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Sample records for prevent muscle atrophy

  1. 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

  2. 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.

  3. 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.

  4. Muscle atrophy

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    ... 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 ...

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

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    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.

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

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    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

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

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    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.

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

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    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.

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

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    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.

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

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    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.

  11. 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.

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

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    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.

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

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    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.

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

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    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

  15. Electrical stimulation attenuates morphological alterations and prevents atrophy of the denervated cranial tibial muscle.

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    Bueno, Cleuber Rodrigo de Souza; Pereira, Mizael; Favaretto, Idvaldo Aparecido; Bortoluci, Carlos Henrique Fachin; Santos, Thais Caroline Pereira Dos; Dias, Daniel Ventura; Daré, Letícia Rossi; Rosa, Geraldo Marco

    2017-01-01

    To investigate if electrical stimulation through Russian current is able to maintain morphology of the cranial tibial muscle of experimentally denervated rats. Thirty-six Wistar rats were divided into four groups: the Initial Control Group, Final Control Group, Experimental Denervated and Treated Group, Experimental Denervated Group. The electrostimulation was performed with a protocol of Russian current applied three times per week, for 45 days. At the end, the animals were euthanized and histological and morphometric analyses were performed. Data were submitted to statistical analysis with a significance level of pprotocolo de corrente russa aplicada três vezes por semanas, durante 45 dias. Ao final, os animais foram eutanasiados e, em seguida, foram realizadas as análises histológica e morfométrica. Os dados foram submetidos à análise estatística, com nível de significância de p<0,05. Os Grupos Experimental Desnervado e o Grupo Experimental Desnervado Tratado apresentaram área de secção transversal da fibra menor quando comparados ao Grupo Controle Final. Entretanto, constatou-se diferença significativa entre o Grupo Experimental Desnervado e o Grupo Experimental Desnervado Tratado, mostrando que a estimulação elétrica minimizou atrofia muscular. Ainda, observou-se que o Grupo Experimental Desnervado Tratado apresentou resultados semelhantes ao Grupo Controle Inicial. A estimulação elétrica por meio da corrente russa foi favorável na manutenção da morfologia do músculo tibial cranial desnervado experimentalmente, minimizando a atrofia muscular.

  16. 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

  17. 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.

  18. 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.

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    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.

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

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    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

  20. 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

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

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    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

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

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    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.

  3. 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

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

    Science.gov (United States)

    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.

  5. 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

  6. 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.

  7. 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 ...

  8. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  10. 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

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

    Science.gov (United States)

    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.

  12. 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.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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

  16. 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.

  17. 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

  18. 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...

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

    Science.gov (United States)

    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

  20. 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.

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

    Directory of Open Access Journals (Sweden)

    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. 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...

  3. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  5. 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.

  6. 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.

  7. 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

  8. 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.

  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. 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.

  11. 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

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

    Science.gov (United States)

    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.

  13. 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...

  14. 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.

  15. 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.

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

    Science.gov (United States)

    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

  17. 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

  18. 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

  19. 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...

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

    Science.gov (United States)

    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.

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  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. 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)

  10. 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

  11. 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

  12. 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.

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

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    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. 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.

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

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

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    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. 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.)

  18. Atrophy rates in asymptomatic amyloidosis: implications for Alzheimer prevention trials.

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    K Abigail Andrews

    Full Text Available There is considerable interest in designing therapeutic studies of individuals at risk of Alzheimer disease (AD to prevent the onset of symptoms. Cortical β-amyloid plaques, the first stage of AD pathology, can be detected in vivo using positron emission tomography (PET, and several studies have shown that ~1/3 of healthy elderly have significant β-amyloid deposition. Here we assessed whether asymptomatic amyloid-PET-positive controls have increased rates of brain atrophy, which could be harnessed as an outcome measure for AD prevention trials. We assessed 66 control subjects (age = 73.5±7.3 yrs; MMSE = 29±1.3 from the Australian Imaging Biomarkers & Lifestyle study who had a baseline Pittsburgh Compound B (PiB PET scan and two 3T MRI scans ~18-months apart. We calculated PET standard uptake value ratios (SUVR, and classified individuals as amyloid-positive/negative. Baseline and 18-month MRI scans were registered, and brain, hippocampal, and ventricular volumes and annualized volume changes calculated. Increasing baseline PiB-PET measures of β-amyloid load correlated with hippocampal atrophy rate independent of age (p = 0.014. Twenty-two (1/3 were PiB-positive (SUVR>1.40, the remaining 44 PiB-negative (SUVR≤1.31. Compared to PiB-negatives, PiB-positive individuals were older (76.8±7.5 vs. 71.7±7.5, p<0.05 and more were APOE4 positive (63.6% vs. 19.2%, p<0.01 but there were no differences in baseline brain, ventricle or hippocampal volumes, either with or without correction for total intracranial volume, once age and gender were accounted for. The PiB-positive group had greater total hippocampal loss (0.06±0.08 vs. 0.02±0.05 ml/yr, p = 0.02, independent of age and gender, with non-significantly higher rates of whole brain (7.1±9.4 vs. 4.7±5.5 ml/yr and ventricular (2.0±3.0 vs. 1.1±1.0 ml/yr change. Based on the observed effect size, recruiting 384 (95%CI 195-1080 amyloid-positive subjects/arm will provide 80% power to detect 25

  19. 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

  20. 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.

  1. 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;

  2. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  5. 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

  6. 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.

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

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    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.

  8. 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.

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

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    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.

  10. 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...

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

    Energy Technology Data Exchange (ETDEWEB)

    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.)

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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.

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

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    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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  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. 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.)

  8. 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.)

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  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. 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.

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. 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

  8. 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.

  9. 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.)

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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

  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. 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

  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. 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.

  20. 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.

  1. 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.)

  2. 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...

  3. 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...

  4. 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.

  5. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  7. 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...

  8. 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.

  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. 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.

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. 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)

  16. 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

  17. 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.

  18. 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.

  19. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  1. 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....

  2. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  4. 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...

  5. 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)/...

  6. 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

  7. 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.

  8. [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.

  9. 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

  10. 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.

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

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    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

  12. 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

  13. 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.

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

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    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.

  15. 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.

  16. 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.

  17. 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

  18. 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

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

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    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.

  20. 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.

  1. 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.

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

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    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

  3. 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.

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

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    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.

  5. Albumin infusion after reperfusion prevents gut ischemia-reperfusion-induced gut-associated lymphoid tissue atrophy.

    Science.gov (United States)

    Ikezawa, Fumie; Fukatsu, Kazuhiko; Moriya, Tomoyuki; Maeshima, Yoshinori; Okamoto, Koichi; Hara, Etsuko; Hiraide, Hoshio; Compher, Charlene W

    2006-01-01

    Our recent study clarified that gut ischemia-reperfusion (I/R) causes gut-associated lymphoid tissue (GALT) mass atrophy, a possible mechanism for increased morbidity of infectious complications after severe surgical insults. Because albumin administration reportedly reduces hemorrhagic shock-induced lung injury, we hypothesized that albumin treatment prevents GALT atrophy due to gut I/R. Male mice (n = 37) were randomized to albumin, normal saline, and sham groups. All groups underwent jugular vein catheter insertion. The albumin and normal saline groups underwent 75-minute occlusion of the superior mesenteric artery. During gut ischemia, all mice received normal saline infusions at 1.0 mL/h. The albumin group was given 5% bovine serum albumin in normal saline at 1.0 mL/h for 60 minutes after reperfusion, whereas the normal saline group received 0.9% sodium chloride at 1.0 mL/h. The sham group underwent laparotomy only. Mice were killed on day 1 or 7, and the entire small intestine was harvested. GALT lymphocytes were isolated and counted. Their phenotypes (alphabetaTCR, gammadeltaTCR, CD4, CD8, B220) were determined by flow cytometry. On day 1, the gut I/R groups showed significantly lower total lymphocyte and B cell numbers in Peyer's patches and the lamina propria than the sham group. However, the albumin infusion partially but significantly restored these cell numbers. On day 7, there were no significant differences in any of the parameters measured among the 3 groups. Albumin infusion after a gut ischemic insult may maintain gut immunity by preventing GALT atrophy.

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

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    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.

  7. 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.

  8. 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.

  9. Glutamate prevents intestinal atrophy via luminal nutrient sensing in a mouse model of total parenteral nutrition

    DEFF Research Database (Denmark)

    Xiao, Weidong; Feng, Yongjia; Holst, Jens Juul

    2014-01-01

    significantly changed the amount of T1Rs, GLM receptors, and transporters, and GLM prevented these changes. GLM significantly prevented TPN-associated intestinal atrophy (2.5-fold increase in IEC proliferation) and was dependent on up-regulation of the protein kinase pAkt, but independent of T1R3 and mGluR5...... signaling. GLM led to a loss of EBF with TPN (60% increase in FITC-dextran permeability, 40% decline in transepithelial resistance); via T1R3, it protected EBF, whereas mGluR5 was associated with EBF loss. GLM led to a decline in circulating glucagon-like peptide 2 (GLP-2) during TPN. The decline...

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

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    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

  11. 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.

  12. 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

  13. 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

  14. 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.

  15. 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.

  16. Increased autophagy and apoptosis contribute to muscle atrophy in a myotonic dystrophy type 1 Drosophila model

    Directory of Open Access Journals (Sweden)

    Ariadna Bargiela

    2015-07-01

    Full Text Available Muscle mass wasting is one of the most debilitating symptoms of myotonic dystrophy type 1 (DM1 disease, ultimately leading to immobility, respiratory defects, dysarthria, dysphagia and death in advanced stages of the disease. In order to study the molecular mechanisms leading to the degenerative loss of adult muscle tissue in DM1, we generated an inducible Drosophila model of expanded CTG trinucleotide repeat toxicity that resembles an adult-onset form of the disease. Heat-shock induced expression of 480 CUG repeats in adult flies resulted in a reduction in the area of the indirect flight muscles. In these model flies, reduction of muscle area was concomitant with increased apoptosis and autophagy. Inhibition of apoptosis or autophagy mediated by the overexpression of DIAP1, mTOR (also known as Tor or muscleblind, or by RNA interference (RNAi-mediated silencing of autophagy regulatory genes, achieved a rescue of the muscle-loss phenotype. In fact, mTOR overexpression rescued muscle size to a size comparable to that in control flies. These results were validated in skeletal muscle biopsies from DM1 patients in which we found downregulated autophagy and apoptosis repressor genes, and also in DM1 myoblasts where we found increased autophagy. These findings provide new insights into the signaling pathways involved in DM1 disease pathogenesis.

  17. Prevention of pectus excavatum for children with spinal muscular atrophy type 1.

    Science.gov (United States)

    Bach, John R; Bianchi, Carlo

    2003-10-01

    To demonstrate the elimination of pectus excavatum and promotion of more normal lung growth and chest wall development by the use of high-span positive inspiratory pressure plus positive end-expiratory pressure (PIP+PEEP), patients with spinal muscular atrophy type 1 with paradoxical breathing were placed on high-span PIP+PEEP when sleeping from the point of diagnosis of spinal muscular atrophy. Although the appearance of pectus excavatum is ubiquitous in untreated infants with spinal muscular atrophy type 1, after institution of high-span PIP+PEEP, pectus resolves and lungs and chest walls grow more normally. High-span PIP+PEEP is indicated for all infants diagnosed with spinal muscular atrophy who demonstrate paradoxical breathing for the purpose of promoting more normal lung and chest development.

  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.

    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

  19. Acute resistance exercise reduces increased gene expression in muscle atrophy of ovariectomised arthritic rats

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    Roberto Furlanetto Jr

    2017-02-01

    Full Text Available Objective: We studied the effect of resistance exercise (RE on mRNA levels of atrogin-1, MuRF-1, and myostatin in the gastrocnemius muscle of arthritic rats after loss of ovarian function (LOF. Material and methods : Thirty female Wistar rats (nine weeks old, 195.3 ±17.4 grams were randomly allocated into five groups: control group (CT-Sham; n = 6; group with rheumatoid arthritis (RA; n = 6; group with rheumatoid arthritis subjected to RE (RAEX; n = 6; ovariectomy group with rheumatoid arthritis (RAOV; n = 6; and an ovariectomy group with rheumatoid arthritis subjected to RE (RAOVEX; n = 6. After 15 days of intra-articular injections with Met-BSA the animals were subjected to RE and six hours after workout were euthanised. Results : The rheumatoid arthritis provoked reduction in the cross-sectional area (CSA of muscle fibres, but the CSA was lower in the RAOV when compared to the RA groups. Skeletal muscle atrogin-1 mRNA level was increased in arthritic rats (RA and RAOV, but the atrogin-1 level was higher in RAOV group when compared to other arthritic groups. The Muscle MuRF-1 mRNA level was also increased in the RAOV group. The increased atrogin-1 and MuRF-1 mRNA levels were lower in the RAOVEX group than in the RAOV group. The myostatin mRNA level was similar in all groups, except for the RAOVEX group, in which it was lower than the other groups. Conclusions : LOF results in increased loss of skeletal muscle-related ubiquitin ligases (atrogin-1 and MuRF-1. However, the RE reduces the atrogin-1, MuRF-1, and myostatin mRNA levels in muscle of arthritic rats affected by LOF.

  20. Constant Fiber Number During Skeletal Muscle Atrophy and Modified Arachidonate Metabolism During Hypertrophy

    Science.gov (United States)

    Templeton, G.

    1985-01-01

    A previously documented shift from Type I to IIA predominance of the soleus muscle during rat suspension was further investigated to determine if this shift was by selective reduction of a single fiber type, simultaneous reduction and formation of fibers with different fiber types, or a transformation of fiber type by individual fibers. By partial acid digestion and dissection, average total soleus fiber number was found to be 3022 + or - 80 (SE) and 3008 + or - 64 before and after four-week suspension (n=12). Another area of current research was based on previous studies which indicate that prostaglandins are biosynthesized by skeletal muscle and evoke protein synthesis and degradation.

  1. Muscle wasting and impaired myogenesis in tumor bearing mice are prevented by ERK inhibition.

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    Fabio Penna

    Full Text Available BACKGROUND: The onset of cachexia is a frequent feature in cancer patients. Prominent characteristic of this syndrome is the loss of body and muscle weight, this latter being mainly supported by increased protein breakdown rates. While the signaling pathways dependent on IGF-1 or myostatin were causally involved in muscle atrophy, the role of the Mitogen-Activated-Protein-Kinases is still largely debated. The present study investigated this point on mice bearing the C26 colon adenocarcinoma. METHODOLOGY/PRINCIPAL FINDINGS: C26-bearing mice display a marked loss of body weight and muscle mass, this latter associated with increased phosphorylated (p-ERK. Administration of the ERK inhibitor PD98059 to tumor bearers attenuates muscle depletion and weakness, while restoring normal atrogin-1 expression. In C26 hosts, muscle wasting is also associated with increased Pax7 expression and reduced myogenin levels. Such pattern, suggestive of impaired myogenesis, is reversed by PD98059. Increased p-ERK and reduced myosin heavy chain content can be observed in TNFα-treated C2C12 myotubes, while decreased myogenin and MyoD levels occur in differentiating myoblasts exposed to the cytokine. All these changes are prevented by PD98059. CONCLUSIONS/SIGNIFICANCE: These results demonstrate that ERK is involved in the pathogenesis of muscle wasting in cancer cachexia and could thus be proposed as a therapeutic target.

  2. 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.

  3. FHL1 activates myostatin signalling in skeletal muscle and promotes atrophy

    OpenAIRE

    Kemp, P; Lee, JY; lori, O; Wells, D

    2015-01-01

    Myostatin is a TGFβ family ligand that reduces muscle mass. In cancer cells, TGFβ signalling is increased by the protein FHL1. Consequently, FHL1 may promote signalling by myostatin. We therefore tested the ability of FHL1 to regulate myostatin function. FHL1 increased the myostatin activity on a SMAD reporter and increased myostatin dependent myotube wasting. In mice, independent expression of myostatin reduced fibre diameter whereas FHL1 increased fibre diameter, both consistent with previo...

  4. 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.

  5. 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 ...

  6. Leucine minimizes denervation-induced skeletal muscle atrophy of rats through akt/mtor signaling pathways

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    Carolina Barbosa Ribeiro

    2015-03-01

    Full Text Available The aim of the present study was to evaluate the effect of leucine treatment (0.30 mM on muscle weight and signaling of myoproteins related to synthesis and degradation pathways of soleus muscle following seven days of complete sciatic nerve lesion.Wistar rats (n=24 of 3 to 4 months of age (192 ± 23 g were used. The animals were randomly distributed into four experimental groups (n=6/group: control, treated with leucine (L, denervated (D and denervated treated with leucine (DL.Dependent measures were proteins levels of AKT, AMPK, mTOR, and ACC performed by Western blot. Leucine induced a reduction in the phosphorylation of AMPK (p<0.05 by 16% in the L and by 68% in the DL groups as compared with control group. Denervation increased AMPK by 24% in the D group as compared with the control group (p<0.05. AKT was also modulated by denervation and leucine treatment, highlighted by the elevation of AKT phosphorylation in the D (65%, L (98% and DL (146% groups as compared with the control group (p<0.05. AKT phosphorylation was 49% higher in the D group as compared with the DL group.Furthermore, denervation decreased mTOR phosphorylation by 29% in the D group as compared with the control group. However, leucine treatment induced an increase of 49% in the phosphorylation of mTOR in the L group as compared with the control group, and an increase of 154% in the DL as compared with the D group ( p<0.05. ACC phosphorylation was 20% greater in the D group than the control group. Furthermore, ACC in the soleus was 22% lower in the in the L group and 50% lower in the DL group than the respective control group (p<0.05.In conclusion, leucine treatment minimized the deleterious effects of denervation on rat soleus muscle by increasing anabolic (AKT and mTOR and decreasing catabolic (AMPK pathways. These results may be interesting for muscle recovery following acute denervation, which may contribute to musculoskeletal rehabilitation after denervation.

  7. 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

  8. 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

  9. Mesenchymal Stem Cell Secretome: A Potential Tool for the Prevention of Muscle Degenerative Changes Associated With Chronic Rotator Cuff Tears.

    Science.gov (United States)

    Sevivas, Nuno; Teixeira, Fábio Gabriel; Portugal, Raquel; Araújo, Luís; Carriço, Luís Filipe; Ferreira, Nuno; Vieira da Silva, Manuel; Espregueira-Mendes, João; Anjo, Sandra; Manadas, Bruno; Sousa, Nuno; Salgado, António J

    2016-08-08

    Massive rotator cuff tears (MRCTs) are usually chronic lesions with pronounced degenerative changes, where advanced fatty degeneration and atrophy can make the tear irreparable. Human mesenchymal stem cells (hMSCs) secrete a range of growth factors and vesicular systems, known as secretome, that mediates regenerative processes in tissues undergoing degeneration. To study the effect of hMSC secretome on muscular degenerative changes and shoulder function on a rat MRCT model. Controlled laboratory study. A bilateral 2-tendon (supraspinatus and infraspinatus) section was performed to create an MRCT in a rat model. Forty-four Wistar-Han rats were randomly assigned to 6 groups: control group (sham surgery), lesion control group (MRCT), and 4 treated-lesion groups according to the site and periodicity of hMSC secretome injection: single local injection, multiple local injections, single systemic injection, and multiple systemic injections. Forelimb function was analyzed with the staircase test. Atrophy and fatty degeneration of the muscle were evaluated at 8 and 16 weeks after injury. A proteomic analysis was conducted to identify the molecules present in the hMSC secretome that can be associated with muscular degeneration prevention. When untreated for 8 weeks, the MRCT rats exhibited a significantly higher fat content (0.73% ± 0.19%) compared with rats treated with a single local injection (0.21% ± 0.04%; P muscle atrophy, 8 weeks after injury, only the single local injection group (0.0993% ± 0.0036%) presented a significantly higher muscle mass than that of the untreated MRCT group (0.0794% ± 0.0047%; P muscle regeneration, namely, pigment epithelium-derived factor and follistatin. The study data suggest that hMSC secretome effectively decreases the fatty degeneration and atrophy of the rotator cuff muscles. We describe a new approach for decreasing the characteristic muscle degeneration associated with chronic rotator cuff tears. This strategy is particularly

  10. [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.

