minocha, Ranjeet; Cutuk, Adnan A; Hill, James; Shiau, Jonathon; Hargens, Alan R

    2008-08-01

    Resistive exercise helps prevent muscle atrophy in microgravity, but better exercise equipment is needed. Therefore, the purpose of this study was to determine if a pneumatic, gravity-independent leg-press device (LPD) provides sufficient force to leg musculature. We hypothesized that intramuscular pressure (IMP), a quantitative index of muscle force, is greater in the antigravity superficial posterior and deep posterior compartments than in the non-antigravity anterior compartment during bilateral leg-press exercise. Millar pressure transducers were inserted into the anterior, lateral, superficial posterior, and deep posterior muscle compartments of the left leg of eight healthy subjects (three women, five men). Subjects were supine on the Keiser SX-1, a pneumatic LPD. Then maximal voluntary contraction (MVC) was determined; each subject performed three consecutive voluntary contractions at approximately 18%, 50%, and 100% MVC while continuously measuring IMP. Repeated measures ANOVA were used to determine differences of IMPs between compartments and loads. The magnitudes of IMP (mean +/- SEM) at 18 - 3% (abbreviated approximately 18%), 50%, and 100% MVC in the superficial and deep posterior compartments were significantly greater than that in the anterior compartment during exercise (P antigravity compartments as compared to the non-antigravity compartment. Since antigravity muscles of the leg are contained primarily in the superficial and deep posterior compartments, the LPD may help prevent muscle atrophy associated with microgravity.

  14. Microscopic and immunohistochemical analyses of the claw of the nesting dinosaur, Citipati osmolskae.

    Science.gov (United States)

    Moyer, Alison E; Zheng, Wenxia; Schweitzer, Mary H

    2016-11-16

    One of the most well-recognized Cretaceous fossils is Citipati osmolskae (MPC-D 100/979), an oviraptorid dinosaur discovered in brooding position on a nest of unhatched eggs. The original description refers to a thin lens of white material extending from a manus ungual, which was proposed to represent original keratinous claw sheath that, in life, would have covered it. Here, we test the hypothesis that this exceptional morphological preservation extends to the molecular level. The fossil sheath was compared with that of extant birds, revealing similar morphology and microstructural organization. In living birds, the claw sheath consists primarily of two structural proteins; alpha-keratin, expressed in all vertebrates, and beta-keratin, found only in reptiles and birds (sauropsids). We employed antibodies raised against avian feathers, which comprise almost entirely of beta-keratin, to demonstrate that fossil tissues respond with the same specificity, though less intensity, as those from living birds. Furthermore, we show that calcium chelation greatly increased antibody reactivity, suggesting a role for calcium in the preservation of this fossil material. © 2016 The Author(s).

  15. Effect of salbutamol on innervated and denervated rat soleus muscle

    Directory of Open Access Journals (Sweden)

    ?oic-Vranic T.

    2005-01-01

    Full Text Available The objective of the present investigation was to perform a 14-day time-course study of treatment with salbutamol, a ß2 adrenoceptor agonist, on rat soleus muscle in order to assess fiber type selectivity in the hypertrophic response and fiber type composition. Male Wistar rats were divided into four groups: control (N = 10, treated with salbutamol (N = 30, denervated (N = 30, and treated with salbutamol after denervation (N = 30. Salbutamol was injected intraperitoneally in the rats of the 2nd and 4th groups at a concentration of 0.3 mg/kg twice a day for 2 weeks. The muscles were denervated using the crush method with pean. The animals were sacrificed 3, 6, 9, 12, and 14 days after treatment. Frozen cross-sections of soleus muscle were stained for myosin ATPase, pH 9.4. Cross-sectional area and percent of muscle fibers were analyzed morphometrically by computerized image analysis. Treatment with salbutamol induced hypertrophy of all fiber types and a higher percentage of type II fibers (21% in the healthy rat soleus muscle. Denervation caused marked atrophy of all fibers and conversion from type I to type II muscle fibers. Denervated muscles treated with salbutamol showed a significantly larger cross-sectional area of type I muscle fibers, 28.2% compared to the denervated untreated muscle. Moreover, the number of type I fibers was increased. These results indicate that administration of salbutamol is able to induce changes in cross-sectional area and fiber type distribution in the early phase of treatment. Since denervation-induced atrophy and conversion from type I to type II fibers were improved by salbutamol treatment we propose that salbutamol, like other ß2 adrenoceptor agonists, may have a therapeutic potential in improving the condition of skeletal muscle after denervation.

  16. Bilateral congenital absence of flexor pollicis longus with thumb hypoplasia and thenar atrophy

    International Nuclear Information System (INIS)

    Chaudhary, Vikas; Sehgal, Harsha; Bano, Shahina; Parmar, Pranjali R; Kumar, Sanjay

    2014-01-01

    Congenital absence of flexor pollicis longus with or without associated anomalies of thenar muscles and thumb is of rare occurrence. Inability to flex the interphalangeal joint of the thumb and absent dorsal wrinkles and flexion creases of the thumb are important clues to the diagnosis. Routine radiography and cross-sectional imaging help to confirm and document the condition. This article presents an extremely rare case of bilateral congenital absence of flexor pollicis longus tendon with thumb hypoplasia and thenar atrophy

  17. Correlation of clinical course with MRI findings in olivo-pontocerebellar atrophy and late-cortical cerebellar atrophy

    International Nuclear Information System (INIS)

    Konagaya, Masaaki; Morishita, Shinji; Konagaya, Yoko; Takayanagi, Tetsuya; Iwasaki, Satoru

    1989-01-01

    We quantitatively analyzed 1.5 T MRI in 36 cases of sporadic spinocerebellar degeneration (SCD) and 30 control cases without intracranial lesions, using graphic analyzer. SCD consisted of 21 olivo-ponto-cerebellar atrophy (OPCA) and 15 late cortical cerebellar atrophy (LCCA). There was negative correlation between vermian size and the duration of illness both in OPCA (r=0.8960, p<0.001) and LCCA (r=0.7756, p<0.01), but the progression rate in OPCA was three times greater than that in LCCA. LCCA was suggested the preclinical vermian atrophy by the statistical regression study. In OPCA, the duration of illness also revealed significant correlations with atrophy of ventral pons (r=0.8308, p<0.001) and also cerebellar hemisphere (medial hemiphere; r=0.7278, p<0.001. lateral hemisphere; r=0.6039, p<0.01). OPCA showed diffuse atrophy of cerebellar hemisphere, whereas LCCA showed medial dominant atrophy. OPCA demonstrated significant correlation between the fourth ventricle dilatation and the duration of illness (r=0.6005, p<0.01). A discriminant study significantly separated OPCA, LCCA and control each other by sizes of ventral pons and cerebellar vermis (p<0.001). In T2 weighted MRI, 10 cases out of 14 LCCA did not show hypointensity in dentate nucleus in spite of normal appearance in the other portions usually decreased intensity. The dentate nucleus of OPCA showed a significant atrophy. The insidence of putaminal hypointensity in OPCA was significantly greater than that of control group (ki-quare=6.476, p<0.05). There were no atrophies in red nucleus and tegmentum of midbrain, which indicated minimum involvement in cerebellar efferent system both in OPCA and LCCA. We concluded that the quantitative and qualitative analysis of high field MRI is useful in clinical discrimination between OPCA and LCCA. (author)

  18. GAPDH and β-actin protein decreases with aging, making Stain-Free technology a superior loading control in Western blotting of human skeletal muscle

    DEFF Research Database (Denmark)

    Vigelsø Hansen, Andreas; Dybboe, Rie; Hansen, Christina Neigaard

    2015-01-01

    SF and RP was measured in relation to ageing, muscle atrophy, and different muscle fiber type composition, respectively. A stronger linearity of SF and β-actin compared with GAPDH and α-tubulin was observed. The methodological variation was relatively low in all four methods (4-11%). Protein level...... [β-actin, glyceraldehyde 3-phosphate dehydrogenase (GAPDH), and α-tubulin], as well as TP loaded measured by Stain-Free technology (SF) as normalization tool were tested. This was done using skeletal muscle samples from men subjected to physiological conditions often investigated in applied...... physiology where the intervention has been suggested to impede normalization (ageing, muscle atrophy, and different muscle fiber type composition). The linearity of signal and the methodological variation coefficient was obtained. Furthermore, the inter- and intraindividual variation in signals obtained from...

  19. Genetics Home Reference: optic atrophy type 1

    Science.gov (United States)

    ... Nerve Atrophy Encyclopedia: Visual Acuity Test Health Topic: Color Blindness Health Topic: Optic Nerve Disorders Genetic and Rare ... Disease InfoSearch: Optic atrophy 1 Kids Health: What's Color Blindness? MalaCards: autosomal dominant optic atrophy, classic form Merck ...

  20. Ultrasound Examination Through The Sole Horn On A Weight‐Bearing Claw: Pilot In‐Vitro Study

    DEFF Research Database (Denmark)

    Bach, Kurt; Nielsen, Søren Saxmose; Capion, Nynne

    of a 700 kg heavy Holstein cow The correlation between the thickness of the soft tissue measured with the two different methods was 0.91 (Pearson’s correlation coefficient, Figure 1). Discussion The bottom of the tub could carry the weight of a 700 kg cow. It was possible to scan through the sole horn......Introduction A decrease of the soft tissue thickness in the claw increases the pressure on the corium from the pedal bone and may lead to injuries and claw horn lesions (Ossent & Lischer 1998, Tarlton, et al. 2002). Ultrasonography has been described as a useful method to exam the soft tissue...... the sole horn and through the polyethylene plate respectively had an acceptable correlation. Acknowledgements Thanks to Mogens Nielsen Kreaturslagteri A/S for providing slaughter house legs. References Kofler J, Kubber P, and Henninger W 1999 Ultrasonographic imaging and thickness measurement of the sole...