  11. Whey Proteins Are More Efficient than Casein in the Recovery of Muscle Functional Properties following a Casting Induced Muscle Atrophy

    Science.gov (United States)

    Martin, Vincent; Ratel, Sébastien; Siracusa, Julien; Le Ruyet, Pascale; Savary-Auzeloux, Isabelle; Combaret, Lydie; Guillet, Christelle; Dardevet, Dominique

    2013-01-01

    The purpose of this study was to investigate the effect of whey supplementation, as compared to the standard casein diet, on the recovery of muscle functional properties after a casting-induced immobilization period. After an initial (I0) evaluation of the contractile properties of the plantarflexors (isometric torque-frequency relationship, concentric power-velocity relationship and a fatigability test), the ankle of 20 male adult rats was immobilized by casting for 8 days. During this period, rats were fed a standard diet with 13% of casein (CAS). After cast removal, rats received either the same diet or a diet with 13% of whey proteins (WHEY). A control group (n = 10), non-immobilized but pair-fed to the two other experimental groups, was also studied and fed with the CAS diet. During the recovery period, contractile properties were evaluated 7 (R7), 21 (R21) and 42 days (R42) after cast removal. The immobilization procedure induced a homogeneous depression of average isometric force at R7 (CAS: − 19.0±8.2%; WHEY: − 21.7±8.4%; P<0.001) and concentric power (CAS: − 26.8±16.4%, P<0.001; WHEY: − 13.5±21.8%, P<0.05) as compared to I0. Conversely, no significant alteration of fatigability was observed. At R21, isometric force had fully recovered in WHEY, especially for frequencies above 50 Hz, whereas it was still significantly depressed in CAS, where complete recovery occurred only at R42. Similarly, recovery of concentric power was faster at R21 in the 500−700°/s range in the WHEY group. These results suggest that recovery kinetics varied between diets, the diet with the whey proteins promoting a faster recovery of isometric force and concentric power output as compared to the casein diet. These effects were more specifically observed at force level and movement velocities that are relevant for functional abilities, and thus natural locomotion. PMID:24069411

  12. A Ground-Based Comparison of the Muscle Atrophy Research and Exercise System (MARES) and a Standard Isokinetic Dynamometer

    Science.gov (United States)

    Hackney, K. J.; English, K. L.; Redd, E.; DeWitt, J. K.; Ploutz-Snyder, R.; Ploutz-Snyder, L. L.

    2010-01-01

    PURPOSE: 1) To compare the test-to-test reliability of Muscle Atrophy Research and Exercise System (MARES) with a standard laboratory isokinetic dynamometer (ISOK DYN) and; 2) to determine if measures of peak torque and total work differ between devices. METHODS: Ten subjects (6M, 4F) completed two trials on both MARES and an ISOK DYN in a counterbalanced order. Peak torque values at 60 deg & 180 deg / s were obtained from five maximal repetitions of knee extension (KE) and knee flexion (KF). Total work at 180 deg / s was determined from the area under the torque vs. displacement curve during twenty maximal repetitions of KE and KF. Reliability of measures within devices was interpreted from the intraclass correlation coefficient (ICC) and compared between devices using the ratio of the within-device standard deviations. Indicators of agreement for the two devices were evaluated from: 1) a calculation of concordance (rho) and; 2) the correlation between the mean of measures versus the delta difference between measures (m u vs delta). RESULTS: For all outcome measures ICCs were high for both the ISOK DYN (0.95-0.99) and MARES (0.90-0.99). However, ratios of the within-device standard deviation were 1.3 to 4.3 times higher on MARES. On average, a wide range (3.3 to 1054 Nm) of differences existed between the values obtained. Only KE peak torque measured at 60 deg & 180 deg / s showed similarities between devices (rho = 0.91 & 0.87; Pearson's r for m u vs delta = -0.22 & -0.37, respectively). CONCLUSION: Although MARES was designed for use in microgravity it was quite reliable during ground-based testing. However, MARES was consistently more variable than an ISOK DYN. Future longitudinal studies evaluating a change in isokinetic peak torque or total work should be limited within one device.

  13. 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.

  14. 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.

  15. 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.

  16. 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 ...

  17. 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

  18. 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.

  19. 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 ...

  20. 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.

  1. 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...

  2. L-leucine, beta-hydroxy-beta-methylbutyric acid (HMB) and creatine monohydrate prevent myostatin-induced Akirin-1/Mighty mRNA down-regulation and myotube atrophy.

    Science.gov (United States)

    Mobley, Christopher Brooks; Fox, Carlton D; Ferguson, Brian S; Amin, Rajesh H; Dalbo, Vincent J; Baier, Shawn; Rathmacher, John A; Wilson, Jacob M; Roberts, Michael D

    2014-01-01

    The purpose of this study was to examine if L-leucine (Leu), β-hydroxy-β-methylbutyrate (HMB), or creatine monohydrate (Crea) prevented potential atrophic effects of myostatin (MSTN) on differentiated C2C12 myotubes. After four days of differentiation, myotubes were treated with MSTN (10 ng/ml) for two additional days and four treatment groups were studied: 1) 3x per day 10 mM Leu, 2) 3x per day 10 mM HMB, 3) 3x per day 10 mM Crea, 4) DM only. Myotubes treated with DM without MSTN were analyzed as the control condition (DM/CTL). Following treatment, cells were analyzed for total protein, DNA content, RNA content, muscle protein synthesis (MPS, SUnSET method), and fiber diameter. Separate batch treatments were analyzed for mRNA expression patterns of myostatin-related genes (Akirin-1/Mighty, Notch-1, Ski, MyoD) as well as atrogenes (MuRF-1, and MAFbx/Atrogin-1). MSTN decreased fiber diameter approximately 30% compared to DM/CTL myotubes (p HMB and Crea prevented MSTN-induced atrophy. MSTN did not decrease MPS levels compared to DM/CTL myotubes, but MSTN treatment decreased the mRNA expression of Akirin-1/Mighty by 27% (p HMB myotubes had similar Akirin-1/Mighty and MyoD mRNA levels compared to DM/CTL myotubes. Furthermore, MSTN + Crea myotubes exhibited a 36% (p HMB and Crea may reduce MSTN-induced muscle fiber atrophy by influencing Akirin-1/Mighty mRNA expression patterns. Future studies are needed to examine if Leu, HMB and Crea independently or synergistically affect Akirin-1/Mighty expression, and how Akirin-1/Mighty expression mechanistically relates to skeletal muscle hypertrophy in vivo.

  3. Evaluation of atrophy of foot muscles in diabetic neuropathy -- a comparative study of nerve conduction studies and ultrasonography

    DEFF Research Database (Denmark)

    Severinsen, Kaare; Andersen, Henning

    2007-01-01

    OBJECTIVE: To evaluate the relation between the findings at nerve conduction studies and the size of small foot muscles determined by ultrasonography. METHODS: In 26 diabetic patients the size of the extensor digitorum brevis muscle (EDB) and of the muscles between the first and second metatarsal...... related to the size of the small foot muscles as determined by ultrasonography. SIGNIFICANCE: In diabetic patients motor nerve conduction studies can reliably determine the size of small foot muscles. Udgivelsesdato: 2007-Oct....... RESULTS: Seventeen patients fulfilled the criteria for diabetic neuropathy. The cross-sectional area of the EDB muscle and the thickness of the MIL muscle were 116 +/- 65 mm2 and 29.6 +/- 8.2 mm, respectively. Close relations were established between muscle size and the amplitude of the CMAP...

  4. 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.

  5. Diaphragm Muscle Weakness Following Acute Sustained Hypoxic Stress in the Mouse Is Prevented by Pretreatment with N-Acetyl Cysteine

    Directory of Open Access Journals (Sweden)

    Andrew J. O’Leary

    2018-01-01

    Full Text Available Oxygen deficit (hypoxia is a major feature of cardiorespiratory diseases characterized by diaphragm dysfunction, yet the putative role of hypoxic stress as a driver of diaphragm dysfunction is understudied. We explored the cellular and functional consequences of sustained hypoxic stress in a mouse model. Adult male mice were exposed to 8 hours of normoxia, or hypoxia (FiO2 = 0.10 with or without antioxidant pretreatment (N-acetyl cysteine, 200 mg/kg i.p.. Ventilation and metabolism were measured. Diaphragm muscle contractile function, myofibre size and distribution, gene expression, protein signalling cascades, and oxidative stress (TBARS were determined. Hypoxia caused pronounced diaphragm muscle weakness, unrelated to increased respiratory muscle work. Hypoxia increased diaphragm HIF-1α protein content and activated MAPK, mTOR, Akt, and FoxO3a signalling pathways, largely favouring protein synthesis. Hypoxia increased diaphragm lipid peroxidation, indicative of oxidative stress. FoxO3 and MuRF-1 gene expression were increased. Diaphragm 20S proteasome activity and muscle fibre size and distribution were unaffected by acute hypoxia. Pretreatment with N-acetyl cysteine substantially enhanced cell survival signalling, prevented hypoxia-induced diaphragm oxidative stress, and prevented hypoxia-induced diaphragm dysfunction. Hypoxia is a potent driver of diaphragm weakness, causing myofibre dysfunction without attendant atrophy. N-acetyl cysteine protects the hypoxic diaphragm and may have application as a potential adjunctive therapy.

  6. Role of the nervous system in sarcopenia and muscle atrophy with aging - strength training as a countermeasure

    DEFF Research Database (Denmark)

    Aagaard, Per; Suetta, Charlotte; Caserotti, Paolo

    2010-01-01

    and size (sarcopenia), resulting in impaired mechanical muscle performance that in turn leads to a reduced functional capacity during everyday tasks. Concurrently, maximum muscle strength, power, and rate of force development are decreased with aging, even in highly trained master athletes. The impairment...... to elicit effective countermeasures in elderly individuals even at a very old age (>80 years) by evoking muscle hypertrophy along with substantial changes in neuromuscular function, respectively. Notably, the training-induced changes in muscle mass and nervous system function leads to an improved functional...

  7. Development of a risk score for geographic atrophy in complications of the age-related macular degeneration prevention trial.

    Science.gov (United States)

    Ying, Gui-Shuang; Maguire, Maureen G

    2011-02-01

    To develop a risk score for developing geographic atrophy (GA) involving easily obtainable information among patients with bilateral large drusen. Cohort study within a multicenter randomized clinical trial. We included 1052 participants with ≥ 10 large (>125 μm) drusen and visual acuity ≥ 20/40 in each eye. In the Complications of Age-related Macular Degeneration (AMD) Prevention Trial (CAPT), 1 eye of each participant was randomly assigned to laser treatment and the contralateral eye was assigned to observation to evaluate whether laser treatment of drusen could prevent vision loss. Gradings by a reading center were used to identify: CAPT end point GA (total area of GA [>250 μm] > 1 disc area), GA (>175 μm) involving the foveal center (CGA), and GA of any size and location (any GA). Established risk factors (age, smoking status, hypertension, Age-related Eye Disease Study simple severity scale score), both with and without a novel risk factor (night vision score), were used in assigning risk points. The risk scores were evaluated for the ability to discriminate and calibrate GA risk. Development of end point GA, CGA, and any GA. Among 942 CAPT participants who completed 5 years of follow-up and did not have any GA at baseline, 6.8% participants developed CAPT end point GA, 9.6% developed CGA, and 34.4% developed any GA. The 5-year incidence of end point GA in 1 or both eyes of a participant increased with the 15-point GA risk score, from 0.6% for prevention of GA and for clinical assessment of GA risk in early AMD patients. Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

  8. 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.

  9. Role of the nervous system in sarcopenia and muscle atrophy with aging: strength training as a countermeasure

    DEFF Research Database (Denmark)

    Aagaard, P; Suetta, C; Caserotti, P

    2010-01-01

    and size (sarcopenia), resulting in impaired mechanical muscle performance that in turn leads to a reduced functional capacity during everyday tasks. Concurrently, maximum muscle strength, power, and rate of force development are decreased with aging, even in highly trained master athletes. The impairment...

  10. Satellite cell depletion prevents fiber hypertrophy in skeletal muscle.

    Science.gov (United States)

    Egner, Ingrid M; Bruusgaard, Jo C; Gundersen, Kristian

    2016-08-15

    The largest mammalian cells are the muscle fibers, and they have multiple nuclei to support their large cytoplasmic volumes. During hypertrophic growth, new myonuclei are recruited from satellite stem cells into the fiber syncytia, but it was recently suggested that such recruitment is not obligatory: overload hypertrophy after synergist ablation of the plantaris muscle appeared normal in transgenic mice in which most of the satellite cells were abolished. When we essentially repeated these experiments analyzing the muscles by immunohistochemistry and in vivo and ex vivo imaging, we found that overload hypertrophy was prevented in the satellite cell-deficient mice, in both the plantaris and the extensor digitorum longus muscles. We attribute the previous findings to a reliance on muscle mass as a proxy for fiber hypertrophy, and to the inclusion of a significant number of regenerating fibers in the analysis. We discuss that there is currently no model in which functional, sustainable hypertrophy has been unequivocally demonstrated in the absence of satellite cells; an exception is re-growth, which can occur using previously recruited myonuclei without addition of new myonuclei. © 2016. Published by The Company of Biologists Ltd.

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

    OpenAIRE

    Simona Boncompagni

    2012-01-01

    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...

  12. β-Hydroxy-β-methylbutyrate (HMB) enhances the proliferation of satellite cells in fast muscles of aged rats during recovery from disuse atrophy.

    Science.gov (United States)

    Alway, Stephen E; Pereira, Suzette L; Edens, Neile K; Hao, Yanlei; Bennett, Brian T

    2013-09-01

    Loss of myonuclei by apoptosis is thought to contribute to sarcopenia. We have previously shown, that the leucine metabolite, β-hydroxy-β-methylbutyrate (HMB) suppresses apoptotic signaling and the apoptotic index (the ratio of apoptotic positive to apoptotic negative myonuclei) during muscle disuse and during reloading periods after disuse in aged rats. However, it was not clear if the apoptotic signaling indexes were due only to preservation of myonuclei or if perhaps the total myogenic pool increased as a result of HMB-mediated satellite cell proliferation as this would have also reduced the apoptotic index. In this study, we tested the hypothesis that HMB would augment myogenic cells (satellite cells) proliferation during muscle recovery (growth) after a period of disuse in senescent animals. The hindlimb muscles of 34 month old Fisher 344 × Brown Norway rats were unloaded for 14 days by hindlimb suspension (HLS), and then reloaded for 14 days. The rats received either Ca-HMB (340 mg/kg body weight; n = 16), or the vehicle (n = 10) by gavage throughout the experimental period. HMB prevented the functional decline in maximal plantar flexion isometric force production during the reloading period, but not during HLS. HMB-treatment enhanced the proliferation of muscle stem cells as shown by a greater percentage of satellite cells that had proliferated (more BrdU positive, Pax-7 positive, and more Pax7/Ki67 positive nuclei) and as a result, more differentiated stem cells were present (more MyoD/myogenin positive myonuclei), relative to total myonuclei, in reloaded plantaris muscles as compared to reloaded muscles from vehicle-treated animals. Furthermore HMB increased the nuclear protein abundance of proliferation markers, inhibitor of differentiation-2 and cyclin A, as compared to vehicle treatment in reloaded muscles. Although HMB increased phosphorylated Akt during reloading, other mTOR related proteins were not altered by HMB treatment. These data show that

  13. Botulinum Toxin Type A Injections in the Psoas Muscle of Children with Cerebral Palsy: Muscle Atrophy after Motor End Plate-Targeted Injections

    Science.gov (United States)

    Van Campenhout, Anja; Verhaegen, Ann; Pans, Steven; Molenaers, Guy

    2013-01-01

    MEP targeting during BoNT-A injections has been demonstrated to improve outcome. Two injection techniques of the psoas muscle--proximal MEP targeting versus a widely used more distal injection technique--are compared using muscle volume assessment by digital MRI segmentation as outcome measure. Method: 7 spastic diplegic children received…

  14. Irisin is a pro-myogenic factor that induces skeletal muscle hypertrophy and rescues denervation-induced atrophy.

    Science.gov (United States)

    Reza, Musarrat Maisha; Subramaniyam, Nathiya; Sim, Chu Ming; Ge, Xiaojia; Sathiakumar, Durgalakshmi; McFarlane, Craig; Sharma, Mridula; Kambadur, Ravi

    2017-10-24

    Exercise induces expression of the myokine irisin, which is known to promote browning of white adipose tissue and has been shown to mediate beneficial effects following exercise. Here we show that irisin induces expression of a number of pro-myogenic and exercise response genes in myotubes. Irisin increases myogenic differentiation and myoblast fusion via activation of IL6 signaling. Injection of irisin in mice induces significant hypertrophy and enhances grip strength of uninjured muscle. Following skeletal muscle injury, irisin injection improves regeneration and induces hypertrophy. The effects of irisin on hypertrophy are due to activation of satellite cells and enhanced protein synthesis. In addition, irisin injection rescues loss of skeletal muscle mass following denervation by enhancing satellite cell activation and reducing protein degradation. These data suggest that irisin functions as a pro-myogenic factor in mice.

  15. Complete rupture of the distal semimembranosus tendon with secondary hamstring muscles atrophy: MR findings in two cases

    International Nuclear Information System (INIS)

    Varela, J.R.; Rodriguez, E.; Soler, R.; Gonzalez, J.; Pombo, S.

    2000-01-01

    Complete rupture of the hamstring muscles is a rare injury. The proximal musculo-tendinous junction is the most frequent site of rupture. We present two cases of complete rupture of the distal semimenbranosus tendon, which clinically presented as soft-tissue masses. MR imaging permitted the correct diagnosis. There has been only one other such case reported. (orig.)

  16. Complete rupture of the distal semimembranosus tendon with secondary hamstring muscles atrophy: MR findings in two cases

    Energy Technology Data Exchange (ETDEWEB)

    Varela, J.R.; Rodriguez, E.; Soler, R.; Gonzalez, J.; Pombo, S. [Dept. of Radiology, Hospital Juan Canalejo, La Coruna (Spain)

    2000-06-01

    Complete rupture of the hamstring muscles is a rare injury. The proximal musculo-tendinous junction is the most frequent site of rupture. We present two cases of complete rupture of the distal semimenbranosus tendon, which clinically presented as soft-tissue masses. MR imaging permitted the correct diagnosis. There has been only one other such case reported. (orig.)

  17. IGF-1 attenuates hypoxia-induced atrophy but inhibits myoglobin expression in C2C12 skeletal muscle myotubes

    NARCIS (Netherlands)

    Peters, Eva L.; van der Linde, Sandra M.; Vogel, Ilse S.P.; Haroon, Mohammad; Offringa, Carla; de Wit, Gerard M.J.; Koolwijk, Pieter; van der Laarse, Willem J.; Jaspers, Richard T.