  1. Human muscle proteins: analysis by two-dimensional electrophoresis

    Energy Technology Data Exchange (ETDEWEB)

    Giometti, C.S.; Danon, M.J.; Anderson, N.G.

    1983-09-01

    Proteins from single frozen sections of human muscle were separated by two-dimensional gel electrophoresis and detected by fluorography or Coomassie Blue staining. The major proteins were identical in different normal muscles obtained from either sex at different ages, and in Duchenne and myotonic dystrophy samples. Congenital myopathy denervation atrophy, polymyositis, and Becker's muscular dystrophy samples, however, showed abnormal myosin light chain compositions, some with a decrease of fast-fiber myosin light chains and others with a decrease of slow-fiber light chains. These protein alterations did not correlate with any specific disease, and may be cause by generalized muscle-fiber damage.

  2. Evolution of vertebrate transient receptor potential vanilloid 3 channels: opposite temperature sensitivity between mammals and western clawed frogs.

    Directory of Open Access Journals (Sweden)

    Shigeru Saito

    2011-04-01

    Full Text Available Transient Receptor Potential (TRP channels serve as temperature receptors in a wide variety of animals and must have played crucial roles in thermal adaptation. The TRP vanilloid (TRPV subfamily contains several temperature receptors with different temperature sensitivities. The TRPV3 channel is known to be highly expressed in skin, where it is activated by warm temperatures and serves as a sensor to detect ambient temperatures near the body temperature of homeothermic animals such as mammals. Here we performed comprehensive comparative analyses of the TRPV subfamily in order to understand the evolutionary process; we identified novel TRPV genes and also characterized the evolutionary flexibility of TRPV3 during vertebrate evolution. We cloned the TRPV3 channel from the western clawed frog Xenopus tropicalis to understand the functional evolution of the TRPV3 channel. The amino acid sequences of the N- and C-terminal regions of the TRPV3 channel were highly diversified from those of other terrestrial vertebrate TRPV3 channels, although central portions were well conserved. In a heterologous expression system, several mammalian TRPV3 agonists did not activate the TRPV3 channel of the western clawed frog. Moreover, the frog TRPV3 channel did not respond to heat stimuli, instead it was activated by cold temperatures. Temperature thresholds for activation were about 16 °C, slightly below the lower temperature limit for the western clawed frog. Given that the TRPV3 channel is expressed in skin, its likely role is to detect noxious cold temperatures. Thus, the western clawed frog and mammals acquired opposite temperature sensitivity of the TRPV3 channel in order to detect environmental temperatures suitable for their respective species, indicating that temperature receptors can dynamically change properties to adapt to different thermal environments during evolution.

  3. Quantitative PCR Analysis of Laryngeal Muscle Fiber Types

    Science.gov (United States)

    Van Daele, Douglas J.

    2010-01-01

    Voice and swallowing dysfunction as a result of recurrent laryngeal nerve paralysis can be improved with vocal fold injections or laryngeal framework surgery. However, denervation atrophy can cause late-term clinical failure. A major determinant of skeletal muscle physiology is myosin heavy chain (MyHC) expression, and previous protein analyses…

  4. FATTY MUSCLE INFILTRATION IN CUFF TEAR: PRE AND POST OPERATIVE EVALUATION BY MRI.

    Science.gov (United States)

    Miyazaki, Alberto Naoki; Santos, Pedro Doneux; da Silva, Luciana Andrade; Sella, Guilherme do Val; Miranda, Eduardo Régis de Alencar Bona; Zampieri, Rodrigo

    2015-01-01

    To evaluate the fatty infiltration and atrophy of the supraespinatus in the pre- and postoperative of a rotator cuff lesion (RCL), by MRI. Ten patients with full-thickness rotator cuff tears who had undergone surgical arthroscopic rotator cuff repair between September and December 2011 were included. This is a prospective study, with analysis and comparison of fatty infiltration and atrophy of the supraespinatus. The occupation ratio was measured using the magic selection tool in Adobe Photoshop CS3((r)) on T1 oblique sagittal Y-view MRI. Through Photoshop, the proportion occupied by the muscle belly regarding its fossae was calculated. There was a statistically significant increase in the muscle ratio (p=0.013) comparing images pre and postoperative, analyzed by the Wilcoxon T test. The proportion of the supraspinal muscle above the pit increases in the immediate postoperative period, probably due to the traction exerted on the tendon at the time of repair. Level of Evidence II, Cohort Study.

  5. Skeletal muscles of hibernating brown bears are unusually resistant to effects of denervation.

    Science.gov (United States)

    Lin, David C; Hershey, John D; Mattoon, John S; Robbins, Charles T

    2012-06-15

    Hibernating bears retain most of their skeletal muscle strength despite drastically reduced weight-bearing activity. Regular neural activation of muscles is a potential mechanism by which muscle atrophy could be limited. However, both mechanical loading and neural activity are usually necessary to maintain muscle size. An alternative mechanism is that the signaling pathways related to the regulation of muscle size could be altered so that neither mechanical nor neural inputs are needed for retaining strength. More specifically, we hypothesized that muscles in hibernating bears are resistant to a severe reduction in neural activation. To test this hypothesis, we unilaterally transected the common peroneal nerve, which innervates ankle flexor muscles, in hibernating and summer-active brown bears (Ursus arctos). In hibernating bears, the long digital extensor (LDE) and cranial tibial (CT) musculotendon masses on the denervated side decreased after 11 weeks post-surgery by 18 ± 11 and 25 ± 10%, respectively, compared with those in the intact side. In contrast, decreases in musculotendon masses of summer-active bears after denervation were 61 ± 4 and 58 ± 5% in the LDE and CT, respectively, and significantly different from those of hibernating bears. The decrease due to denervation in summer-active bears was comparable to that occurring in other mammals. Whole-muscle cross-sectional areas (CSAs) measured from ultrasound images and myofiber CSAs measured from biopsies decreased similarly to musculotendon mass. Thus, hibernating bears alter skeletal muscle catabolic pathways regulated by neural activity, and exploration of these pathways may offer potential solutions for disuse atrophy of muscles.

  6. Factors influencing the attitudes of cattle veterinarians, farmers, and claw trimmers towards the pain associated with the treatment of sole ulcers and the sensitivity to pain of dairy cows.

    Science.gov (United States)

    Becker, Johanna; Reist, Martin; Steiner, Adrian

    2014-04-01

    This study assessed the attitudes of personnel involved in therapeutic claw trimming of dairy cattle in Switzerland towards pain associated with sole ulcers and their treatment. Data from 77 farmers, 32 claw trimmers, and 137 cattle veterinarians were used. A large range of factors were associated with whether the respondents thought that anaesthesia during the treatment of sole ulcers was beneficial; these included year of graduation, work experience, attitude to costs of analgesia, perception of competition between veterinarians and claw trimmers, estimation of pain level associated with treatment, estimated sensitivity of dairy cows to pain, knowledge of the obligation to provide analgesia, and whether the respondent thought lesion size and occurrence of defensive behaviour by the cow were important. Respondents' estimation of the pain level associated with sole ulcer treatment was linked to frequency of therapeutic claw trimming, age, farmers' income, estimated knowledge of the benefits of analgesia, and estimated sensitivity of dairy cows to pain. The latter factor was associated with profession, frequency of therapeutic claw trimming, capability of pain recognition, opinion on the benefits of analgesia, knowledge of the obligation to provide analgesia, and self-estimation of the ability to recognise pain. Improving the knowledge of personnel involved in therapeutic claw trimming with regard to pain in dairy cows and how to alleviate it is crucial if management of pain associated with treatment of sole ulcer and the welfare of lame cows are to be optimised. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Transcriptional profiling of rat skeletal muscle hypertrophy under restriction of blood flow.

    Science.gov (United States)

    Xu, Shouyu; Liu, Xueyun; Chen, Zhenhuang; Li, Gaoquan; Chen, Qin; Zhou, Guoqing; Ma, Ruijie; Yao, Xinmiao; Huang, Xiao

    2016-12-15

    Blood flow restriction (BFR) under low-intensity resistance training (LIRT) can produce similar effects upon muscles to that of high-intensity resistance training (HIRT) while overcoming many of the restrictions to HIRT that occurs in a clinical setting. However, the potential molecular mechanisms of BFR induced muscle hypertrophy remain largely unknown. Here, using a BFR rat model, we aim to better elucidate the mechanisms regulating muscle hypertrophy as induced by BFR and reveal possible clinical therapeutic targets for atrophy cases. We performed genome wide screening with microarray analysis to identify unique differentially expressed genes during rat muscle hypertrophy. We then successfully separated the differentially expressed genes from BRF treated soleus samples by comparing the Affymetrix rat Genome U34 2.0 array with the control. Using qRT-PCR and immunohistochemistry (IHC) we also analyzed other related differentially expressed genes. Results suggested that muscle hypertrophy induced by BFR is essentially regulated by the rate of protein turnover. Specifically, PI3K/AKT and MAPK pathways act as positive regulators in controlling protein synthesis where ubiquitin-proteasome acts as a negative regulator. This represents the first general genome wide level investigation of the gene expression profile in the rat soleus after BFR treatment. This may aid our understanding of the molecular mechanisms regulating and controlling muscle hypertrophy and provide support to the BFR strategies aiming to prevent muscle atrophy in a clinical setting. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Growth Factors and Tension-Induced Skeletal Muscle Growth

    Science.gov (United States)

    Vandenburgh, Herman H.