    2017-01-01

    Chronic hypoxia is associated with muscle wasting and decreased oxidative capacity. By contrast, training under hypoxia may enhance hypertrophy and increase oxidative capacity as well as oxygen transport to the mitochondria, by increasing myoglobin (Mb) expression. The latter may be a feasible

  18. Antioxidants for preventing and reducing muscle soreness after exercise.

    Science.gov (United States)

    Ranchordas, Mayur K; Rogerson, David; Soltani, Hora; Costello, Joseph T

    2017-12-14

    Muscle soreness typically occurs after intense exercise, unaccustomed exercise or actions that involve eccentric contractions where the muscle lengthens while under tension. It peaks between 24 and 72 hours after the initial bout of exercise. Many people take antioxidant supplements or antioxidant-enriched foods before and after exercise in the belief that these will prevent or reduce muscle soreness after exercise. To assess the effects (benefits and harms) of antioxidant supplements and antioxidant-enriched foods for preventing and reducing the severity and duration of delayed onset muscle soreness following exercise. We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register, the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, SPORTDiscus, trial registers, reference lists of articles and conference proceedings up to February 2017. We included randomised and quasi-randomised controlled trials investigating the effects of all forms of antioxidant supplementation including specific antioxidant supplements (e.g. tablets, powders, concentrates) and antioxidant-enriched foods or diets on preventing or reducing delayed onset muscle soreness (DOMS). We excluded studies where antioxidant supplementation was combined with another supplement. Two review authors independently screened search results, assessed risk of bias and extracted data from included trials using a pre-piloted form. Where appropriate, we pooled results of comparable trials, generally using the random-effects model. The outcomes selected for presentation in the 'Summary of findings' table were muscle soreness, collected at times up to 6 hours, 24, 48, 72 and 96 hours post-exercise, subjective recovery and adverse effects. We assessed the quality of the evidence using GRADE. Fifty randomised, placebo-controlled trials were included, 12 of which used a cross-over design. Of the 1089 participants, 961 (88.2%) were male and 128 (11.8%) were female. The age range for

  19. Estimulação elétrica neuromuscular em cães com atrofia muscular induzida Neuromuscular electric stimulation in dogs with induced muscle atrophy

    Directory of Open Access Journals (Sweden)

    C. Pelizzari

    2008-02-01

    Full Text Available Empregou-se a estimulação elétrica neuromuscular (EENM de baixa freqüência no músculo quadríceps femoral de cães com atrofia induzida e avaliou-se a ocorrência de ganho de massa nessa musculatura. Foram utilizados oito cães com pesos entre 15 e 30kg, distribuídos aleatoriamente em dois grupos denominados de I ou controle e II ou tratado. A articulação femorotibiopatelar esquerda foi imobilizada por 30 dias pelo método de transfixação percutânea tipo II, com retirada de aparelho de imobilização após esse período. Decorridas 48 horas da remoção, foi realizada a EENM nos cães do grupo II, cinco vezes por semana, com intervalo de 24 horas cada sessão, pelo período de 60 dias. Foram avaliadas a circunferência da coxa, a goniometria do joelho, a análise clínica da marcha, as enzimas creatina-quinase (CK e aspartato-amino-transferase (AST e a morfometria das fibras musculares em cortes transversais do músculo vasto lateral colhido mediante biópsia muscular. A EENM foi empregada no músculo quadríceps femoral na freqüência de 50Hz, duração de pulso de 300 milisegundos e relação de tempo on/off de 1:2. Quanto à morfometria das fibras do músculo vasto lateral, no grupo tratado houve aumento significativo (PLow frequency neuromuscular electrical stimulation (NMES was used on the femoral quadriceps of dogs with induced muscular atrophy and the occurrence of gain in mass in these muscles was evaluated. Eight dogs from 15 to 30kg were randomly distributed in two groups named I, or control; and II, or treated. For the induction of muscular atrophy, the left femoral-tibial-patellar joint was immobilized for 30 days by percutaneous transfixation type II. After 30 days, the immobilization device was removed. The NMES treatment began 48 hours after the removal of the immobilization device of the dogs of group II, and it was carried out five times per week with an interval of 24 hours between each session, for 60 days. The

  20. Effect of electrical muscle stimulation on prevention of ICU acquired ...

    African Journals Online (AJOL)

    Hassan Abdelaziz Abu-Khaber

    2013-04-19

    Apr 19, 2013 ... shown to increase after an EMS session in rat skeletal muscles.10, ... output, and therefore affect the skeletal muscle metabolism .... Grade 1 No active range of motion & palpable muscle contraction. Grade 0 No active range of motion & no palpable muscle contraction. Table 1 Functions assessed in MRCS.

  1. Association between muscle atrophy/weakness and health care costs and utilization among patients receiving total knee replacement surgery: a retrospective cohort study

    Directory of Open Access Journals (Sweden)

    Chen SY

    2013-08-01

    Full Text Available Shih-Yin Chen,1 Ning Wu,1 Yuan-Chi Lee,1 Yang Zhao21Health Economics and Epidemiology, Evidera, Lexington, Massachusetts, 2Health Economics and Outcomes Research, Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USAPurpose: The aim of the study reported here was to examine health care resource utilization, costs, and risk of rehospitalization for total knee replacement (TKR patients with and without muscle atrophy/weakness (MAW.Patients and methods: Individuals aged 50–64 years with commercial insurance or 65+ years with Medicare Supplemental Insurance (Medicare who had a hospitalization for TKR between January 1, 2006 and September 30, 2009 were identified from a large US claims database. First hospitalization for TKR was defined as the index stay. All patients were classified into three cohorts according to when MAW was diagnosed relative to TKR: pre-MAW, post-MAW, and no MAW. The association between MAW and health care costs over the 12-month post-index period and the probability of rehospitalization were assessed via multivariate regressions.Results: The study sample included 53,696 Medicare and 46,058 commercial insurance TKR patients. Controlling for cross-cohort differences, both the pre- and post-MAW cohorts had significantly higher total health care costs (Medicare US$4,201 and US$9,404 higher, commercial insurance US$2,737 and US$6,640 higher, respectively than the no MAW cohort (all P < 0.05. The post-MAW cohort in both populations was also more likely to have any all-cause or replacement-related rehospitalization compared with the no MAW cohort.Conclusion: Among US patients undergoing TKR, those with MAW had higher health care utilization and costs than patients without MAW.Keywords: rehospitalization, resource utilization, Medicare, health insurance, USA

  2. 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

  3. Postoperative respiratory muscle dysfunction: pathophysiology and preventive strategies.

    Science.gov (United States)

    Sasaki, Nobuo; Meyer, Matthew J; Eikermann, Matthias

    2013-04-01

    Postoperative pulmonary complications are responsible for significant increases in hospital cost as well as patient morbidity and mortality; respiratory muscle dysfunction represents a contributing factor. Upper airway dilator muscles functionally resist the upper airway collapsing forces created by the respiratory pump muscles. Standard perioperative medications (anesthetics, sedatives, opioids, and neuromuscular blocking agents), interventions (patient positioning, mechanical ventilation, and surgical trauma), and diseases (lung hyperinflation, obesity, and obstructive sleep apnea) have differential effects on the respiratory muscle subgroups. These effects on the upper airway dilators and respiratory pump muscles impair their coordination and function and can result in respiratory failure. Perioperative management strategies can help decrease the incidence of postoperative respiratory muscle dysfunction. Such strategies include minimally invasive procedures rather than open surgery, early and optimal mobilizing of respiratory muscles while on mechanical ventilation, judicious use of respiratory depressant anesthetics and neuromuscular blocking agents, and noninvasive ventilation when possible.

  4. The Importance of Trunk Muscle Strength for Balance, Functional Performance, and Fall Prevention in Seniors : A Systematic Review

    NARCIS (Netherlands)

    Granacher, Urs; Gollhofer, Albert; Hortobagyi, Tibor; Kressig, Reto W.; Muehlbauer, Thomas

    Background The aging process results in a number of functional (e.g., deficits in balance and strength/power performance), neural (e.g., loss of sensory/motor neurons), muscular (e.g., atrophy of type-II muscle fibers in particular), and bone-related (e.g., osteoporosis) deteriorations.

  5. 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.

  6. Growth hormone secretagogues prevent dysregulation of skeletal muscle calcium homeostasis in a rat model of cisplatin-induced cachexia.

    Science.gov (United States)

    Conte, Elena; Camerino, Giulia Maria; Mele, Antonietta; De Bellis, Michela; Pierno, Sabata; Rana, Francesco; Fonzino, Adriano; Caloiero, Roberta; Rizzi, Laura; Bresciani, Elena; Ben Haj Salah, Khoubaib; Fehrentz, Jean-Alain; Martinez, Jean; Giustino, Arcangela; Mariggiò, Maria Addolorata; Coluccia, Mauro; Tricarico, Domenico; Lograno, Marcello Diego; De Luca, Annamaria; Torsello, Antonio; Conte, Diana; Liantonio, Antonella

    2017-06-01

    Cachexia is a wasting condition associated with cancer types and, at the same time, is a serious and dose-limiting side effect of cancer chemotherapy. Skeletal muscle loss is one of the main characteristics of cachexia that significantly contributes to the functional muscle impairment. Calcium-dependent signaling pathways are believed to play an important role in skeletal muscle decline observed in cachexia, but whether intracellular calcium homeostasis is affected in this situation remains uncertain. Growth hormone secretagogues (GHS), a family of synthetic agonists of ghrelin receptor (GHS-R1a), are being developed as a therapeutic option for cancer cachexia syndrome; however, the exact mechanism by which GHS interfere with skeletal muscle is not fully understood. By a multidisciplinary approach ranging from cytofluorometry and electrophysiology to gene expression and histology, we characterized the calcium homeostasis in fast-twitch extensor digitorum longus (EDL) muscle of adult rats with cisplatin-induced cachexia and established the potential beneficial effects of two GHS (hexarelin and JMV2894) at this level. Additionally, in vivo measures of grip strength and of ultrasonography recordings allowed us to evaluate the functional impact of GHS therapeutic intervention. Cisplatin-treated EDL muscle fibres were characterized by a ~18% significant reduction of the muscle weight and fibre diameter together with an up-regulation of atrogin1/Murf-1 genes and a down-regulation of Pgc1-a gene, all indexes of muscle atrophy, and by a two-fold increase in resting intracellular calcium, [Ca 2+ ] i , compared with control rats. Moreover, the amplitude of the calcium transient induced by caffeine or depolarizing high potassium solution as well as the store-operated calcium entry were ~50% significantly reduced in cisplatin-treated rats. Calcium homeostasis dysregulation parallels with changes of functional ex vivo (excitability and resting macroscopic conductance) and in

  7. Role of Exercise Therapy in Prevention of Decline in Aging Muscle Function: Glucocorticoid Myopathy and Unloading

    Directory of Open Access Journals (Sweden)

    Teet Seene

    2012-01-01

    Full Text Available Changes in skeletal muscle quantity and quality lead to disability in the aging population. Physiological changes in aging skeletal muscle are associated with a decline in mass, strength, and inability to maintain balance. Glucocorticoids, which are in wide exploitation in various clinical scenarios, lead to the loss of the myofibrillar apparatus, changes in the extracellular matrix, and a decrease in muscle strength and motor activity, particularly in the elderly. Exercise therapy has shown to be a useful tool for the prevention of different diseases, including glucocorticoid myopathy and muscle unloading in the elderly. The purpose of the paper is to discuss the possibilities of using exercise therapy in the prevention of glucocorticoid caused myopathy and unloading in the elderly and to describe relationships between the muscle contractile apparatus and the extracellular matrix in different types of aging muscles.

  8. 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.

  9. The omega-3 fatty acid, eicosapentaenoic acid (EPA, prevents the damaging effects of tumour necrosis factor (TNF-alpha during murine skeletal muscle cell differentiation

    Directory of Open Access Journals (Sweden)

    Pearson Stephen

    2008-07-01

    Full Text Available Abstract Background Eicosapentaenoic acid (EPA is a ώ-3 polyunsaturated fatty acid with anti-inflammatory and anti-cachetic properties that may have potential benefits with regards to skeletal muscle atrophy conditions where inflammation is present. It is also reported that pathologic levels of the pro-inflammatory cytokine tumour necrosis factor (TNF-α are associated with muscle wasting, exerted through inhibition of myogenic differentiation and enhanced apoptosis. These findings led us to hypothesize that EPA may have a protective effect against skeletal muscle damage induced by the actions of TNF-α. Results The deleterious effects of TNF-α on C2C12 myogenesis were completely inhibited by co-treatment with EPA. Thus, EPA prevented the TNF-mediated loss of MyHC expression and significantly increased myogenic fusion (p p p p p p Conclusion In conclusion, EPA has a protective action against the damaging effects of TNF-α on C2C12 myogenesis. These findings support further investigations of EPA as a potential therapeutic agent during skeletal muscle regeneration following injury.

  10. Inhibition of platelet-derived growth factor signaling prevents muscle fiber growth during skeletal muscle hypertrophy.

    Science.gov (United States)

    Sugg, Kristoffer B; Korn, Michael A; Sarver, Dylan C; Markworth, James F; Mendias, Christopher L

    2017-03-01

    The platelet-derived growth factor receptors alpha and beta (PDGFRα and PDGFRβ) mark fibroadipogenic progenitor cells/fibroblasts and pericytes in skeletal muscle, respectively. While the role that these cells play in muscle growth and development has been evaluated, it was not known whether the PDGF receptors activate signaling pathways that control transcriptional and functional changes during skeletal muscle hypertrophy. To evaluate this, we inhibited PDGFR signaling in mice subjected to a synergist ablation muscle growth procedure, and performed analyses 3 and 10 days after induction of hypertrophy. The results from this study indicate that PDGF signaling is required for fiber hypertrophy, extracellular matrix production, and angiogenesis that occur during muscle growth. © 2017 Federation of European Biochemical Societies.

  11. 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...

  12. 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...

  13. 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.

  14. REGULATION OF AUTOPHAGY AND THE UBIQUITIN-€“ PROTEASOME SYSTEM BY THE FoxO TRANSCRIPTIONAL NETWORK DURING MUSCLE ATROPHY

    OpenAIRE

    PESCATORE, FRANCESCA

    2016-01-01

    Skeletal muscle can adapt its mass in response to physical activity, metabolism and hormones. The control of muscle size depends on the coordinated balance between protein synthesis and protein degradation. Mechanical overload or anabolic hormonal stimulation shifts the balance towards protein synthesis leading to an increase in fiber size, a process called hypertrophy. Conversely, in catabolic conditions protein degradation exceeds protein synthesis resulting into muscle weakness and muscle ...

  15. Selective androgen receptor modulators for the prevention and treatment of muscle wasting associated with cancer.

    Science.gov (United States)

    Dalton, James T; Taylor, Ryan P; Mohler, Michael L; Steiner, Mitchell S

    2013-12-01

    This review highlights selective androgen receptor modulators (SARMs) as emerging agents in late-stage clinical development for the prevention and treatment of muscle wasting associated with cancer. Muscle wasting, including a loss of skeletal muscle, is a cancer-related symptom that begins early in the progression of cancer and affects a patient's quality of life, ability to tolerate chemotherapy, and survival. SARMs increase muscle mass and improve physical function in healthy and diseased individuals, and potentially may provide a new therapy for muscle wasting and cancer cachexia. SARMs modulate the same anabolic pathways targeted with classical steroidal androgens, but within the dose range in which expected effects on muscle mass and function are seen androgenic side-effects on prostate, skin, and hair have not been observed. Unlike testosterone, SARMs are orally active, nonaromatizable, nonvirilizing, and tissue-selective anabolic agents. Recent clinical efficacy data for LGD-4033, MK-0773, MK-3984, and enobosarm (GTx-024, ostarine, and S-22) are reviewed. Enobosarm, a nonsteroidal SARM, is the most well characterized clinically, and has consistently demonstrated increases in lean body mass and better physical function across several populations along with a lower hazard ratio for survival in cancer patients. Completed in May 2013, results for the Phase III clinical trials entitled Prevention and treatment Of muscle Wasting in patiEnts with Cancer1 (POWER1) and POWER2 evaluating enobosarm for the prevention and treatment of muscle wasting in patients with nonsmall cell lung cancer will be available soon, and will potentially establish a SARM, enobosarm, as the first drug for the prevention and treatment of muscle wasting in cancer patients.

  16. 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

    soleus is also important for normal locomotion, we further performed a fatigue trial in the soleus and found that the decrease in relative force was greater and more rapid in solei from C-26 mice compared to controls. These data demonstrate that severe cancer cachexia causes profound muscle weakness that is not entirely explained by the muscle atrophy. In addition, cancer cachexia decreases the fatigue resistance of the soleus muscle, a postural muscle typically resistant to fatigue. Thus, specifically targeting contractile dysfunction represents an additional means to counter muscle weakness in cancer cachexia, in addition to targeting the prevention of muscle atrophy.

  17. 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

    soleus is also important for normal locomotion, we further performed a fatigue trial in the soleus and found that the decrease in relative force was greater and more rapid in solei from C-26 mice compared to controls. These data demonstrate that severe cancer cachexia causes profound muscle weakness that is not entirely explained by the muscle atrophy. In addition, cancer cachexia decreases the fatigue resistance of the soleus muscle, a postural muscle typically resistant to fatigue. Thus, specifically targeting contractile dysfunction represents an additional means to counter muscle weakness in cancer cachexia, in addition to targeting the prevention of muscle atrophy

  18. Isoinertial technology for rehabilitation and prevention of muscle injuries of soccer players: literature review

    OpenAIRE

    Prieto-Mondragón, Laura del Pilar; Camargo-Rojas, Diana Alexandra; Quiceno, Christian Alexander

    2016-01-01

    Abstract Introduction: Soccer is the sport with the highest risk of muscle injury for players. Eccentric exercise is fundamental for reducing injury rates and isoinertial technology devices cause an increase in eccentric demands after a concentric contraction. Objective: To identify the use of isoinertial technology in the fields of physical activity and sports for rehabilitation and prevention of muscle injuries reported in scientific literature. Materials and methods: A search of scienti...

  19. 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.

  20. 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.)

  1. 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.

  2. Muscle Cramps

    Science.gov (United States)

    ... Talk to your provider about the risks and benefits of medicines. How can I prevent muscle cramps? To prevent muscle cramps, you can Stretch your muscles, especially before exercising. If you often get leg cramps at night, ...

  3. Dominant optic atrophy

    Directory of Open Access Journals (Sweden)

    Lenaers Guy

    2012-07-01

    bilateral, mild, otherwise unexplained visual loss related to optic discs pallor or atrophy, and typically occurring in the context of a family history of DOA. Optical Coherence Tomography further discloses non-specific thinning of retinal nerve fiber layer, but a normal morphology of the photoreceptors layers. Abnormal visual evoked potentials and pattern ERG may also reflect the dysfunction of the RGCs and their axons. Molecular diagnosis is provided by the identification of a mutation in the OPA1 gene (75% of DOA patients or in the OPA3 gene (1% of patients. Prognosis Visual loss in DOA may progress during puberty until adulthood, with very slow subsequent chronic progression in most of the cases. On the opposite, in DOA patients with associated extra-ocular features, the visual loss may be more severe over time. Management To date, there is no preventative or curative treatment in DOA; severely visually impaired patients may benefit from low vision aids. Genetic counseling is commonly offered and patients are advised to avoid alcohol and tobacco consumption, as well as the use of medications that may interfere with mitochondrial metabolism. Gene and pharmacological therapies for DOA are currently under investigation.

  4. 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.)

  5. A multi-ingredient dietary supplement abolishes large-scale brain cell loss, improves sensory function, and prevents neuronal atrophy in aging mice.

    Science.gov (United States)

    Lemon, J A; Aksenov, V; Samigullina, R; Aksenov, S; Rodgers, W H; Rollo, C D; Boreham, D R

    2016-06-01

    Transgenic growth hormone mice (TGM) are a recognized model of accelerated aging with characteristics including chronic oxidative stress, reduced longevity, mitochondrial dysfunction, insulin resistance, muscle wasting, and elevated inflammatory processes. Growth hormone/IGF-1 activate the Target of Rapamycin known to promote aging. TGM particularly express severe cognitive decline. We previously reported that a multi-ingredient dietary supplement (MDS) designed to offset five mechanisms associated with aging extended longevity, ameliorated cognitive deterioration and significantly reduced age-related physical deterioration in both normal mice and TGM. Here we report that TGM lose more than 50% of cells in midbrain regions, including the cerebellum and olfactory bulb. This is comparable to severe Alzheimer's disease and likely explains their striking age-related cognitive impairment. We also demonstrate that the MDS completely abrogates this severe brain cell loss, reverses cognitive decline and augments sensory and motor function in aged mice. Additionally, histological examination of retinal structure revealed markers consistent with higher numbers of photoreceptor cells in aging and supplemented mice. We know of no other treatment with such efficacy, highlighting the potential for prevention or amelioration of human neuropathologies that are similarly associated with oxidative stress, inflammation and cellular dysfunction. Environ. Mol. Mutagen. 57:382-404, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  6. 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.