    1994-01-01

    The project investigated biochemical mechanisms to enhance skeletal muscle growth, and developed a computer based mechanical cell stimulator system. The biochemicals investigated in this study were insulin/(Insulin like Growth Factor) IGF-1 and Steroids. In order to analyze which growth factors are essential for stretch-induced muscle growth in vitro, we developed a defined, serum-free medium in which the differentiated, cultured avian muscle fibers could be maintained for extended periods of time. The defined medium (muscle maintenance medium, MM medium) maintains the nitrogen balance of the myofibers for 3 to 7 days, based on myofiber diameter measurements and myosin heavy chain content. Insulin and IGF-1, but not IGF-2, induced pronounced myofiber hypertrophy when added to this medium. In 5 to 7 days, muscle fiber diameters increase by 71 % to 98% compared to untreated controls. Mechanical stimulation of the avian muscle fibers in MM medium increased the sensitivity of the cells to insulin and IGF-1, based on a leftward shift of the insulin dose/response curve for protein synthesis rates. (54). We developed a ligand binding assay for IGF-1 binding proteins and found that the avian skeletal muscle cultures produced three major species of 31, 36 and 43 kD molecular weight (54) Stretch of the myofibers was found to have no significant effect on the efflux of IGF-1 binding proteins, but addition of exogenous collagen stimulated IGF-1 binding protein production 1.5 to 5 fold. Steroid hormones have a profound effect on muscle protein turnover rates in vivo, with the stress-related glucocorticoids inducing rapid skeletal muscle atrophy while androgenic steroids induce skeletal muscle growth. Exercise in humans and animals reduces the catabolic effects of glucocorticoids and may enhance the anabolic effects of androgenic steroids on skeletal muscle. In our continuing work on the involvement of exogenrus growth factors in stretch-induced avian skeletal muscle growth, we

  9. Expression of interleukin-15 and inflammatory cytokines in skeletal muscles of STZ-induced diabetic rats: effect of resistance exercise training.

    Science.gov (United States)

    Molanouri Shamsi, M; Hassan, Z H; Gharakhanlou, R; Quinn, L S; Azadmanesh, K; Baghersad, L; Isanejad, A; Mahdavi, M

    2014-05-01

    Skeletal muscle atrophy is associated with type-1 diabetes. Skeletal muscle is the source of pro- and anti-inflammatory cytokines that can mediate muscle hypertrophy and atrophy, while resistance exercise can modulate both muscle mass and muscle cytokine expression. This study determined the effects of a 5-week resistance exercise training regimen on the expression of muscle cytokines in healthy and streptozotocin-induced diabetic rats, with special emphasis on interleukin-15 (IL-15), a muscle-derived cytokine proposed to be involved in muscle hypertrophy or responses to stress. Induction of diabetes reduced muscle weight in both the fast flexor hallucis longus (FHL) and slow soleus muscles, while resistance training preserved FHL muscle weight in diabetic rats. IL-15 protein content was increased by training in both FHL and soleus muscles, as well as serum, in normal and diabetic rats. With regard to proinflammatory cytokines, muscle IL-6 levels were increased in diabetic rats, while training decreased muscle IL-6 levels in diabetic rats; training had no effect on FHL muscle IL-6 levels in healthy rats. Also, tumor necrosis factor-alpha (TNF-α) and IL-1β levels were increased by diabetes, but not changed by training. In conclusion, we found that in diabetic rats, resistance training increased muscle and serum IL-15 levels, decreased muscle IL-6 levels, and preserved FHL muscle mass.

  10. Neuroprotective effect of non-viral gene therapy treatment based on tetanus toxin C-fragment in a severe mouse model of Spinal Muscular Atrophy.

    Directory of Open Access Journals (Sweden)

    Sara Olivan Garcia

    2016-08-01

    Full Text Available Spinal muscular atrophy (SMA is a hereditary childhood disease that causes paralysis and progressive degeneration of skeletal muscles and spinal motor neurons. SMA is associated with reduced levels of full-length Survival of Motor Neuron (SMN protein, due to mutations in the Survival of Motor Neuron 1 gene. Nowadays there are no effective therapies available to treat patients with SMA, so our aim was to test whether the non-toxic carboxy-terminal fragment of tetanus toxin heavy chain (TTC, which exhibits neurotrophic properties, might have a therapeutic role or benefit in SMA. In this manuscript, we have demonstrated that TTC enhance the SMN expression in motor neurons in vitro and evaluated the effect of intramuscular injection of TTC-encoding plasmid in the spinal cord and the skeletal muscle of SMNdelta7 mice. For this purpose, we studied the weight and the survival time, as well as, the survival and cell death pathways and muscular atrophy. Our results showed that TTC treatment reduced the expression of autophagy markers (Becn1, Atg5, Lc3 and p62 and pro-apoptotic genes such as Bax and Casp3 in spinal cord. In skeletal muscle, TTC was able to downregulate the expression of the main marker of autophagy, Lc3, to wild type levels and the expression of the apoptosis effector protein, Casp3. Regarding the genes related to muscular atrophy (Ankrd1, Calm1, Col19a1, Fbox32, Mt2, Myod1, NogoA, Pax7, Rrad, and Sln, TTC suggest a compensatory effect for muscle damage response, diminished oxidative stress and modulated calcium homeostasis. These preliminary findings suggest the need for further experiments to depth study the effect of TTC in SMA disease.

  11. Pelvic floor muscle lesions at endoanal MR imaging in female patients with faecal incontinence

    International Nuclear Information System (INIS)

    Terra, Maaike P.; Vervoorn, Inge; Dobben, Annette C.; Stoker, Jaap; Beets-Tan, Regina G.H.; Deutekom, Marije; Bossuyt, Patrick M.M.; Wasser, Martin N.J.M.; Witkamp, Theo D.; Baeten, Cor G.M.I.

    2008-01-01

    To evaluate the frequency and spectrum of lesions of different pelvic floor muscles at endoanal MRI in women with severe faecal incontinence and to study their relation with incontinence severity and manometric findings. In 105 women MRI examinations were evaluated for internal anal sphincter (IAS), external anal sphincter (EAS), puborectal muscle (PM) and levator ani (LA) lesions. The relative contribution of lesions to differences in incontinence severity and manometric findings was studied. IAS (n=59) and EAS (n=61) defects were more common than PM (n=23) and LA (n=26) defects. PM and LA defects presented mainly with IAS and/or EAS defects (isolated n=2 and n=3). EAS atrophy (n=73) was more common than IAS (n=19), PM (n=16) and LA (n=9) atrophy and presented mainly isolated. PM and LA atrophy presented primarily with EAS atrophy (isolated n=3 and n=1). Patients with IAS and EAS lesions had a lower resting and squeeze pressure, respectively; no other associations were found. PM and LA lesions are relatively common in patients with severe faecal incontinence, but the majority of lesions are found in women who also have IAS and/or EAS lesions. Only an association between anal sphincter lesions and manometry was observed. (orig.)

  12. Effects of spinal cord injury-induced changes in muscle activation on foot drag in a computational rat ankle model.

    Science.gov (United States)

    Hillen, Brian K; Jindrich, Devin L; Abbas, James J; Yamaguchi, Gary T; Jung, Ranu

    2015-04-01

    Spinal cord injury (SCI) can lead to changes in muscle activation patterns and atrophy of affected muscles. Moderate levels of SCI are typically associated with foot drag during the swing phase of locomotion. Foot drag is often used to assess locomotor recovery, but the causes remain unclear. We hypothesized that foot drag results from inappropriate muscle coordination preventing flexion at the stance-to-swing transition. To test this hypothesis and to assess the relative contributions of neural and muscular changes on foot drag, we developed a two-dimensional, one degree of freedom ankle musculoskeletal model with gastrocnemius and tibialis anterior muscles. Anatomical data collected from sham-injured and incomplete SCI (iSCI) female Long-Evans rats as well as physiological data from the literature were used to implement an open-loop muscle dynamics model. Muscle insertion point motion was calculated with imposed ankle trajectories from kinematic analysis of treadmill walking in sham-injured and iSCI animals. Relative gastrocnemius deactivation and tibialis anterior activation onset times were varied within physiologically relevant ranges based on simplified locomotor electromyogram profiles. No-atrophy and moderate muscle atrophy as well as normal and injured muscle activation profiles were also simulated. Positive moments coinciding with the transition from stance to swing phase were defined as foot swing and negative moments as foot drag. Whereas decreases in activation delay caused by delayed gastrocnemius deactivation promote foot drag, all other changes associated with iSCI facilitate foot swing. Our results suggest that even small changes in the ability to precisely deactivate the gastrocnemius could result in foot drag after iSCI. Copyright © 2015 the American Physiological Society.

  13. Inhibitory effects of devil's claw (secondary root of Harpagophytum procumbens) extract and harpagoside on cytokine production in mouse macrophages.