  7. Skeletal muscle gene expression after myostatin knockout in mature mice Address for reprint requests and other correspondence: S. Welle, Univ. of Rochester Medical Center, 601 Elmwood Ave., Box 693, Rochester, NY 14642 (e-mail: ).

    OpenAIRE

    Welle, Stephen; Cardillo, Andrew; Zanche, Michelle; Tawil, Rabi

    2009-01-01

    There is much interest in developing anti-myostatin agents to reverse or prevent muscle atrophy in adults, so it is important to characterize the effects of reducing myostatin activity after normal muscle development. For assessment of the effect of loss of myostatin signaling on gene expression in muscle, RNA from mice with postdevelopmental myostatin knockout was analyzed with oligonucleotide microarrays. Myostatin was undetectable in muscle within 2 wk after Cre recombinase activation in 4...

  8. High-intensity interval training prevents oxidant-mediated diaphragm muscle weakness in hypertensive mice.

    Science.gov (United States)

    Bowen, T Scott; Eisenkolb, Sophia; Drobner, Juliane; Fischer, Tina; Werner, Sarah; Linke, Axel; Mangner, Norman; Schuler, Gerhard; Adams, Volker

    2017-01-01

    Hypertension is a key risk factor for heart failure, with the latter characterized by diaphragm muscle weakness that is mediated in part by increased oxidative stress. In the present study, we used a deoxycorticosterone acetate (DOCA)-salt mouse model to determine whether hypertension could independently induce diaphragm dysfunction and further investigated the effects of high-intensity interval training (HIIT). Sham-treated (n = 11), DOCA-salt-treated (n = 11), and DOCA-salt+HIIT-treated (n = 15) mice were studied over 4 wk. Diaphragm contractile function, protein expression, enzyme activity, and fiber cross-sectional area and type were subsequently determined. Elevated blood pressure confirmed hypertension in DOCA-salt mice independent of HIIT (P HIIT. Myosin heavy chain (MyHC) protein expression tended to decrease (∼30%; P = 0.06) in DOCA-salt vs. sham- and DOCA-salt+HIIT mice, whereas oxidative stress increased (P HIIT further prevented direct oxidant-mediated diaphragm contractile dysfunction (P hypertension induces diaphragm contractile dysfunction via an oxidant-mediated mechanism that is prevented by HIIT.-Bowen, T. S., Eisenkolb, S., Drobner, J., Fischer, T., Werner, S., Linke, A., Mangner, N., Schuler, G., Adams, V. High-intensity interval training prevents oxidant-mediated diaphragm muscle weakness in hypertensive mice. © FASEB.

  9. 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.

  10. 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.

  11. 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

  12. 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.

  13. Survival motor neuron protein in motor neurons determines synaptic integrity in spinal muscular atrophy.

    Science.gov (United States)

    Martinez, Tara L; Kong, Lingling; Wang, Xueyong; Osborne, Melissa A; Crowder, Melissa E; Van Meerbeke, James P; Xu, Xixi; Davis, Crystal; Wooley, Joe; Goldhamer, David J; Lutz, Cathleen M; Rich, Mark M; Sumner, Charlotte J

    2012-06-20

    The inherited motor neuron disease spinal muscular atrophy (SMA) is caused by deficient expression of survival motor neuron (SMN) protein and results in severe muscle weakness. In SMA mice, synaptic dysfunction of both neuromuscular junctions (NMJs) and central sensorimotor synapses precedes motor neuron cell death. To address whether this synaptic dysfunction is due to SMN deficiency in motor neurons, muscle, or both, we generated three lines of conditional SMA mice with tissue-specific increases in SMN expression. All three lines of mice showed increased survival, weights, and improved motor behavior. While increased SMN expression in motor neurons prevented synaptic dysfunction at the NMJ and restored motor neuron somal synapses, increased SMN expression in muscle did not affect synaptic function although it did improve myofiber size. Together these data indicate that both peripheral and central synaptic integrity are dependent on motor neurons in SMA, but SMN may have variable roles in the maintenance of these different synapses. At the NMJ, it functions at the presynaptic terminal in a cell-autonomous fashion, but may be necessary for retrograde trophic signaling to presynaptic inputs onto motor neurons. Importantly, SMN also appears to function in muscle growth and/or maintenance independent of motor neurons. Our data suggest that SMN plays distinct roles in muscle, NMJs, and motor neuron somal synapses and that restored function of SMN at all three sites will be necessary for full recovery of muscle power.

  14. Disruption of TGF-β signaling in smooth muscle cell prevents flow-induced vascular remodeling

    Energy Technology Data Exchange (ETDEWEB)

    Gao, Fu [Department of Vascular Surgery, Peking University People’s Hospital, Beijing (China); Chambon, Pierre [Institut de Génétique et de Biologie Moléculaire et Cellulaire (CNRS UMR7104, INSERM U596, ULP, Collége de France) and Institut Clinique de la Souris, ILLKIRCH, Strasbourg (France); Tellides, George [Department of Surgery, Interdepartmental Program in Vascular Biology and Therapeutics, Yale University School of Medicine, New Haven, CT (United States); Kong, Wei [Department of Physiology and Pathophysiology, Basic Medical College of Peking University, Beijing (China); Zhang, Xiaoming, E-mail: rmygxgwk@163.com [Department of Vascular Surgery, Peking University People’s Hospital, Beijing (China); Li, Wei [Department of Vascular Surgery, Peking University People’s Hospital, Beijing (China)

    2014-11-07

    Highlights: • TGF-β signaling in SMC contributes to the flow-induced vascular remodeling. • Disruption of TGF-β signaling in SMC can prevent this process. • Targeting SM-specific Tgfbr2 could be a novel therapeutic strategy for vascular remodeling. - Abstract: Transforming growth factor-β (TGF-β) signaling has been prominently implicated in the pathogenesis of vascular remodeling, especially the initiation and progression of flow-induced vascular remodeling. Smooth muscle cells (SMCs) are the principal resident cells in arterial wall and are critical for arterial remodeling. However, the role of TGF-β signaling in SMC for flow-induced vascular remodeling remains unknown. Therefore, the goal of our study was to determine the effect of TGF-β pathway in SMC for vascular remodeling, by using a genetical smooth muscle-specific (SM-specific) TGF-β type II receptor (Tgfbr2) deletion mice model. Mice deficient in the expression of Tgfbr2 (MyhCre.Tgfbr2{sup f/f}) and their corresponding wild-type background mice (MyhCre.Tgfbr2{sup WT/WT}) underwent partial ligation of left common carotid artery for 1, 2, or 4 weeks. Then the carotid arteries were harvested and indicated that the disruption of Tgfbr2 in SMC provided prominent inhibition of vascular remodeling. And the thickening of carotid media, proliferation of SMC, infiltration of macrophage, and expression of matrix metalloproteinase (MMP) were all significantly attenuated in Tgfbr2 disruption mice. Our study demonstrated, for the first time, that the TGF-β signaling in SMC plays an essential role in flow-induced vascular remodeling and disruption can prevent this process.

  15. Lecithin Prevents Cortical Cytoskeleton Reorganization in Rat Soleus Muscle Fibers under Short-Term Gravitational Disuse.

    Directory of Open Access Journals (Sweden)

    Irina V Ogneva

    Full Text Available The aim of this study was to prevent the cortical cytoskeleton reorganization of rat soleus muscle fibers under short-term gravitational disuse. Once a day, we injected the right soleus muscle with 0.5 ml lecithin at a concentration of 200 mg/ml and the left soleus muscle with a diluted solution in an equal volume for 3 days prior to the experiment. To simulate microgravity conditions in rats, an anti-orthostatic suspension was used according to the Ilyin-Novikov method modified by Morey-Holton et al. for 6 hours. The following groups of soleus muscle tissues were examined: "C", "C+L", "HS", and "HS+L". The transversal stiffness of rat soleus muscle fibers after 6 hours of suspension did not differ from that of the control group for the corresponding legs; there were no differences between the groups without lecithin «C» and «HS» or between the groups with lecithin "C+L" and "HS+L". However, lecithin treatment for three days resulted in an increase in cell stiffness; in the "C+L" group, cell stiffness was significantly higher by 22.7% (p < 0.05 compared with that of group "C". The mRNA content of genes encoding beta- and gamma-actin and beta-tubulin did not significantly differ before and after suspension in the corresponding groups. However, there was a significant increase in the mRNA content of these genes after lecithin treatment: the beta-actin and gamma-actin mRNA content in group "C+L" increased by 200% compared with that of group "C", and beta-tubulin increased by 100% (as well as the mRNA content of tubulin-binding proteins Ckap5, Tcp1, Cct5 and Cct7. In addition, desmin mRNA content remained unchanged in all of the experimental groups. As a result of the lecithin injections, there was a redistribution of the mRNA content of genes encoding actin monomer- and filament-binding proteins in the direction of increasing actin polymerization and filament stability; the mRNA content of Arpc3 and Lcp1 increased by 3- and 5-fold, respectively

  16. Lecithin Prevents Cortical Cytoskeleton Reorganization in Rat Soleus Muscle Fibers under Short-Term Gravitational Disuse

    Science.gov (United States)

    Biryukov, Nikolay S.

    2016-01-01

    The aim of this study was to prevent the cortical cytoskeleton reorganization of rat soleus muscle fibers under short-term gravitational disuse. Once a day, we injected the right soleus muscle with 0.5 ml lecithin at a concentration of 200 mg/ml and the left soleus muscle with a diluted solution in an equal volume for 3 days prior to the experiment. To simulate microgravity conditions in rats, an anti-orthostatic suspension was used according to the Ilyin-Novikov method modified by Morey-Holton et al. for 6 hours. The following groups of soleus muscle tissues were examined: «C», «C+L», «HS», and «HS+L». The transversal stiffness of rat soleus muscle fibers after 6 hours of suspension did not differ from that of the control group for the corresponding legs; there were no differences between the groups without lecithin «C» and «HS» or between the groups with lecithin «C+L» and «HS+L». However, lecithin treatment for three days resulted in an increase in cell stiffness; in the «C+L» group, cell stiffness was significantly higher by 22.7% (p lecithin treatment: the beta-actin and gamma-actin mRNA content in group «C+L» increased by 200% compared with that of group «C», and beta-tubulin increased by 100% (as well as the mRNA content of tubulin-binding proteins Ckap5, Tcp1, Cct5 and Cct7). In addition, desmin mRNA content remained unchanged in all of the experimental groups. As a result of the lecithin injections, there was a redistribution of the mRNA content of genes encoding actin monomer- and filament-binding proteins in the direction of increasing actin polymerization and filament stability; the mRNA content of Arpc3 and Lcp1 increased by 3- and 5-fold, respectively, but the levels of Tmod1 and Svil decreased by 2- and 5-fold, respectively. However, gravitational disuse did not result in changes in the mRNA content of Arpc3, Tmod1, Svil or Lcp1. Anti-orthostatic suspension for 6 hours resulted in a decrease in the mRNA content of alpha

  17. Lecithin Prevents Cortical Cytoskeleton Reorganization in Rat Soleus Muscle Fibers under Short-Term Gravitational Disuse.

    Science.gov (United States)

    Ogneva, Irina V; Biryukov, Nikolay S

    2016-01-01

    The aim of this study was to prevent the cortical cytoskeleton reorganization of rat soleus muscle fibers under short-term gravitational disuse. Once a day, we injected the right soleus muscle with 0.5 ml lecithin at a concentration of 200 mg/ml and the left soleus muscle with a diluted solution in an equal volume for 3 days prior to the experiment. To simulate microgravity conditions in rats, an anti-orthostatic suspension was used according to the Ilyin-Novikov method modified by Morey-Holton et al. for 6 hours. The following groups of soleus muscle tissues were examined: "C", "C+L", "HS", and "HS+L". The transversal stiffness of rat soleus muscle fibers after 6 hours of suspension did not differ from that of the control group for the corresponding legs; there were no differences between the groups without lecithin «C» and «HS» or between the groups with lecithin "C+L" and "HS+L". However, lecithin treatment for three days resulted in an increase in cell stiffness; in the "C+L" group, cell stiffness was significantly higher by 22.7% (p lecithin treatment: the beta-actin and gamma-actin mRNA content in group "C+L" increased by 200% compared with that of group "C", and beta-tubulin increased by 100% (as well as the mRNA content of tubulin-binding proteins Ckap5, Tcp1, Cct5 and Cct7). In addition, desmin mRNA content remained unchanged in all of the experimental groups. As a result of the lecithin injections, there was a redistribution of the mRNA content of genes encoding actin monomer- and filament-binding proteins in the direction of increasing actin polymerization and filament stability; the mRNA content of Arpc3 and Lcp1 increased by 3- and 5-fold, respectively, but the levels of Tmod1 and Svil decreased by 2- and 5-fold, respectively. However, gravitational disuse did not result in changes in the mRNA content of Arpc3, Tmod1, Svil or Lcp1. Anti-orthostatic suspension for 6 hours resulted in a decrease in the mRNA content of alpha-actinin-4 (Actn4) and

  18. Effectiveness of muscle strengthening and description of protocols for preventing falls in the elderly: a systematic review

    Directory of Open Access Journals (Sweden)

    Erika Y. Ishigaki

    2014-05-01

    Full Text Available Background: Falls are a geriatric syndrome that is considered a significant public health problem in terms of morbidity and mortality because they lead to a decline in functional capacity and an impaired quality of life in the elderly. Lower limb muscle strengthening seems to be an effective intervention for preventing falls; however, there is no consensus regarding the best method for increasing lower limb muscle strength. Objectives: To analyze the effectiveness of lower limb muscle strengthening and to investigate and describe the protocols used for preventing falls in elderly subjects. Method: We performed a systematic review of randomized and controlled clinical trials published between 2002 and 2012 in the databases PubMed, EMBASE, Scopus, Web of Science, and PEDro that cited some type of lower limb muscle strengthening protocol and that evaluated the incidence of falls as the primary outcome exclusively in elderly subjects. Twelve studies met the inclusion criteria. Qualitative analysis was performed by independent reviewers applying the PEDro scale. Results: The data obtained from the selected studies showed lower fall rates in the intervention groups compared to controls. Six studies described the lower limb muscle strengthening protocol in detail. High methodological quality was found in 6 studies (PEDro score ≥7/10 points. Conclusions: The methodological quality of the studies in this area appears to leave little doubt regarding the effectiveness of lower limb strengthening exercises for preventing falls in elderly subjects, however the interventions in these studies were poorly reported.

  19. Pelvic floor muscle training in the prevention and treatment of urinary incontinence in women - what is the evidence?

    DEFF Research Database (Denmark)

    Brostrøm, Søren; Lose, G.

    2008-01-01

    Many women suffer from urinary incontinence (UI). During and after pregnancy, women are advised to perform pelvic floor muscle training (PFMT) to prevent the development of UI. In established UI, PFMT is prescribed routinely as first-line treatment. Published studies are small, underpowered...

  20. 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

  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. Activation of lower back muscles via FES for pressure sores prevention in paraplegia: a case study.

    Science.gov (United States)

    Vanoncini, M; Holderbaum, W; Andrews, B J

    2010-04-01

    The aim of this paper is to show the feasibility of the use of functional electrical stimulation (FES) applied to the lower back muscles for pressure sores prevention in paraplegia. The hypothesis under study is that FES induces a change in the pressure distribution on the contact area during sitting. Tests were conducted on a paraplegic subject (T5), sitting on a standard wheelchair and cushion. Trunk extensors (mainly the erector spinae) were stimulated using surface electrodes placed on the skin. A pressure mapping system was used to measure the pressure on the sitting surface in four situations: (a) no stimulation; (b) stimulation on one side of the spine only; (c) stimulation on both sides, at different levels; and (d) stimulation at the same level on both sides, during pressure-relief manoeuvres. A session of prolonged stimulation was also conducted. The experimental results show that the stimulation of the erector spinae on one side of the spine can induce a trunk rotation on the sagittal plane, which causes a change in the pressure distribution. A decrease of pressure on the side opposite to the stimulation was recorded. The phenomenon is intensified when different levels of stimulation are applied to the two sides, and such change can be sustained for a considerable time (around 5 minutes). The stimulation did not induce changes during pressure-relief manoeuvres. Finally, from this research we can conclude that the stimulation of the trunk extensors can be a useful tool for pressure sores prevention, and can potentially be used in a routine for pressure sores prevention based on periodical weight shifts.

  3. A subpopulation of smooth muscle cells, derived from melanocyte-competent precursors, prevents patent ductus arteriosus.

    Directory of Open Access Journals (Sweden)

    Ichiro Yajima

    Full Text Available BACKGROUND: Patent ductus arteriosus is a life-threatening condition frequent in premature newborns but also present in some term infants. Current mouse models of this malformation generally lead to perinatal death, not reproducing the full phenotypic spectrum in humans, in whom genetic inheritance appears complex. The ductus arteriosus (DA, a temporary fetal vessel that bypasses the lungs by shunting the aortic arch to the pulmonary artery, is constituted by smooth muscle cells of distinct origins (SMC1 and SMC2 and many fewer melanocytes. To understand novel mechanisms preventing DA closure at birth, we evaluated the importance of cell fate specification in SMC that form the DA during embryonic development. Upon specific Tyr::Cre-driven activation of Wnt/β-catenin signaling at the time of cell fate specification, melanocytes replaced the SMC2 population of the DA, suggesting that SMC2 and melanocytes have a common precursor. The number of SMC1 in the DA remained similar to that in controls, but insufficient to allow full DA closure at birth. Thus, there was no cellular compensation by SMC1 for the loss of SMC2. Mice in which only melanocytes were genetically ablated after specification from their potential common precursor with SMC2, demonstrated that differentiated melanocytes themselves do not affect DA closure. Loss of the SMC2 population, independent of the presence of melanocytes, is therefore a cause of patent ductus arteriosus and premature death in the first months of life. Our results indicate that patent ductus arteriosus can result from the insufficient differentiation, proliferation, or contractility of a specific smooth muscle subpopulation that shares a common neural crest precursor with cardiovascular melanocytes.

  4. A Subpopulation of Smooth Muscle Cells, Derived from Melanocyte-Competent Precursors, Prevents Patent Ductus Arteriosus

    Science.gov (United States)

    Puig, Isabel; Champeval, Delphine; Kumasaka, Mayuko; Belloir, Elodie; Bonaventure, Jacky; Mark, Manuel; Yamamoto, Hiroaki; Taketo, Mark M.; Choquet, Philippe; Etchevers, Heather C.; Beermann, Friedrich; Delmas, Véronique; Monassier, Laurent; Larue, Lionel

    2013-01-01

    Background Patent ductus arteriosus is a life-threatening condition frequent in premature newborns but also present in some term infants. Current mouse models of this malformation generally lead to perinatal death, not reproducing the full phenotypic spectrum in humans, in whom genetic inheritance appears complex. The ductus arteriosus (DA), a temporary fetal vessel that bypasses the lungs by shunting the aortic arch to the pulmonary artery, is constituted by smooth muscle cells of distinct origins (SMC1 and SMC2) and many fewer melanocytes. To understand novel mechanisms preventing DA closure at birth, we evaluated the importance of cell fate specification in SMC that form the DA during embryonic development. Upon specific Tyr::Cre-driven activation of Wnt/β-catenin signaling at the time of cell fate specification, melanocytes replaced the SMC2 population of the DA, suggesting that SMC2 and melanocytes have a common precursor. The number of SMC1 in the DA remained similar to that in controls, but insufficient to allow full DA closure at birth. Thus, there was no cellular compensation by SMC1 for the loss of SMC2. Mice in which only melanocytes were genetically ablated after specification from their potential common precursor with SMC2, demonstrated that differentiated melanocytes themselves do not affect DA closure. Loss of the SMC2 population, independent of the presence of melanocytes, is therefore a cause of patent ductus arteriosus and premature death in the first months of life. Our results indicate that patent ductus arteriosus can result from the insufficient differentiation, proliferation, or contractility of a specific smooth muscle subpopulation that shares a common neural crest precursor with cardiovascular melanocytes. PMID:23382837

  5. 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

    relengthening of a chronically retracted musculotendinous unit is feasible and advances the retracted musculotendinous junction toward its original position. This does not change the muscle work capacity. Whereas anabolic steroids have been shown to be effective in preventing classic degenerative muscle changes after tendon tears, neither an anabolic steroid nor IGF contributes to regeneration of the muscle once degenerative changes are established. The findings demonstrate that muscle cells lose reactiveness to an anabolic steroid and IGF once retraction has led to fatty infiltration and atrophy of the muscle. Retraction of the muscle after tendon tears must be avoided by early repair, particularly in an athlete, as no regeneration can be achieved by mechanical or pharmacological means at this time.