    Science.gov (United States)

    Inaba, Kazunori; Murata, Kazuya; Naruto, Shunsuke; Matsuda, Hideaki

    2010-04-01

    Successive oral administration (50 mg/kg) of a 50% ethanolic extract (HP-ext) of devil's claw, the secondary root of Harpagophytum procumbens, showed a significant anti-inflammatory effect in the rat adjuvant-induced chronic arthritis model. HP-ext dose-dependently suppressed the lipopolysaccharide (LPS)-induced production of inflammatory cytokines [interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha)] in mouse macrophage cells (RAW 264.7). Harpagoside, a major iridoid glycoside present in devil's claw, was found to be one of the active agents in HP-ext and inhibited the production of IL-1beta, IL-6, and TNF-alpha by RAW 264.7.

  14. Impact of oxidative stress on exercising skeletal muscle.

    Science.gov (United States)

    Steinbacher, Peter; Eckl, Peter

    2015-04-10

    It is well established that muscle contractions during exercise lead to elevated levels of reactive oxygen species (ROS) in skeletal muscle. These highly reactive molecules have many deleterious effects, such as a reduction of force generation and increased muscle atrophy. Since the discovery of exercise-induced oxidative stress several decades ago, evidence has accumulated that ROS produced during exercise also have positive effects by influencing cellular processes that lead to increased expression of antioxidants. These molecules are particularly elevated in regularly exercising muscle to prevent the negative effects of ROS by neutralizing the free radicals. In addition, ROS also seem to be involved in the exercise-induced adaptation of the muscle phenotype. This review provides an overview of the evidences to date on the effects of ROS in exercising muscle. These aspects include the sources of ROS, their positive and negative cellular effects, the role of antioxidants, and the present evidence on ROS-dependent adaptations of muscle cells in response to physical exercise.

  15. Voltage directive drive with claw pole motor and control without rotor position indicator

    Science.gov (United States)

    Stroenisch, Volker Ewald

    Design and testing of a voltage directive drive for synchronous variable speed claw pole motor and control without rotor position indicator is described. Economic analysis of the designed regulation is performed. Computations of stationary and dynamic behavior are given and experimental operational behavior is determined. The motors can be used for electric transportation vehicles, diesel motors, and electric railway engines.

  16. Usefulness of muscle denervation as an MRI sign of peripheral nerve pathology

    International Nuclear Information System (INIS)

    Lisle, D. A.; Johnstone, S. A.

    2007-01-01

    Full text: Peripheral nerve disorders may be classified into compressive or entrapment neuropathies and non-compressive neuropathies. Muscle denervation recognized on MRI may be a useful sign in the diagnosis of peripheral nerve disorders. Acute or subacute denervation results in prolonged T 2 relaxation time, producing increased signal in skeletal muscle on short tau inversion-recovery and fat-suppressed T 2 -weighted images. Chronic denervation produces fatty atrophy of skeletal muscles, resulting in increased muscle signal on T 1 -weighted images. This review will outline and illustrate the various ways that muscle denervation as seen on MRI may assist in the diagnosis and localization of peripheral nerve disorders

  17. Interventions Targeting Glucocorticoid-Krüppel-like Factor 15-Branched-Chain Amino Acid Signaling Improve Disease Phenotypes in Spinal Muscular Atrophy Mice

    Directory of Open Access Journals (Sweden)

    Lisa M. Walter

    2018-05-01

    Full Text Available The circadian glucocorticoid-Krüppel-like factor 15-branched-chain amino acid (GC-KLF15-BCAA signaling pathway is a key regulatory axis in muscle, whose imbalance has wide-reaching effects on metabolic homeostasis. Spinal muscular atrophy (SMA is a neuromuscular disorder also characterized by intrinsic muscle pathologies, metabolic abnormalities and disrupted sleep patterns, which can influence or be influenced by circadian regulatory networks that control behavioral and metabolic rhythms. We therefore set out to investigate the contribution of the GC-KLF15-BCAA pathway in SMA pathophysiology of Taiwanese Smn−/−;SMN2 and Smn2B/− mouse models. We thus uncover substantial dysregulation of GC-KLF15-BCAA diurnal rhythmicity in serum, skeletal muscle and metabolic tissues of SMA mice. Importantly, modulating the components of the GC-KLF15-BCAA pathway via pharmacological (prednisolone, genetic (muscle-specific Klf15 overexpression and dietary (BCAA supplementation interventions significantly improves disease phenotypes in SMA mice. Our study highlights the GC-KLF15-BCAA pathway as a contributor to SMA pathogenesis and provides several treatment avenues to alleviate peripheral manifestations of the disease. The therapeutic potential of targeting metabolic perturbations by diet and commercially available drugs could have a broader implementation across other neuromuscular and metabolic disorders characterized by altered GC-KLF15-BCAA signaling. Keywords: Spinal muscular atrophy, KLF15, Glucocorticoids, Branched-chain amino acids, Metabolism, Therapy