  6. Biceps-Related Physical Findings Are Useful to Prevent Misdiagnosis of Cervical Spondylotic Amyotrophy as a Rotator Cuff Tear.

    Science.gov (United States)

    Iwata, Eiichiro; Shigematsu, Hideki; Inoue, Kazuya; Egawa, Takuya; Tanaka, Masato; Okuda, Akinori; Morimoto, Yasuhiko; Masuda, Keisuke; Yamamoto, Yusuke; Sakamoto, Yoshihiro; Koizumi, Munehisa; Tanaka, Yasuhito

    2018-02-01

    Case-control study. The aim of the present study was to identify physical findings useful for differentiating between cervical spondylotic amyotrophy (CSA) and rotator cuff tears to prevent the misdiagnosis of CSA as a rotator cuff tear. CSA and rotator cuff tears are often confused among patients presenting with difficulty in shoulder elevation. Twenty-five patients with CSA and 27 with rotator cuff tears were enrolled. We included five physical findings specific to CSA that were observed in both CSA and rotator cuff tear patients. The findings were as follows: (1) weakness of the deltoid muscle, (2) weakness of the biceps muscle, (3) atrophy of the deltoid muscle, (4) atrophy of the biceps muscle, and (5) swallow-tail sign (assessment of the posterior fibers of the deltoid). Among 25 CSA patients, 10 (40.0%) were misdiagnosed with a rotator cuff tear on initial diagnosis. The sensitivity and specificity of each physical finding were as follows: (1) deltoid weakness (sensitivity, 92.0%; specificity, 55.6%), (2) biceps weakness (sensitivity, 80.0%; specificity, 100%), (3) deltoid atrophy (sensitivity, 96.0%; specificity, 77.8%), (4) biceps atrophy (sensitivity, 88.8%; specificity, 92.6%), and (5) swallow-tail sign (sensitivity, 56.0%; specificity, 74.1%). There were statistically significant differences in each physical finding. CSA is likely to be misdiagnosed as a rotator cuff tear; however, weakness and atrophy of the biceps are useful findings for differentiating between CSA and rotator cuff tears to prevent misdiagnosis.

  7. 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

  8. 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

  9. Preventive Effects of Eccentric Training on Acute Hamstring Muscle Injury in Professional Baseball

    Science.gov (United States)

    Seagrave, Richard A.; Perez, Luis; McQueeney, Sean; Toby, E. Bruce; Key, Vincent; Nelson, Joshua D.

    2014-01-01

    Background: Hamstring injuries are the second most common injury causing missed days in professional baseball field players. Recent studies have shown the preventive benefit of eccentric conditioning on the hamstring muscle group in injury prevention. Specifically, Nordic-type exercises have been shown to decrease the incidence of acute hamstring injuries in professional athletes. Purpose: This was a prospective study performed in coordination with a single Major League Baseball (MLB) organization (major and minor league teams) that targeted the effects of Nordic exercises on the incidence of acute hamstring injuries in the professional-level baseball player. Study Design: Prospective cohort study; Level of evidence, 2. Methods: The daily workouts of 283 professional baseball players throughout all levels of a single MLB organization were prospectively recorded. The intervention group participated in the Nordic exercise program and was compared with a randomly selected control group of professional athletes within the organization not participating in the exercise program. The incidence of hamstring injuries in both groups was compared, and the total number of days missed due to injury was compared with the 2 previous seasons. Results: There were 10 hamstring injuries that occurred during the 2012 season among the 283 professional athletes that required removal from play. There were no injuries that occurred in the intervention group (n = 65, 0.00%; P = .0381). The number needed to treat (NNT) to prevent 1 hamstring injury was 11.3. The average repetitions per week of the injured group were assessed at multiple time points (2, 4, 6, and total weeks) prior to injury. There were significantly fewer repetitions per week performed in the injured group at all time points compared with overall average repetitions per week in the noninjured group (P = .0459, .0127, .0164, and .0299, respectively). After beginning the Nordic exercise program, there were 136 total days

  10. Herbs and natural supplements in the prevention and treatment of delayed-onset muscle soreness

    Directory of Open Access Journals (Sweden)

    Abbas Meamarbashi

    2017-01-01

    Full Text Available Objective:  Unaccustomed and intense eccentric exercise is a common cause of delayed-onset muscle soreness (DOMS. There are multiple remedies for the treatment of DOMS, but its clinical and laboratory pieces of evidence are scarce. Currently, the treatments proposed for DOMS are numerous and include pharmaceuticals, herbal remedies, stretching, massage, nutritional supplements, and other alternatives. To find a holistic treatment with effective pain relief and minimum side effects, complementary and alternative medicine, including herbal therapies, plays a main role.Methods: In this review, the existing published studies investigating the efficacy of herbal and natural supplementation therapies for the prevention or treatment of side effects, symptoms, and signs of DOMS are summarized.Results: Previous studies have documented the efficacy of herbal therapies to treat pain, inflammation, as well as laboratory and clinical side effects of DOMS.Conclusion: The use of herbs in DOMS seems safer and has lower side effects than pharmacotherapy. However, the potential for side effects and drug interactions should be considered.

  11. 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.

  12. Deletion of skeletal muscle SOCS3 prevents insulin resistance in obesity

    DEFF Research Database (Denmark)

    Beck Jørgensen, Sebastian; O'Neill, Hayley M; Sylow, Lykke

    2013-01-01

    Obesity is associated with chronic low-grade inflammation that contributes to defects in energy metabolism and insulin resistance. Suppressor of cytokine signaling (SOCS)-3 expression is increased in skeletal muscle of obese humans. SOCS3 inhibits leptin signaling in the hypothalamus and insulin...... of hyperinsulinemia and insulin resistance because of enhanced skeletal muscle insulin receptor substrate 1 (IRS1) and Akt phosphorylation that resulted in increased skeletal muscle glucose uptake. These data indicate that skeletal muscle SOCS3 does not play a critical role in regulating muscle development or energy...... expenditure, but it is an important contributing factor for inhibiting insulin sensitivity in obesity. Therapies aimed at inhibiting SOCS3 in skeletal muscle may be effective in reversing obesity-related glucose intolerance and insulin resistance....

  13. Cold-water immersion (cryotherapy for preventing and treating muscle soreness after exercise

    Directory of Open Access Journals (Sweden)

    Chris Bleakley

    Full Text Available BACKGROUND: Many strategies are in use with the intention of preventing or minimizing delayed onset muscle soreness and fatigue after exercise. Cold-water immersion, in water temperatures of less than 15 °C, is currently one of the most popular interventional strategies used after exercise. OBJECTIVES: To determine the effects of cold-water immersion in the management of muscle soreness after exercise. SEARCH METHODS: In February 2010, we searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register, the Cochrane Central Register of Controlled Trials (The Cochrane Library (2010, Issue 1, Medline, Embase, Cumulative Index to Nursing and Allied Health (CINAHL, British Nursing Index and archive (BNI, and the Physiotherapy Evidence Database (PEDro. We also searched the reference lists of articles, handsearched journals and conference proceedings and contacted experts. In November 2011, we updated the searches of Central (2011, Issue 4, Medline (up to November Week 3 2011, Embase (to 2011 Week 46 and CINAHL (to 28 November 2011 to check for more recent publications. SELECTION CRITERIA: Randomized and quasi-randomized trials comparing the effect of using cold-water immersion after exercise with: passive intervention (rest/no intervention, contrast immersion, warm-water immersion, active recovery, compression, or a different duration/dosage of cold-water immersion. Primary outcomes were pain (muscle soreness or tenderness (pain on palpation, and subjective recovery (return to previous activities without signs or symptoms. DATA COLLECTION AND ANALYSIS: Three authors independently evaluated study quality and extracted data. Some of the data were obtained following author correspondence or extracted from graphs in the trial reports. Where possible, data were pooled using the fixed-effect model. MAIN RESULTS: Seventeen small trials were included, involving a total of 366 participants. Study quality was low. The temperature, duration and

  14. Spinal Muscular Atrophy

    Science.gov (United States)

    ... most often affected. Complications include scoliosis and joint contractures—chronic shortening of muscles or tendons around joints, ... of SMA include: Congenital SMA with arthrogryposis (persistent contracture of joints with fixed abnormal posture of the ...

  15. 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.

  16. 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.

  17. Impact of protein supplementation and exercise in preventing changes in gene expression profiling in woman muscles after long-term bedrest as revealed by microarray analysis.

    Science.gov (United States)

    Chopard, Angele; Lecunff, Martine; Danger, Richard; Teusan, Raluca; Jasmin, Bernard J.; Marini, Jean-Francois; Leger, Jean

    modifications of extracellular matrix and cytoskeletal components, were significant in SOL. Among the two recently described markers of atrophy, only MAFbx transcripts exhibited an increase in VL following 60 days of LTBR. While protein supplementation reduced the number of differentially-expressed genes by 40 and 25% for SOL and VL, respectively, the combined exercise regimen resulted in a marked beneficial and compensatory effect by decreasing the number of differentially-expressed mRNAs by more than 90% in both SOL and VL muscles. Together, these findings provide an overview of skeletal muscle impairment following prolonged disuse by identifying specific groups of genes related to muscle function, as well as metabolic and canonical signaling pathways. Furthermore, these results highlight the importance of regular exercise in the maintenance of both slow and fast muscle phenotypes. Finally, our approach will prove useful in designing and optimizing specific countermeasures aimed at counteracting muscle atrophy in a microgravity environment.

  18. 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 ...

  19. The inheritance of peripapillary atrophy

    NARCIS (Netherlands)

    Healey, Paul R.; Mitchell, Paul; Gilbert, Clare E.; Lee, Anne J.; Ge, Dongliang; Snieder, Harold; Spector, Timothy D.; Hammond, Christopher J.

    PURPOSE. To estimate the relative importance of genes and environment in peripapillary atrophy type beta (beta-PPA) in a classic twin study. METHODS. Female twin pairs (n = 506) aged 49 to 79 years were recruited from the St. Thomas' UK Adult Twin Registry. Peripapillary atrophy was identified from

  20. Morphologic and Biochemical Changes in Dogs After Portacaval Shunt Plus Bile Fistula or Ileal Bypass: Failure of Bile Fistula or Ileal Bypass to Prevent Hepatocyte Atrophy

    Science.gov (United States)

    Thompson, Jon S.; Porter, Kendrick A.; Hayashida, Nobuo; McNamara, Donald J.; Parker, Thomas S.; Russell, William J. I.; Francavilla, Antonio; Starzl, Thomas E.

    2010-01-01

    External biliary fistula (BF) or ileal bypass (IB) was performed in dogs at the time of or 2 weeks after portacaval shunt (PCS). The pathologic changes in the dog livers 2 to 4 weeks later were compared to those caused by PCS alone. Histopathologic differences between PCS alone vs. PCS plus BF or IB could not be found. Thus, the experiments did not confirm recent observations by others in rats that BF prevents or reverses the hepatic injury of PCS. As estimated by plasma mevalonic acid determinations, the increase in hepatic cholesterol synthesis that is characteristic after BF or IB was suppressed in animals with PCS. BF and IB reduced but did not eliminate the postprandial elevation in serum bile acid that occurs after PCS. The findings have possible relevance in planning the treatment of patients with familial hypercholesterolemia with the combined use of PCS and IB. PMID:6862371

  1. Myo/Nog cells: targets for preventing the accumulation of skeletal muscle-like cells in the human lens.

    Directory of Open Access Journals (Sweden)

    Jacquelyn Gerhart

    Full Text Available Posterior capsule opacification (PCO is a vision impairing condition that arises in some patients following cataract surgery. The fibrotic form of PCO is caused by myofibroblasts that may emerge in the lens years after surgery. In the chick embryo lens, myofibroblasts are derived from Myo/Nog cells that are identified by their expression of the skeletal muscle specific transcription factor MyoD, the bone morphogenetic protein inhibitor Noggin, and the epitope recognized by the G8 monoclonal antibody. The goal of this study was to test the hypothesis that depletion of Myo/Nog cells will prevent the accumulation of myofibroblasts in human lens tissue. Myo/Nog cells were present in anterior, equatorial and bow regions of the human lens, cornea and ciliary processes. In anterior lens tissue removed by capsulorhexis, Myo/Nog cells had synthesized myofibroblast and skeletal muscle proteins, including vimentin, MyoD and sarcomeric myosin. Alpha smooth muscle actin (α-SMA was detected in a subpopulation of Myo/Nog cells. Areas of the capsule denuded of epithelial cells were surrounded by Myo/Nog cells. Some of these cell free areas contained a wrinkle in the capsule. Depletion of Myo/Nog cells eliminated cells expressing skeletal muscle proteins in 5-day cultures but did not affect cells immunoreactive for beaded filament proteins that accumulate in differentiating lens epithelial cells. Transforming growth factor-betas 1 and 2 that mediate an epithelial-mesenchymal transition, did not induce the expression of skeletal muscle proteins in lens cells following Myo/Nog cell depletion. This study demonstrates that Myo/Nog cells in anterior lens tissue removed from cataract patients have undergone a partial differentiation to skeletal muscle. Myo/Nog cells appear to be the source of skeletal muscle-like cells in explants of human lens tissue. Targeting Myo/Nog cells with the G8 antibody during cataract surgery may reduce the incidence of PCO.

  2. Galectin-1 Protein Therapy Prevents Pathology and Improves Muscle Function in the mdx Mouse Model of Duchenne Muscular Dystrophy.

    Science.gov (United States)

    Van Ry, Pam M; Wuebbles, Ryan D; Key, Megan; Burkin, Dean J

    2015-08-01

    Duchenne muscular dystrophy (DMD) is a fatal neuromuscular disease caused by mutations in the dystrophin gene, leading to the loss of a critical component of the sarcolemmal dystrophin glycoprotein complex. Galectin-1 is a small 14 kDa protein normally found in skeletal muscle and has been shown to be a modifier of immune response, muscle repair, and apoptosis. Galectin-1 levels are elevated in the muscle of mouse and dog models of DMD. Together, these findings led us to hypothesize that Galectin-1 may serve as a modifier of disease progression in DMD. To test this hypothesis, recombinant mouse Galectin-1 was produced and used to treat myogenic cells and the mdx mouse model of DMD. Here we show that intramuscular and intraperitoneal injections of Galectin-1 into mdx mice prevented pathology and improved muscle function in skeletal muscle. These improvements were a result of enhanced sarcolemmal stability mediated by elevated utrophin and α7β1 integrin protein levels. Together our results demonstrate for the first time that Galectin-1 may serve as an exciting new protein therapeutic for the treatment of DMD.

  3. β3-adrenoceptor agonist prevents alterations of muscle diacylglycerol and adipose tissue phospholipids induced by a cafeteria diet

    Directory of Open Access Journals (Sweden)

    Darimont Christian

    2004-08-01

    Full Text Available Abstract Background Insulin resistance induced by a high fat diet has been associated with alterations in lipid content and composition in skeletal muscle and adipose tissue. Administration of β3-adrenoceptor (β3-AR agonists was recently reported to prevent insulin resistance induced by a high fat diet, such as the cafeteria diet. The objective of the present study was to determine whether a selective β3-AR agonist (ZD7114 could prevent alterations of the lipid profile of skeletal muscle and adipose tissue lipids induced by a cafeteria diet. Methods Male Sprague-Dawley rats fed a cafeteria diet were treated orally with either the β3-AR agonist ZD7114 (1 mg/kg per day or the vehicle for 60 days. Rats fed a chow diet were used as a reference group. In addition to the determination of body weight and insulin plasma level, lipid content and fatty acid composition in gastronemius and in epididymal adipose tissue were measured by gas-liquid chromatography, at the end of the study. Results In addition to higher body weights and plasma insulin concentrations, rats fed a cafeteria diet had greater triacylglycerol (TAG and diacylglycerol (DAG accumulation in skeletal muscle, contrary to animals fed a chow diet. As expected, ZD7114 treatment prevented the excessive weight gain and hyperinsulinemia induced by the cafeteria diet. Furthermore, in ZD7114 treated rats, intramyocellular DAG levels were lower and the proportion of polyunsaturated fatty acids, particularly arachidonic acid, in adipose tissue phospholipids was higher than in animals fed a cafeteria diet. Conclusions These results show that activation of the β3-AR was able to prevent lipid alterations in muscle and adipose tissue associated with insulin resistance induced by the cafeteria diet. These changes in intramyocellular DAG levels and adipose tissue PL composition may contribute to the improved insulin sensitivity associated with β3-AR activation.

  4. Overexpression of Catalase in Vascular Smooth Muscle Cells Prevents the Formation of Abdominal Aortic Aneurysms

    Science.gov (United States)

    Parastatidis, Ioannis; Weiss, Daiana; Joseph, Giji; Taylor, W Robert

    2013-01-01

    Objective Elevated levels of oxidative stress have been reported in abdominal aortic aneurysms (AAA), but which reactive oxygen species (ROS) promotes the development of AAA remains unclear. Here we investigate the effect of the hydrogen peroxide (H2O2) degrading enzyme catalase on the formation of AAA. Approach and Results AAA were induced with the application of calcium chloride (CaCl2) on mouse infrarenal aortas. The administration of PEG-catalase, but not saline, attenuated the loss of tunica media and protected against AAA formation (0.91±0.1 mm vs. 0.76±0.09 mm). Similarly, in a transgenic mouse model, catalase over-expression in the vascular smooth muscle cells (VSMC) preserved the thickness of tunica media and inhibited aortic dilatation by 50% (0.85±0.14 mm vs. 0.57±0.08 mm). Further studies showed that injury with CaCl2 decreased catalase expression and activity in the aortic wall. Pharmacologic administration or genetic over-expression of catalase restored catalase activity and subsequently decreased matrix metalloproteinase activity. In addition, a profound reduction in inflammatory markers and VSMC apoptosis was evident in aortas of catalase over-expressing mice. Interestingly, as opposed to infusion of PEG-catalase, chronic over-expression of catalase in VSMC did not alter the total aortic H2O2 levels. Conclusions The data suggest that a reduction in aortic wall catalase activity can predispose to AAA formation. Restoration of catalase activity in the vascular wall enhances aortic VSMC survival and prevents AAA formation primarily through modulation of matrix metalloproteinase activity. PMID:23950141

  5. 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

  6. 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.

  7. 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.

  8. Maternal creatine supplementation during pregnancy prevents acute and long-term deficits in skeletal muscle after birth asphyxia: a study of structure and function of hind limb muscle in the spiny mouse.

    Science.gov (United States)

    LaRosa, Domenic A; Ellery, Stacey J; Snow, Rod J; Walker, David W; Dickinson, Hayley

    2016-12-01

    Maternal antenatal creatine supplementation protects the brain, kidney, and diaphragm against the effects of birth asphyxia in the spiny mouse. In this study, we examined creatine's potential to prevent damage to axial skeletal muscles. Pregnant spiny mice were fed a control or creatine-supplemented diet from mid-pregnancy, and 1 d before term (39 d), fetuses were delivered by c-section with or without 7.5 min of birth asphyxia. At 24 h or 33 ± 2 d after birth, gastrocnemius muscles were obtained for ex-vivo study of twitch-tension, muscle fatigue, and structural and histochemical analysis. Birth asphyxia significantly reduced cross-sectional area of all muscle fiber types (P creatine treatment prevented all asphyxia-induced changes in the gastrocnemius, improved motor performance. This study demonstrates that creatine loading before birth protects the muscle from asphyxia-induced damage at birth.

  9. 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

  10. Overweight in elderly people induces impaired autophagy in skeletal muscle.

    Science.gov (United States)

    Potes, Yaiza; de Luxán-Delgado, Beatriz; Rodriguez-González, Susana; Guimarães, Marcela Rodrigues Moreira; Solano, Juan J; Fernández-Fernández, María; Bermúdez, Manuel; Boga, Jose A; Vega-Naredo, Ignacio; Coto-Montes, Ana

    2017-09-01

    Sarcopenia is the gradual loss of skeletal muscle mass, strength and quality associated with aging. Changes in body composition, especially in skeletal muscle and fat mass are crucial steps in the development of chronic diseases. We studied the effect of overweight on skeletal muscle tissue in elderly people without reaching obesity to prevent this extreme situation. Overweight induces a progressive protein breakdown reflected as a progressive withdrawal of anabolism against the promoted catabolic state leading to muscle wasting. Protein turnover is regulated by a network of signaling pathways. Muscle damage derived from overweight displayed by oxidative and endoplasmic reticulum (ER) stress induces inflammation and insulin resistance and forces the muscle to increase requirements from autophagy mechanisms. Our findings showed that failure of autophagy in the elderly deprives it to deal with the cell damage caused by overweight. This insufficiently efficient autophagy leads to an accumulation of p62 and NBR1, which are robust markers of protein aggregations. This impaired autophagy affects myogenesis activity. Depletion of myogenic regulatory factors (MRFs) without links to variations in myostatin levels in overweight patients suggest a possible reduction of satellite cells in muscle tissue, which contributes to declined muscle quality. This discovery has important implications that improve the understanding of aged-related atrophy caused by overweight and demonstrates how impaired autophagy is one of the main responsible mechanisms that aggravate muscle wasting. Therefore, autophagy could be an interesting target for therapeutic interventions in humans against muscle impairment diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. PPARβ/δ regulates glucocorticoid- and sepsis-induced FOXO1 activation and muscle wasting.

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    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.

  12. ROLE OF HAMSTRING MUSCLES IN KNEE JOINT STABILITY PROVIDING AND INJURY PREVENTION

    OpenAIRE

    Pontaga, Inese

    2016-01-01

    The aim of our investigation was to determine the ratio of maximal torque values and the torques in the certain positions of range of movements (ROM) between hamstring (H) and quadriceps femoris (Q) muscles at medium and high velocity of movement in concentric (CC) and eccentric (ECC) action of hamstring muscles. The knee muscles of 15 amateur female short and middle distance runners were tested by the dynamometer system in the isokinetic movements with the angular velocity of 90º/s and 240º...

  13. Vitamin D prevents lipid accumulation in murine muscle through regulation of PPARγ and perilipin-2 expression.

    Science.gov (United States)

    Li, Jiarong; Mihalcioiu, Milton; Li, Lifeng; Zakikhani, Mahvash; Camirand, Anne; Kremer, Richard

    2018-03-01

    Vitamin D plays an important role in regulation of skeletal muscle tone and contraction. Serum vitamin D status is linked to muscle power and force in adolescent girls, and vitamin D deficiency is associated with myopathies in children and poorer physical performance in the elderly. We previously reported that vitamin D deficiency is linked to a significant increase in muscle fatty infiltration in healthy young women, and studies in patients with neuromuscular disorders also associate muscle weakening and lipid content. In order to better understand the link between vitamin D status and skeletal muscle lipid metabolism, we compared the effect of a low (25IU/kg) or normal (1000IU/kg) vitamin D 3 diet on muscle fat in female FVB mice maintained in a room without UVB lighting to minimize endogenous vitamin D production. Animals on low vitamin D diet displayed lower circulating 25(OH)D levels and a dramatic increase (287±52% compared to normal diet, p<0.0001) in lipid deposition in skeletal muscle accompanied by muscle fiber disorganization. Lipid droplet staining increased by 242±23% (p<0.0001) in low vitamin D diet, and lipid droplet coat protein perilipin-2 and nuclear receptor transcription factor PPARγ expression levels were increased compared to mice fed the normal vitamin D diet: average staining for PLIN2: 0.22±0.08 (25IU/kg diet) vs 0.10±0.02 (1000IU/kg). Average staining for PPARγ: 0.24±0.06 (25IU/kg diet) vs 0.07±0.04 (1000IU/kg) p<0.0001. Tissue mass spectrometry imaging revealed major differences in muscle phospholipids profile depending on diet. In vitro, 1,25(OH) 2 D 3 treatment of 3T3-L1 pre-adipocytes inhibited appearance of lipid droplets by 79±9.3%, and caused a 80±10% and 25±8% (p=0.001) reduction in PPARγ and perilipin-2 mRNA levels (by qPCR) compared to control cells. In summary, we report here the first in vivo model illustrating the important structural muscle fiber disorganization and fat accumulation inside and outside muscle

  14. Voluntary Exercise Prevents Cisplatin-Induced Muscle Wasting during Chemotherapy in Mice

    DEFF Research Database (Denmark)

    Hojman, Pernille; Fjelbye, Jonas; Zerahn, Bo

    2014-01-01

    , food intake as well as muscle mass, strength and signalling. Mice were treated weekly with 4 mg/kg cisplatin or saline for 6 weeks, and randomized to voluntary wheel running or not. Cisplatin treatment induced loss of body weight (29.8%, P ... as anorexia, impaired muscle strength (22.5% decrease, P wheel running during treatment attenuated body weight...... loss by 50% (P wheel running, nor was glucose tolerance improved. Exercise...

  15. Resistance Training Prevents Muscle Loss Induced by Caloric Restriction in Obese Elderly Individuals: A Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Amanda V. Sardeli

    2018-03-01

    Full Text Available It remains unclear as to what extent resistance training (RT can attenuate muscle loss during caloric restriction (CR interventions in humans. The objective here is to address if RT could attenuate muscle loss induced by CR in obese elderly individuals, through summarized effects of previous studies. Databases MEDLINE, Embase and Web of Science were used to perform a systematic search between July and August 2017. Were included in the review randomized clinical trials (RCT comparing the effects of CR with (CRRT or without RT on lean body mass (LBM, fat body mass (FBM, and total body mass (BM, measured by dual-energy X-ray absorptiometry, on obese elderly individuals. The six RCTs included in the review applied RT three times per week, for 12 to 24 weeks, and most CR interventions followed diets of 55% carbohydrate, 15% protein, and 30% fat. RT reduced 93.5% of CR-induced LBM loss (0.819 kg [0.364 to 1.273], with similar reduction in FBM and BM, compared with CR. Furthermore, to address muscle quality, the change in strength/LBM ratio tended to be different (p = 0.07 following CRRT (20.9 ± 23.1% and CR interventions (−7.5 ± 9.9%. Our conclusion is that CRRT is able to prevent almost 100% of CR-induced muscle loss, while resulting in FBM and BM reductions that do not significantly differ from CR.

  16. 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.

  17. Estimulação elétrica neuromuscular de média freqüência (russa em cães com atrofia muscular induzida Medium frequency neuromuscular electrical stimulation (russian in dogs with induced muscle atrophy

    Directory of Open Access Journals (Sweden)

    Charles Pelizzari

    2008-06-01

    Full Text Available A estimulação elétrica neuromuscular (EENM de média freqüência (Russa ou de Kotz pode ser empregada para a recuperação de massa muscular em animais apresentando atrofia muscular por desuso. Assim, o objetivo deste trabalho foi empregar a EENM de média freqüência no quadríceps femoral de cães com atrofia muscular induzida, avaliando-se a ocorrência de ganho de massa. Foram utilizados oito cães em dois grupos denominados de GI ou controle e de GII ou tratado. Para a indução da atrofia muscular, a articulação fêmoro-tíbio-patelar esquerda foi imobilizada por 30 dias. Após 48 horas da remoção, foi realizada a EENM nos cães do grupo II, três vezes por semana, com intervalo de 48 horas cada sessão, pelo período de 60 dias. Foram avaliadas a mensuração da perimetria da coxa, da goniometria do joelho, as enzimas creatina-quinase (CK e morfometria das fibras musculares em cortes transversais do músculo vasto lateral, colhido mediante a biópsia muscular. A EENM foi empregada no músculo quadríceps femoral numa freqüência de 2.500Hz, largura de pulso de 50% e relação de tempo on/off de 1:2. Não houve diferença significativa quanto aos valores de perimetria da coxa e a atividade da enzima CK entre os grupos I e II. Na goniometria, houve diminuição significativa (PThe medium frequency neuromuscular electrical stimulation (NMES (Russa or Kotz is designed for recuperation of muscle mass in dogs with muscular atrophy in disuse. This study aims to utilize medium frequency NMES on the femoral quadriceps of dogs with induced muscular atrophy and evaluate the occurrence of gain in mass. Eight dogs in two groups denominated GI, or control, and GII, or treated were used. For the induction of muscular atrophy, the left femoral-tibial-patellar joint was immobilized for 30 days. NMES treatment began 48 hours after the removal of the immobilization device on dogs from group II and was carried out three times per week, with an

  18. Neuromuscular electrical stimulation for preventing skeletal-muscle weakness and wasting in critically ill patients

    DEFF Research Database (Denmark)

    Maffiuletti, Nicola A.; Roig, Marc; Karatzanos, Eleftherios

    2013-01-01

    ill patients, in comparison with usual care. Methods: We searched PubMed, CENTRAL, CINAHL, Web of Science, and PEDro to identify randomized controlled trials exploring the effect of NMES in critically ill patients, which had a well-defined NMES protocol, provided outcomes related to skeletal......-muscle strength and/or mass, and for which full text was available. Two independent reviewers extracted data on muscle-related outcomes (strength and mass), and participant and intervention characteristics, and assessed the methodological quality of the studies. Owing to the lack of means and standard deviations...... yielded 8 eligible studies involving 172 patients. The methodological quality of the studies was moderate to high. Five studies reported an increase in strength or better preservation of strength with NMES, with one study having a large effect size. Two studies found better preservation of muscle mass...

  19. 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...

  20. Multiple System Atrophy

    Science.gov (United States)

    ... tissue of patients with MSA is a potent inducer of alpha-synuclein clumping when injected into the ... Through Research Know Your Brain Preventing Stroke Understanding Sleep The Life and Death of a Neuron Genes ...

  1. Suppression of Eosinophil Integrins Prevents Remodeling of Airway Smooth Muscle in Asthma

    NARCIS (Netherlands)

    Januskevicius, Andrius; Gosens, Reinoud; Sakalauskas, Raimundas; Vaitkiene, Simona; Janulaityte, Ieva; Halayko, Andrew J; Hoppenot, Deimante; Malakauskas, Kestutis

    2017-01-01

    Background: Airway smooth muscle (ASM) remodeling is an important component of the structural changes to airways seen in asthma. Eosinophils are the prominent inflammatory cells in asthma, and there is some evidence that they contribute to ASM remodeling via released mediators and direct contact

  2. Voluntary exercise prevents cisplatin-induced muscle wasting during chemotherapy in mice

    DEFF Research Database (Denmark)

    Hojman, Pernille; Fjelbye, Jonas; Zerahn, Bo

    2014-01-01

    Loss of muscle mass related to anti-cancer therapy is a major concern in cancer patients, being associated with important clinical endpoints including survival, treatment toxicity and patient-related outcomes. We investigated effects of voluntary exercise during cisplatin treatment on body weight......% (PExercise training may...

  3. Drosophila UNC-45 prevents heat-induced aggregation of skeletal muscle myosin and facilitates refolding of citrate synthase

    Energy Technology Data Exchange (ETDEWEB)

    Melkani, Girish C.; Lee, Chi F.; Cammarato, Anthony [Department of Biology and the Molecular Biology Institute, San Diego State University, San Diego, CA 92182-4614 (United States); Bernstein, Sanford I., E-mail: sbernst@sciences.sdsu.edu [Department of Biology and the Molecular Biology Institute, San Diego State University, San Diego, CA 92182-4614 (United States)

    2010-05-28

    UNC-45 belongs to the UCS (UNC-45, CRO1, She4p) domain protein family, whose members interact with various classes of myosin. Here we provide structural and biochemical evidence that Escherichia coli-expressed Drosophila UNC-45 (DUNC-45) maintains the integrity of several substrates during heat-induced stress in vitro. DUNC-45 displays chaperone function in suppressing aggregation of the muscle myosin heavy meromyosin fragment, the myosin S-1 motor domain, {alpha}-lactalbumin and citrate synthase. Biochemical evidence is supported by electron microscopy, which reveals the first structural evidence that DUNC-45 prevents inter- or intra-molecular aggregates of skeletal muscle heavy meromyosin caused by elevated temperatures. We also demonstrate for the first time that UNC-45 is able to refold a denatured substrate, urea-unfolded citrate synthase. Overall, this in vitro study provides insight into the fate of muscle myosin under stress conditions and suggests that UNC-45 protects and maintains the contractile machinery during in vivo stress.

  4. TGF-β Small Molecule Inhibitor SB431542 Reduces Rotator Cuff Muscle Fibrosis and Fatty Infiltration By Promoting Fibro/Adipogenic Progenitor Apoptosis.

    Directory of Open Access Journals (Sweden)

    Michael R Davies

    Full Text Available Rotator cuff tears represent a large burden of muscle-tendon injuries in our aging population. While small tears can be repaired surgically with good outcomes, critical size tears are marked by muscle atrophy, fibrosis, and fatty infiltration, which can lead to failed repair, frequent re-injury, and chronic disability. Previous animal studies have indicated that Transforming Growth Factor-β (TGF-β signaling may play an important role in the development of these muscle pathologies after injury. Here, we demonstrated that inhibition of TGF-β1 signaling with the small molecule inhibitor SB431542 in a mouse model of massive rotator cuff tear results in decreased fibrosis, fatty infiltration, and muscle weight loss. These observed phenotypic changes were accompanied by decreased fibrotic, adipogenic, and atrophy-related gene expression in the injured muscle of mice treated with SB431542. We further demonstrated that treatment with SB431542 reduces the number of fibro/adipogenic progenitor (FAP cells-an important cellular origin of rotator cuff muscle fibrosis and fatty infiltration, in injured muscle by promoting apoptosis of FAPs. Together, these data indicate that the TGF-β pathway is a critical regulator of the degenerative muscle changes seen after massive rotator cuff tears. TGF-β promotes rotator cuff muscle fibrosis and fatty infiltration by preventing FAP apoptosis. TGF-β regulated FAP apoptosis may serve as an important target pathway in the future development of novel therapeutics to improve muscle outcomes following rotator cuff tear.

  5. 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.

  6.  Age-related changes of skeletal muscles: physiology, pathology and regeneration

    Directory of Open Access Journals (Sweden)

    Aleksandra Ławniczak

    2012-06-01

    Full Text Available  This review provides a short presentation of the aging-related changes of human skeletal muscles. The aging process is associated with the loss of skeletal muscle mass (sarcopenia and strength. This results from fibre atrophy and apoptosis, decreased regeneration capacity, mitochondrial dysfunction, gradual reduction of the number of spinal cord motor neurons, and local and systemic metabolic and hormonal alterations. The latter involve age-related decrease of the expression and activity of some mitochondrial and cytoplasmic enzymes, triacylglycerols and lipofuscin accumulation inside muscle fibres, increased proteolytic activity, insulin resistance and decreased serum growth hormone and IGF-1 concentrations. Aging of the skeletal muscles is also associated with a decreased number of satellite cells and their proliferative activity. The age-related reduction of skeletal muscle mass and function may be partially prevented by dietary restriction and systematic physical exercises.

  7. 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.

  8. Electromechanical delay of abdominal muscles is modified by low back pain prevention exercise.

    Science.gov (United States)

    Szpala, Agnieszka; Rutkowska-Kucharska, Alicja; Drapala, Jaroslaw

    2014-01-01

    The objective of the research was to assess the effect of a 4-week-long training program on selected parameters: electromechanical delay (EMD) and amplitude of electromyographic signal (EMG). Fourteen female students of the University School of Physical Education participated in the study. Torques and surface electromyography were evaluated under static conditions. Surface electrodes were glued to both sides of the rectus abdominis (RA), external oblique (EO), and erector spinae (ES) muscles. The 4-week-long program was aimed at strengthening the abdominal muscles and resulted in increased EMD during maximum torque production by flexors of the trunk, increased amplitudes of the signals of the erector spinae ( p = 0.005), and increased EMG amplitude asymmetry of the lower ( p = 0.013) and upper part ( p = 0.006) of the rectus abdominis muscle. In a training program composed of a large number of repetitions of strength exercises, in which the training person uses their own weight as the load (like in exercises such as curl-ups), the process of recruitment of motor units is similar to that found during fatiguing exercises and plyometric training.

  9. 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.

  10. Chronic exercise preserves lean muscle mass in masters athletes.

    Science.gov (United States)

    Wroblewski, Andrew P; Amati, Francesca; Smiley, Mark A; Goodpaster, Bret; Wright, Vonda

    2011-09-01

    Aging is commonly associated with a loss of muscle mass and strength, resulting in falls, functional decline, and the subjective feeling of weakness. Exercise modulates the morbidities of muscle aging. Most studies, however, have examined muscle-loss changes in sedentary aging adults. This leaves the question of whether the changes that are commonly associated with muscle aging reflect the true physiology of muscle aging or whether they reflect disuse atrophy. This study evaluated whether high levels of chronic exercise prevents the loss of lean muscle mass and strength experienced in sedentary aging adults. A cross-section of 40 high-level recreational athletes ("masters athletes") who were aged 40 to 81 years and trained 4 to 5 times per week underwent tests of health/activity, body composition, quadriceps peak torque (PT), and magnetic resonance imaging of bilateral quadriceps. Mid-thigh muscle area, quadriceps area (QA), subcutaneous adipose tissue, and intramuscular adipose tissue were quantified in magnetic resonance imaging using medical image processing, analysis, and visualization software. One-way analysis of variance was used to examine age group differences. Relationships were evaluated using Spearman correlations. Mid-thigh muscle area (P = 0.31) and lean mass (P = 0.15) did not increase with age and were significantly related to retention of mid-thigh muscle area (P lean mass (P = 0.4) and PT. This study contradicts the common observation that muscle mass and strength decline as a function of aging alone. Instead, these declines may signal the effect of chronic disuse rather than muscle aging. Evaluation of masters athletes removes disuse as a confounding variable in the study of lower-extremity function and loss of lean muscle mass. This maintenance of muscle mass and strength may decrease or eliminate the falls, functional decline, and loss of independence that are commonly seen in aging adults.