  18. Bion 11 Spaceflight Project: Effect of Weightlessness on Single Muscle Fiber Function in Rhesus Monkeys

    Science.gov (United States)

    Fitts, Robert H.; Romatowski, Janell G.; Widrick, Jeffrey J.; DeLaCruz, Lourdes

    1999-01-01

    Although it is well known that microgravity induces considerable limb muscle atrophy, little is known about how weightlessness alters cell function. In this study, we investigated how weightlessness altered the functional properties of single fast and slow striated muscle fibers. Physiological studies were carried out to test the hypothesis that microgravity causes fiber atrophy, a decreased peak force (Newtons), tension (Newtons/cross-sectional area) and power, an elevated peak rate of tension development (dp/dt), and an increased maximal shortening velocity (V(sub o)) in the slow type I fiber, while changes in the fast-twitch fiber are restricted to atrophy and a reduced peak force. For each fiber, we determined the peak force (P(sub o)), V(sub o), dp/dt, the force-velocity relationship, peak power, the power-force relationship, the force-pCa relationship, and fiber stiffness. Biochemical studies were carried out to assess the effects of weightlessness on the enzyme and substrate profile of the fast- and slow-twitch fibers. We predicted that microgravity would increase resting muscle glycogen and glycolytic metabolism in the slow fiber type, while the fast-twitch fiber enzyme profile would be unaltered. The increased muscle glycogen would in part result from an elevated hexokinase and glycogen synthase. The enzymes selected for study represent markers for mitochondrial function (citrate synthase and 0-hydroxyacyl-CoA dehydrogenase), glycolysis (Phosphofructokinase and lactate dehydrogenase), and fatty acid transport (Carnitine acetyl transferase). The substrates analyzed will include glycogen, lactate, adenosine triphosphate, and phosphocreatine.

  19. Acupuncture plus Low-Frequency Electrical Stimulation (Acu-LFES Attenuates Diabetic Myopathy by Enhancing Muscle Regeneration.

    Directory of Open Access Journals (Sweden)

    Zhen Su

    Full Text Available Mortality and morbidity are increased in patients with muscle atrophy resulting from catabolic diseases such as diabetes. At present there is no pharmacological treatment that successfully reverses muscle wasting from catabolic conditions. We hypothesized that acupuncture plus low frequency electric stimulation (Acu-LFES would mimic the impact of exercise and prevent diabetes-induced muscle loss. Streptozotocin (STZ was used to induce diabetes in mice. The mice were then treated with Acu-LFES for 15 minutes daily for 14 days. Acupuncture points were selected according to the WHO Standard Acupuncture Nomenclature guide. The needles were connected to an SDZ-II electronic acupuncture device delivering pulses at 20Hz and 1mA. Acu-LFES prevented soleus and EDL muscle weight loss and increased hind-limb muscle grip function in diabetic mice. Muscle regeneration capacity was significantly increased by Acu-LFES. The expression of Pax7, MyoD, myogenin and embryo myosin heavy chain (eMyHC was significantly decreased in diabetic muscle vs. control muscle. The suppressed levels in diabetic muscle were reversed by Acu-LFES. The IGF-1 signaling pathway was also upregulated by Acu-LFES. Phosphorylation of Akt, mTOR and p70S6K were downregulated by diabetes leading to a decline in muscle mass, however, Acu-LFES countered the diabetes-induced decline. In addition, microRNA-1 and -206 were increased by Acu-LFES after 24 days of treatment. We conclude that Acu-LFES is effective in counteracting diabetes-induced skeletal muscle atrophy by increasing IGF-1 and its stimulation of muscle regeneration.

  20. Design and Implementation of a Brain Computer Interface System for Controlling a Robotic Claw

    Science.gov (United States)

    Angelakis, D.; Zoumis, S.; Asvestas, P.

    2017-11-01

    The aim of this paper is to present the design and implementation of a brain-computer interface (BCI) system that can control a robotic claw. The system is based on the Emotiv Epoc headset, which provides the capability of simultaneous recording of 14 EEG channels, as well as wireless connectivity by means of the Bluetooth protocol. The system is initially trained to decode what user thinks to properly formatted data. The headset communicates with a personal computer, which runs a dedicated software application, implemented under the Processing integrated development environment. The application acquires the data from the headset and invokes suitable commands to an Arduino Uno board. The board decodes the received commands and produces corresponding signals to a servo motor that controls the position of the robotic claw. The system was tested successfully on a healthy, male subject, aged 28 years. The results are promising, taking into account that no specialized hardware was used. However, tests on a larger number of users is necessary in order to draw solid conclusions regarding the performance of the proposed system.