  11. Preventive and Regenerative Foam Rolling are Equally Effective in Reducing Fatigue-Related Impairments of Muscle Function following Exercise

    Directory of Open Access Journals (Sweden)

    Johannes Fleckenstein, Jan Wilke, Lutz Vogt, Winfried Banzer

    2017-12-01

    Full Text Available Objectives of the study were to compare the effects of a single bout of preventive or regenerative foam rolling (FR on exercise-induced neuromuscular exhaustion. Single-centre randomised-controlled study was designed. Forty-five healthy adults (22 female; 25±2 yrs were allocated to three groups: 1 FR of the lower limb muscles prior to induction of fatigue, 2 FR after induction of fatigue, 3 no-treatment control. Neuromuscular exhaustion was provoked using a standardized and validated functional agility short-term fatigue protocol. Main outcome measure was the maximal isometric voluntary force of the knee extensors (MIVF. Secondary outcomes included pain and reactive strength (RSI. Preventive (-16% and regenerative FR (-12% resulted in a decreased loss in MIVF compared to control (-21%; p 0.8, p < 0.1. Differences over time (p < 0.001 between groups regarding pain and RSI did not turn out to be clinically meaningful. A single bout of foam rolling reduces neuromuscular exhaustion with reference to maximal force production. Regenerative rather than preventive foam rolling seems sufficient to prevent further fatigue.

  12. 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.

  13. Pelvic floor muscle training for prevention and treatment of urinary and faecal incontinence in antenatal and postnatal women.

    Science.gov (United States)

    Boyle, Rhianon; Hay-Smith, E Jean C; Cody, June D; Mørkved, Siv

    2012-10-17

    About a third of women have urinary incontinence and up to a 10th have faecal incontinence after childbirth. Pelvic floor muscle training is commonly recommended during pregnancy and after birth both for prevention and the treatment of incontinence. To determine the effect of pelvic floor muscle training compared to usual antenatal and postnatal care on incontinence. We searched the Cochrane Incontinence Group Specialised Register, which includes searches of CENTRAL, MEDLINE, MEDLINE in Process and handsearching (searched 7 February 2012) and the references of relevant articles. Randomised or quasi-randomised trials in pregnant or postnatal women. One arm of the trial needed to include pelvic floor muscle training (PFMT). Another arm was either no PFMT or usual antenatal or postnatal care. Trials were independently assessed for eligibility and methodological quality. Data were extracted then cross checked. Disagreements were resolved by discussion. Data were processed as described in the Cochrane Handbook for Systematic Reviews of Interventions. Three different populations of women were considered separately, women dry at randomisation (prevention); women wet at randomisation (treatment); and a mixed population of women who might be one or the other (prevention or treatment). Trials were further divided into those which started during pregnancy (antenatal); and those started after delivery (postnatal). Twenty-two trials involving 8485 women (4231 PFMT, 4254 controls) met the inclusion criteria and contributed to the analysis.Pregnant women without prior urinary incontinence (prevention) who were randomised to intensive antenatal PFMT were less likely than women randomised to no PFMT or usual antenatal care to report urinary incontinence up to six months after delivery (about 30% less; risk ratio (RR) 0.71, 95% CI 0.54 to 0.95, combined result of 5 trials).Postnatal women with persistent urinary incontinence (treatment) three months after delivery and who received

  14. Genetics Home Reference: spinal muscular atrophy

    Science.gov (United States)

    ... difficulty breathing. Children with this type often have joint deformities (contractures) that impair movement. In severe cases, ... Proximal spinal muscular atrophy Washington University, St. Louis: Neuromuscular Disease Center: Spinal Muscular Atrophy Patient Support and ...

  15. Hemifacial atrophy treated with autologous fat transplantation

    Directory of Open Access Journals (Sweden)

    Gandhi Vijay

    2005-01-01

    Full Text Available A 23-year-old male developed right hemifacial atrophy following marphea profunda. Facial asymmetry due to residual atrophy was treated with autologous fat harvested from buttocks with marked cosmetic improvement.

  16. Does peroperative external pneumatic leg muscle compression prevent post-operative venous thrombosis in neurosurgery?

    Science.gov (United States)

    Bynke, O; Hillman, J; Lassvik, C

    1987-01-01

    Post-operative deep venous thrombosis (DVT) is a frequent and potentially life-threatening complication in neurosurgery. In this field of surgery, with its special demands for exact haemostasis, prophylaxis against deep venous thrombosis with anticoagulant drugs has been utilized only reluctantly. Postoperative pneumatic muscle compression (EPC) has been shown to be effective, although there are several practical considerations involved with this method which limit its clinical applicability. In the present study per-operative EPC was evaluated and was found to provide good protection against DVT in patients with increased risk from this complication. This method has the advantage of being effective, safe, inexpensive and readily practicable.

  17. 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.

  18. Aspectos clínicos e concentração sérica da creatina-quinase e lactato-desidrogenase em cães submetidos à fisioterapia após atrofia muscular induzida Clinical aspects and serum concentration creatina kinase and lactate dehydrogenase in dogs submitted to physiotherapy after induced muscle atrophy

    Directory of Open Access Journals (Sweden)

    Soraia Figueiredo de Souza

    2011-07-01

    Full Text Available Avaliou-se a resposta de diferentes protocolos fisioterapêuticos em cães após a indução de atrofia muscular por meio da imobilização do joelho por 30 dias. Os grupos foram denominados grupo C ou controle, grupo E (massagem, movimentação passiva e eletroterapia, grupo H (massagem, movimentação passiva e hidroterapia em esteira aquática e grupo EH (massagem, movimentação passiva, eletroterapia e hidroterapia em esteira aquática. Foram mensurados os graus de claudicação, arco do movimento, circunferência da coxa e a variação sérica das enzimas creatina-quinase e lactato-desidrogenase. De acordo com os resultados encontrados, foi possível concluir que as modalidades terapêuticas de massagem, movimentação passiva da articulação, estimulação elétrica neuromuscular e hidroterapia por caminhada em esteira aquática aceleram a recuperação clínica em cães com atrofia muscular induzida.The response of different physiotherapeutic treatment protocols was evaluated in dogs after muscle atrophy induced by joint immobilization for 30 days. Groups were named C group or control, E group (massage, passive range of motion and neuromuscular electrical stimulation, H group (massage, passive range of motion and aquatic therapy in underwater treadmill and EH group (massage, passive range of motion, neuromuscular electrical stimulation and aquatic therapy in underwater treadmill. It was measured the degree of lameness, range motion, thigh circumference and range of serum creatine kinase (CK and lactate dehydrogenase (LDH. According to the results, it was possible to conclude that associated therapeutics modalities such as massage, passive range of motion of the joint, neuromuscular electrical stimulation and aquatic therapy by walking on underwater treadmill accelerate clinical recovery in dogs with induced muscle atrophy.

  19. 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.

  20. Analysis of the Hamstring Muscle Activation During two Injury Prevention Exercises

    Science.gov (United States)

    Monajati, Alireza; Larumbe-Zabala, Eneko; Goss-Sampson, Mark

    2017-01-01

    Abstract The aim of this study was to perform an electromyographic and kinetic comparison of two commonly used hamstring eccentric strengthening exercises: Nordic Curl and Ball Leg Curl. After determining the maximum isometric voluntary contraction of the knee flexors, ten female athletes performed 3 repetitions of both the Nordic Curl and Ball Leg Curl, while knee angular displacement and electromyografic activity of the biceps femoris and semitendinosus were monitored. No significant differences were found between biceps femoris and semitendinosus activation in both the Nordic Curl and Ball Leg Curl. However, comparisons between exercises revealed higher activation of both the biceps femoris (74.8 ± 20 vs 50.3 ± 25.7%, p = 0.03 d = 0.53) and semitendinosus (78.3 ± 27.5 vs 44.3 ± 26.6%, p = 0.012, d = 0.63) at the closest knee angles in the Nordic Curl vs Ball Leg Curl, respectively. Hamstring muscles activation during the Nordic Curl increased, remained high (>70%) between 60 to 40° of the knee angle and then decreased to 27% of the maximal isometric voluntary contraction at the end of movement. Overall, the biceps femoris and semitendinosus showed similar patterns of activation. In conclusion, even though the hamstring muscle activation at open knee positions was similar between exercises, the Nordic Curl elicited a higher hamstring activity compared to the Ball Leg Curl. PMID:29339983

  1. 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.

  2. Whole-body cryotherapy (extreme cold air exposure) for preventing and treating muscle soreness after exercise in adults.

    Science.gov (United States)

    Costello, Joseph T; Baker, Philip R A; Minett, Geoffrey M; Bieuzen, Francois; Stewart, Ian B; Bleakley, Chris

    2015-09-18

    Recovery strategies are often used with the intention of preventing or minimising muscle soreness after exercise. Whole-body cryotherapy, which involves a single or repeated exposure(s) to extremely cold dry air (below -100 °C) in a specialised chamber or cabin for two to four minutes per exposure, is currently being advocated as an effective intervention to reduce muscle soreness after exercise. To assess the effects (benefits and harms) of whole-body cryotherapy (extreme cold air exposure) for preventing and treating muscle soreness after exercise in adults. We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register, the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, the British Nursing Index and the Physiotherapy Evidence Database. We also searched the reference lists of articles, trial registers and conference proceedings, handsearched journals and contacted experts.The searches were run in August 2015. We aimed to include randomised and quasi-randomised trials that compared the use of whole-body cryotherapy (WBC) versus a passive or control intervention (rest, no treatment or placebo treatment) or active interventions including cold or contrast water immersion, active recovery and infrared therapy for preventing or treating muscle soreness after exercise in adults. We also aimed to include randomised trials that compared different durations or dosages of WBC. Our prespecified primary outcomes were muscle soreness, subjective recovery (e.g. tiredness, well-being) and adverse effects. Two review authors independently screened search results, selected studies, assessed risk of bias and extracted and cross-checked data. Where appropriate, we pooled results of comparable trials. The random-effects model was used for pooling where there was substantial heterogeneity. We assessed the quality of the evidence using GRADE. Four laboratory-based randomised controlled trials were included. These reported results for 64

  3. Functional recovery of denervated skeletal muscle with sensory or mixed nerve protection: a pilot study.

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    Qing Tian Li

    Full Text Available Functional recovery is usually poor following peripheral nerve injury when reinnervation is delayed. Early innervation by sensory nerve has been indicated to prevent atrophy of the denervated muscle. It is hypothesized that early protection with sensory axons is adequate to improve functional recovery of skeletal muscle following prolonged denervation of mixed nerve injury. In this study, four groups of rats received surgical denervation of the tibial nerve. The proximal and distal stumps of the tibial nerve were ligated in all animals except for those in the immediate repair group. The experimental groups underwent denervation with nerve protection of peroneal nerve (mixed protection or sural nerve (sensory protection. The experimental and unprotected groups had a stage II surgery in which the trimmed proximal and distal tibial nerve stumps were sutured together. After 3 months of recovery, electrophysiological, histological and morphometric parameters were assessed. It was detected that the significant muscle atrophy and a good preserved structure of the muscle were observed in the unprotected and protective experimental groups, respectively. Significantly fewer numbers of regenerated myelinated axons were observed in the sensory-protected group. Enhanced recovery in the mixed protection group was indicated by the results of the muscle contraction force tests, regenerated myelinated fiber, and the results of the histological analysis. Our results suggest that early axons protection by mixed nerve may complement sensory axons which are required for promoting functional recovery of the denervated muscle natively innervated by mixed nerve.

  4. Isokinetic eccentric resistance training prevents loss in mechanical muscle function after running

    DEFF Research Database (Denmark)

    Oliveira, Anderson S. C.; Caputo, Fabrizio; Aagaard, Per

    2013-01-01

    session, subjects performed treadmill running (~35 min) and the previously mentioned measurements were repeated immediately after running. Subsequently, subjects were randomized to training (n = 12) consisting of 24 sessions of maximal IERT knee extensors actions at 180° s(-1), or served as controls (n...... damages. However, IERT may not avoid reductions in explosive muscle actions. In turn, this may allow more intense training sessions to be performed, facilitating the adaptive response to running training.......The aim of the study was to verify whether 8 weeks of resistance training employing maximal isokinetic eccentric (IERT) knee extensor actions would reduce the acute force loss observed after high-intensity treadmill running exercise. It was hypothesized that specific IERT would induce protective...

  5. Gentiana lutea exerts anti-atherosclerotic effects by preventing endothelial inflammation and smooth muscle cell migration.

    Science.gov (United States)

    Kesavan, R; Chandel, S; Upadhyay, S; Bendre, R; Ganugula, R; Potunuru, U R; Giri, H; Sahu, G; Kumar, P Uday; Reddy, G Bhanuprakash; Joksic, G; Bera, A K; Dixit, Madhulika

    2016-04-01

    Studies suggest that Gentiana lutea (GL), and its component isovitexin, may exhibit anti-atherosclerotic properties. In this study we sought to investigate the protective mechanism of GL aqueous root extract and isovitexin on endothelial inflammation, smooth muscle cell migation, and on the onset and progression of atherosclerosis in streptozotocin (STZ)-induced diabetic rats. Our results show that both GL extract and isovitexin, block leukocyte adhesion and generation of reactive oxygen species in human umbilical vein endothelial cells (HUVECs) and rat aortic smooth muscle cells (RASMCs), following TNF-alpha and platelet derived growth factor-BB (PDGF-BB) challenges respectively. Both the extract and isovitexin blocked TNF-α induced expression of ICAM-1 and VCAM-1 in HUVECs. PDGF-BB induced migration of RASMCs and phospholipase C-γ activation, were also abrogated by GL extract and isovitexin. Fura-2 based ratiometric measurements demonstrated that, both the extact, and isovitexin, inhibit PDGF-BB mediated intracellular calcium rise in RASMCs. Supplementation of regular diet with 2% GL root powder for STZ rats, reduced total cholesterol in blood. Oil Red O staining demonstrated decreased lipid accumulation in aortic wall of diabetic animals upon treatment with GL. Medial thickness and deposition of collagen in the aortic segment of diabetic rats were also reduced upon supplementation. Immunohistochemistry demonstrated reduced expression of vascular cell adhesion molecule-1 (VCAM-1), inducible nitric oxide synthase (iNOS), and vascular endothelial cadherin (VE-cadherin) in aortic segments of diabetic rats following GL treatment. Thus, our results support that GL root extract/powder and isovitexin exhibit anti-atherosclerotic activities. Copyright © 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University

  6. Botulinum toxin injection causes hyper-reflexia and increased muscle stiffness of the triceps surae muscle in the rat.

    Science.gov (United States)

    Pingel, Jessica; Wienecke, Jacob; Lorentzen, Jakob; Nielsen, Jens Bo

    2016-12-01

    Botulinum toxin is used with the intention of diminishing spasticity and reducing the risk of development of contractures. Here, we investigated changes in muscle stiffness caused by reflex activity or elastic muscle properties following botulinum toxin injection in the triceps surae muscle in rats. Forty-four rats received injection of botulinum toxin in the left triceps surae muscle. Control measurements were performed on the noninjected contralateral side in all rats. Acute experiments were performed, 1, 2, 4, and 8 wk following injection. The triceps surae muscle was dissected free, and the Achilles tendon was cut and attached to a muscle puller. The resistance of the muscle to stretches of different amplitudes and velocities was systematically investigated. Reflex-mediated torque was normalized to the maximal muscle force evoked by supramaximal stimulation of the tibial nerve. Botulinum toxin injection caused severe atrophy of the triceps surae muscle at all time points. The force generated by stretch reflex activity was also strongly diminished but not to the same extent as the maximal muscle force at 2 and 4 wk, signifying a relative reflex hyperexcitability. Passive muscle stiffness was unaltered at 1 wk but increased at 2, 4, and 8 wk (P botulinum toxin causes a relative increase in reflex stiffness, which is likely caused by compensatory neuroplastic changes. The stiffness of elastic elements in the muscles also increased. The data are not consistent with the ideas that botulinum toxin is an efficient antispastic medication or that it may prevent development of contractures. Copyright © 2016 the American Physiological Society.

  7. The cell nuclei of skeletal muscle cells are transcriptionally active in hibernating edible dormice

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    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

  8. 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.

  9. Serum IgE Induced Airway Smooth Muscle Cell Remodeling Is Independent of Allergens and Is Prevented by Omalizumab

    Science.gov (United States)

    Roth, Michael; Zhao, Feng; Zhong, Jun; Lardinois, Didier; Tamm, Michael

    2015-01-01

    Background Airway wall remodeling in allergic asthma is reduced after treatment with humanized anti-IgE-antibodies. We reported earlier that purified IgE, without the presence of allergens, is sufficient to induce airway wall remodeling due to airway smooth muscle cell (ASMC) activity deposing extracellular matrix. Objective We postulate that IgE contained in serum of allergic asthma patients, in the absence of allergens, stimulates ASMC remodeling activities and can be prevented by anti-IgE antibodies. Methods Isolated human ASMC were exposed to serum obtained from: (i) healthy controls, or patients with (ii) allergic asthma, (iii) non-allergic asthma, and (iv) atopic non-asthma patients. Proliferation and the deposition of collagens and fibronectin were determined after 3 and 5 days. Results Serum from patients with allergies significantly stimulated: (i) ASMC proliferation, (ii) deposition of collagen type-I (48 hours) and (iii) of fibronectin (24 hours). One hour pre-incubation with Omalizumab prevented these three effects of allergic serum, but had no significant effect on serum from healthy donors or non-allergic asthma patients. Interestingly, the addition of allergens did not further increase any of the IgE effects. Conclusion and Clinical Relevance Our data provides experimental evidence that the beneficial effect of Omalizumab on airway wall remodeling and improved lung function may be due to its direct action on IgE bound ASMC. PMID:26332463

  10. Serum IgE Induced Airway Smooth Muscle Cell Remodeling Is Independent of Allergens and Is Prevented by Omalizumab.

    Directory of Open Access Journals (Sweden)

    Michael Roth

    Full Text Available Airway wall remodeling in allergic asthma is reduced after treatment with humanized anti-IgE-antibodies. We reported earlier that purified IgE, without the presence of allergens, is sufficient to induce airway wall remodeling due to airway smooth muscle cell (ASMC activity deposing extracellular matrix.We postulate that IgE contained in serum of allergic asthma patients, in the absence of allergens, stimulates ASMC remodeling activities and can be prevented by anti-IgE antibodies.Isolated human ASMC were exposed to serum obtained from: (i healthy controls, or patients with (ii allergic asthma, (iii non-allergic asthma, and (iv atopic non-asthma patients. Proliferation and the deposition of collagens and fibronectin were determined after 3 and 5 days.Serum from patients with allergies significantly stimulated: (i ASMC proliferation, (ii deposition of collagen type-I (48 hours and (iii of fibronectin (24 hours. One hour pre-incubation with Omalizumab prevented these three effects of allergic serum, but had no significant effect on serum from healthy donors or non-allergic asthma patients. Interestingly, the addition of allergens did not further increase any of the IgE effects.Our data provides experimental evidence that the beneficial effect of Omalizumab on airway wall remodeling and improved lung function may be due to its direct action on IgE bound ASMC.

  11. PGC-1alpha is required for training-induced prevention of age-associated decline in mitochondrial enzymes in mouse skeletal muscle

    DEFF Research Database (Denmark)

    Leick, Lotte; Lyngby, Stine Secher; Wojtaszewski, Jørgen

    2010-01-01

    The aim of the present study was to test the hypothesis that exercise training prevents an age-associated decline in skeletal muscle mitochondrial enzymes through a PGC-1alpha dependent mechanism. Whole body PGC-1alpha knock-out (KO) and littermate wildtype (WT) mice were submitted to long term...

  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. PDZK1 prevents neointima formation via suppression of breakpoint cluster region kinase in vascular smooth muscle.

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    Wan Ru Lee

    Full Text Available Scavenger receptor class B, type I (SR-BI and its adaptor protein PDZK1 mediate responses to HDL cholesterol in endothelium. Whether the receptor-adaptor protein tandem serves functions in other vascular cell types is unknown. The current work determined the roles of SR-BI and PDZK1 in vascular smooth muscle (VSM. To evaluate possible VSM functions of SR-BI and PDZK1 in vivo, neointima formation was assessed 21 days post-ligation in the carotid arteries of wild-type, SR-BI-/- or PDZK1-/- mice. Whereas neointima development was negligible in wild-type and SR-BI-/-, there was marked neointima formation in PDZK1-/- mice. PDZK1 expression was demonstrated in primary mouse VSM cells, and compared to wild-type cells, PDZK1-/- VSM displayed exaggerated proliferation and migration in response to platelet derived growth factor (PDGF. Tandem affinity purification-mass spectrometry revealed that PDZK1 interacts with breakpoint cluster region kinase (Bcr, which contains a C-terminal PDZ binding sequence and is known to enhance responses to PDGF in VSM. PDZK1 interaction with Bcr in VSM was demonstrated by pull-down and by coimmunoprecipitation, and the augmented proliferative response to PDGF in PDZK1-/- VSM was abrogated by Bcr depletion. Furthermore, compared with wild-type Bcr overexpression, the introduction of a Bcr mutant incapable of PDZK1 binding into VSM cells yielded an exaggerated proliferative response to PDGF. Thus, PDZK1 has novel SR-BI-independent function in VSM that affords protection from neointima formation, and this involves PDZK1 suppression of VSM cell proliferation via an inhibitory interaction with Bcr.

  14. Cardiac troponin T and fast skeletal muscle denervation in ageing.

    Science.gov (United States)

    Xu, Zherong; Feng, Xin; Dong, Juan; Wang, Zhong-Min; Lee, Jingyun; Furdui, Cristina; Files, Daniel Clark; Beavers, Kristen M; Kritchevsky, Stephen; Milligan, Carolanne; Jin, Jian-Ping; Delbono, Osvaldo; Zhang, Tan

    2017-10-01

    Ageing skeletal muscle undergoes chronic denervation, and the neuromuscular junction (NMJ), the key structure that connects motor neuron nerves with muscle cells, shows increased defects with ageing. Previous studies in various species have shown that with ageing, type II fast-twitch skeletal muscle fibres show more atrophy and NMJ deterioration than type I slow-twitch fibres. However, how this process is regulated is largely unknown. A better understanding of the mechanisms regulating skeletal muscle fibre-type specific denervation at the NMJ could be critical to identifying novel treatments for sarcopenia. Cardiac troponin T (cTnT), the heart muscle-specific isoform of TnT, is a key component of the mechanisms of muscle contraction. It is expressed in skeletal muscle during early development, after acute sciatic nerve denervation, in various neuromuscular diseases and possibly in ageing muscle. Yet the subcellular localization and function of cTnT in skeletal muscle is largely unknown. Studies were carried out on isolated skeletal muscles from mice, vervet monkeys, and humans. Immunoblotting, immunoprecipitation, and mass spectrometry were used to analyse protein expression, real-time reverse transcription polymerase chain reaction was used to measure gene expression, immunofluorescence staining was performed for subcellular distribution assay of proteins, and electromyographic recording was used to analyse neurotransmission at the NMJ. Levels of cTnT expression in skeletal muscle increased with ageing in mice. In addition, cTnT was highly enriched at the NMJ region-but mainly in the fast-twitch, not the slow-twitch, muscle of old mice. We further found that the protein kinase A (PKA) RIα subunit was largely removed from, while PKA RIIα and RIIβ are enriched at, the NMJ-again, preferentially in fast-twitch but not slow-twitch muscle in old mice. Knocking down cTnT in fast skeletal muscle of old mice: (i) increased PKA RIα and reduced PKA RIIα at the NMJ; (ii

  15. Pelvic floor muscle training for secondary prevention of pelvic organ prolapse (PREVPROL): a multicentre randomised controlled trial.

    Science.gov (United States)

    Hagen, Suzanne; Glazener, Cathryn; McClurg, Doreen; Macarthur, Christine; Elders, Andrew; Herbison, Peter; Wilson, Don; Toozs-Hobson, Philip; Hemming, Christine; Hay-Smith, Jean; Collins, Marissa; Dickson, Sylvia; Logan, Janet

    2017-01-28

    Pelvic floor muscle training can reduce prolapse severity and symptoms in women seeking treatment. We aimed to assess whether this intervention could also be effective in secondary prevention of prolapse and the need for future treatment. We did this multicentre, parallel-group, randomised controlled trial at three centres in New Zealand and the UK. Women from a longitudinal study of pelvic floor function after childbirth were potentially eligible for inclusion. Women of any age who had stage 1-3 prolapse, but had not sought treatment, were randomly assigned (1:1), via remote computer allocation, to receive either one-to-one pelvic floor muscle training (five physiotherapy appointments over 16 weeks, and annual review) plus Pilates-based pelvic floor muscle training classes and a DVD for home use (intervention group), or a prolapse lifestyle advice leaflet (control group). Randomisation was minimised by centre, parity (three or less vs more than three deliveries), prolapse stage (above the hymen vs at or beyond the hymen), and delivery method (any vaginal vs all caesarean sections). Women and intervention physiotherapists could not be masked to group allocation, but allocation was masked from data entry researchers and from the trial statistician until after database lock. The primary outcome was self-reported prolapse symptoms (Pelvic Organ Prolapse Symptom Score [POP-SS]) at 2 years. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01171846. Between Dec 21, 2008, and Feb 24, 2010, in New Zealand, and Oct 27, 2010, and Sept 5, 2011, in the UK, we randomly assigned 414 women to the intervention group (n=207) or the control group (n=207). One participant in each group was excluded after randomisation, leaving 412 women for analysis. At baseline, 399 (97%) women had prolapse above or at the level of the hymen. The mean POP-SS score at 2 years was 3·2 (SD 3·4) in the intervention group versus 4·2 (SD 4·4) in the

  16. 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.

  17. 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

  18. Small molecules targeting LapB protein prevent Listeria attachment to catfish muscle.

    Directory of Open Access Journals (Sweden)

    Ali Akgul

    Full Text Available Listeria monocytogenes is a Gram-positive foodborne pathogen and the causative agent of listeriosis. L. monocytogenes lapB gene encodes a cell wall surface anchor protein, and mutation of this gene causes Listeria attenuation in mice. In this work, the potential role of Listeria LapB protein in catfish fillet attachment was investigated. To achieve this, boron-based small molecules designed to interfere with the active site of the L. monocytogenes LapB protein were developed, and their ability to prevent L. monocytogenes attachment to fish fillet was tested. Results indicated that seven out of nine different small molecules were effective in reducing the Listeria attachment to catfish fillets. Of these, three small molecules (SM3, SM5, and SM7 were highly effective in blocking Listeria attachment to catfish fillets. This study suggests an alternative strategy for reduction of L. monocytogenes contamination in fresh and frozen fish products.

  19. High-frequency, low-magnitude vibration does not prevent bone loss resulting from muscle disuse in mice following botulinum toxin injection.

    Science.gov (United States)

    Manske, Sarah L; Good, Craig A; Zernicke, Ronald F; Boyd, Steven K

    2012-01-01

    High-frequency, low-magnitude vibration enhances bone formation ostensibly by mimicking normal postural muscle activity. We tested this hypothesis by examining whether daily exposure to low-magnitude vibration (VIB) would maintain bone in a muscle disuse model with botulinum toxin type A (BTX). Female 16-18 wk old BALB/c mice (N = 36) were assigned to BTX-VIB, BTX-SHAM, VIB, or SHAM. BTX mice were injected with BTX (20 µL; 1 U/100 g body mass) into the left hindlimb posterior musculature. All mice were anaesthetized for 20 min/d, 5 d/wk, for 3 wk, and the left leg mounted to a holder. Through the holder, VIB mice received 45 Hz, ± 0.6 g sinusoidal acceleration without weight bearing. SHAM mice received no vibration. At baseline and 3 wk, muscle cross-sectional area (MCSA) and tibial bone properties (epiphysis, metaphysis and diaphysis) were assessed by in vivo micro-CT. Bone volume fraction in the metaphysis decreased 12 ± 9% and 7 ± 6% in BTX-VIB and BTX-SHAM, but increased in the VIB and SHAM. There were no differences in dynamic histomorphometry outcomes between BTX-VIB and BTX nor between VIB and SHAM. Thus, vibration did not prevent bone loss induced by a rapid decline in muscle activity nor produce an anabolic effect in normal mice. The daily loading duration was shorter than would be expected from postural muscle activity, and may have been insufficient to prevent bone loss. Based on the approach used in this study, vibration does not prevent bone loss in the absence of muscle activity induced by BTX.

  20. High-frequency, low-magnitude vibration does not prevent bone loss resulting from muscle disuse in mice following botulinum toxin injection.

    Directory of Open Access Journals (Sweden)

    Sarah L Manske

    Full Text Available High-frequency, low-magnitude vibration enhances bone formation ostensibly by mimicking normal postural muscle activity. We tested this hypothesis by examining whether daily exposure to low-magnitude vibration (VIB would maintain bone in a muscle disuse model with botulinum toxin type A (BTX. Female 16-18 wk old BALB/c mice (N = 36 were assigned to BTX-VIB, BTX-SHAM, VIB, or SHAM. BTX mice were injected with BTX (20 µL; 1 U/100 g body mass into the left hindlimb posterior musculature. All mice were anaesthetized for 20 min/d, 5 d/wk, for 3 wk, and the left leg mounted to a holder. Through the holder, VIB mice received 45 Hz, ± 0.6 g sinusoidal acceleration without weight bearing. SHAM mice received no vibration. At baseline and 3 wk, muscle cross-sectional area (MCSA and tibial bone properties (epiphysis, metaphysis and diaphysis were assessed by in vivo micro-CT. Bone volume fraction in the metaphysis decreased 12 ± 9% and 7 ± 6% in BTX-VIB and BTX-SHAM, but increased in the VIB and SHAM. There were no differences in dynamic histomorphometry outcomes between BTX-VIB and BTX nor between VIB and SHAM. Thus, vibration did not prevent bone loss induced by a rapid decline in muscle activity nor produce an anabolic effect in normal mice. The daily loading duration was shorter than would be expected from postural muscle activity, and may have been insufficient to prevent bone loss. Based on the approach used in this study, vibration does not prevent bone loss in the absence of muscle activity induced by BTX.

  1. Targeted inhibition of TGF-β results in an initial improvement but long-term deficit in force production after contraction-induced skeletal muscle injury.

    Science.gov (United States)

    Gumucio, Jonathan P; Flood, Michael D; Phan, Anthony C; Brooks, Susan V; Mendias, Christopher L

    2013-08-15

    Transforming growth factor-β (TGF-β) is a proinflammatory cytokine that regulates the response of many tissues following injury. Previous studies in our lab have shown that treating muscles with TGF-β results in a dramatic accumulation of type I collagen, substantial fiber atrophy, and a marked decrease in force production. Because TGF-β promotes atrophy and fibrosis, our objective was to investigate whether the inhibition of TGF-β after injury would enhance the recovery of muscle following injury. We hypothesized that inhibiting TGF-β after contraction-induced injury would improve the functional recovery of muscles by preventing muscle fiber atrophy and weakness, and by limiting the accumulation of fibrotic scar tissue. To test this hypothesis, we induced an injury using a series of in situ lengthening contractions to extensor digitorum longus muscles of mice treated with either a bioneutralizing antibody against TGF-β or a sham antibody. Compared with controls, muscles from mice receiving TGF-β inhibitor showed a greater recovery in force 3 days and 7 days after injury but had a decrease in force compared with controls at the 21-day time point. The early enhancement in force in the TGF-β inhibitor group was associated with an initial improvement in tissue morphology, but, at 21 days, while the control group was fully recovered, the TGF-β inhibitor group displayed an irregular extracellular matrix and an increase in atrogin-1 gene expression. These results indicate that the inhibition of TGF-β promotes the early recovery of muscle function but is detrimental overall to full muscle recovery following moderate to severe muscle 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. Live imaging of muscles in Drosophila metamorphosis: Towards high-throughput gene identification and function analysis.

    Science.gov (United States)

    Puah, Wee Choo; Wasser, Martin

    2016-03-01

    Time-lapse microscopy in developmental biology is an emerging tool for functional genomics. Phenotypic effects of gene perturbations can be studied non-invasively at multiple time points in chronological order. During metamorphosis of Drosophila melanogaster, time-lapse microscopy using fluorescent reporters allows visualization of alternative fates of larval muscles, which are a model for the study of genes related to muscle wasting. While doomed muscles enter hormone-induced programmed cell death, a smaller population of persistent muscles survives to adulthood and undergoes morphological remodeling that involves atrophy in early, and hypertrophy in late pupation. We developed a method that combines in vivo imaging, targeted gene perturbation and image analysis to identify and characterize genes involved in muscle development. Macrozoom microscopy helps to screen for interesting muscle phenotypes, while confocal microscopy in multiple locations over 4-5 days produces time-lapse images that are used to quantify changes in cell morphology. Performing a similar investigation using fixed pupal tissues would be too time-consuming and therefore impractical. We describe three applications of our pipeline. First, we show how quantitative microscopy can track and measure morphological changes of muscle throughout metamorphosis and analyze genes involved in atrophy. Second, our assay can help to identify genes that either promote or prevent histolysis of abdominal muscles. Third, we apply our approach to test new fluorescent proteins as live markers for muscle development. We describe mKO2 tagged Cysteine proteinase 1 (Cp1) and Troponin-I (TnI) as examples of proteins showing developmental changes in subcellular localization. Finally, we discuss strategies to improve throughput of our pipeline to permit genome-wide screens in the future. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Exercise quantity-dependent muscle hypertrophy in adult zebrafish (Danio rerio).

    Science.gov (United States)

    Hasumura, Takahiro; Meguro, Shinichi

    2016-07-01

    Exercise is very important for maintaining and increasing skeletal muscle mass, and is particularly important to prevent and care for sarcopenia and muscle disuse atrophy. However, the dose-response relationship between exercise quantity, duration/day, and overall duration and muscle mass is poorly understood. Therefore, we investigated the effect of exercise duration on skeletal muscle to reveal the relationship between exercise quantity and muscle hypertrophy in zebrafish forced to exercise. Adult male zebrafish were exercised 6 h/day for 4 weeks, 6 h/day for 2 weeks, or 3 h/day for 2 weeks. Flow velocity was adjusted to maximum velocity during continual swimming (initial 43 cm/s). High-speed consecutive photographs revealed that zebrafish mainly drove the caudal part. Additionally, X-ray micro computed tomography measurements indicated muscle hypertrophy of the mid-caudal half compared with the mid-cranial half part. The cross-sectional analysis of the mid-caudal half muscle revealed that skeletal muscle (red, white, or total) mass increased with increasing exercise quantity, whereas that of white muscle and total muscle increased only under the maximum exercise load condition of 6 h/day for 4 weeks. Additionally, the muscle fiver size distributions of exercised fish were larger than those from non-exercised fish. We revealed that exercise quantity, duration/day, and overall duration were correlated with skeletal muscle hypertrophy. The forced exercise model enabled us to investigate the relationship between exercise quantity and skeletal muscle mass. These results open up the possibility for further investigations on the effects of exercise on skeletal muscle in adult zebrafish.

  5. 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.

  6. 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.)

  7. Resveratrol prevents angiotensin II-induced hypertrophy of vascular smooth muscle cells through the transactivation of growth factor receptors.

    Science.gov (United States)

    Hossain, Ekhtear; Anand-Srivastava, Madhu B

    2017-08-01

    We previously showed that augmented levels of endogenous angiotensin II (AngII) contribute to vascular smooth muscle cell (VSMC) hypertrophy through the transactivation of growth factor receptors in spontaneously hypertensive rats. Resveratrol (RV), a polyphenolic component of red wine, has also been shown to attenuate AngII-evoked VSMC hypertrophy; however, the molecular mechanism mediating this response is obscure. The present study was therefore undertaken to examine whether RV could prevent AngII-induced VSMC hypertrophy through the transactivation of growth factor receptor and associated signaling pathways. AngII treatment of VSMC enhanced the protein synthesis that was attenuated towards control levels by RV pretreatment as well as by the inhibitors of NADPH oxidase, c-Src, and growth factor receptors. Furthermore, RV pretreatment also inhibited enhanced levels of superoxide anion, NADPH oxidase activity, increased expression of NADPH oxidase subunits, and phosphorylation of c-Src, EGF-R, PDGE-R, ERK1/2, and AKT1/2. In conclusion, these results indicate that RV attenuates AngII-induced VSMC hypertrophy through the inhibition of enhanced oxidative stress and activation of c-Src, growth factor receptors, and MAPK/AKT signaling. We suggest that RV could be used as a therapeutic agent in the treatment of vascular complications associated with hypertension and hypertrophy.

  8. Carbocalcitonin treatment in Sudeck's atrophy

    International Nuclear Information System (INIS)

    Nuti, R.; Vattimo, A.; Martini, G.; Turchetti, V.; Righi, G.A.

    1987-01-01

    The efficacy of new calcitonin, the amino analog of eel calcitonin (carboCT) on Sudeck's atrophy of the foot was investigated in 14 patients. CarboCT was administered at the dose of 40 Medical Research Council (MRC) units per day, and the duration of treatment was two to ten months. No adverse effects were noted. Bone pain and local edema decreased associated with improvement of motility. CarboCT induced a slight decrease in plasma calcium, plasma phosphate, and 24-hour urinary calcium excretion. An increase in cAMP/Cr ratio, an index of parathyroid function, was also observed (probably a manifestation of the hypocalcemic effect of calcitonin and secondary parathyroid stimulation). The whole body retention of 99mTc-MDP represents a valuable index of bone turnover, it decreased progressively and significantly on treatment. A dynamic study of local bone uptake of 99mTC-MDP was performed in eight patients. After carboCT therapy, statistically significant decreases in local blood flow, early uptake, and delayed uptake were appreciated in the involved foot. These findings lead to the conclusion that carboCT is effective in the treatment of Sudeck's atrophy

  9. Carbocalcitonin treatment in Sudeck's atrophy.

    Science.gov (United States)

    Nuti, R; Vattimo, A; Martini, G; Turchetti, V; Righi, G A

    1987-02-01

    The efficacy of new calcitonin, the amino analog of eel calcitonin (carboCT) on Sudeck's atrophy of the foot was investigated in 14 patients. CarboCT was administered at the dose of 40 Medical Research Council (MRC) units per day, and the duration of treatment was two to ten months. No adverse effects were noted. Bone pain and local edema decreased associated with improvement of motility. CarboCT induced a slight decrease in plasma calcium, plasma phosphate, and 24-hour urinary calcium excretion. An increase in cAMP/Cr ratio, an index of parathyroid function, was also observed (probably a manifestation of the hypocalcemic effect of calcitonin and secondary parathyroid stimulation). The whole body retention of 99mTc-MDP represents a valuable index of bone turnover, it decreased progressively and significantly on treatment. A dynamic study of local bone uptake of 99mTC-MDP was performed in eight patients. After carboCT therapy, statistically significant decreases in local blood flow, early uptake, and delayed uptake were appreciated in the involved foot. These findings lead to the conclusion that carboCT is effective in the treatment of Sudeck's atrophy.

  10. 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

  11. Regulation of Akt-mTOR, ubiquitin-proteasome and autophagy-lysosome pathways in locomotor and respiratory muscles during experimental sepsis in mice.

    Science.gov (United States)

    Morel, Jérome; Palao, Jean-Charles; Castells, Josiane; Desgeorges, Marine; Busso, Thierry; Molliex, Serge; Jahnke, Vanessa; Del Carmine, Peggy; Gondin, Julien; Arnould, David; Durieux, Anne Cécile; Freyssenet, Damien

    2017-09-07

    Sepsis induced loss of muscle mass and function contributes to promote physical inactivity and disability in patients. In this experimental study, mice were sacrificed 1, 4, or 7 days after cecal ligation and puncture (CLP) or sham surgery. When compared with diaphragm, locomotor muscles were more prone to sepsis-induced muscle mass loss. This could be attributed to a greater activation of ubiquitin-proteasome system and an increased myostatin expression. Thus, this study strongly suggests that the contractile activity pattern of diaphragm muscle confers resistance to atrophy compared to the locomotor gastrocnemius muscle. These data also suggest that a strategy aimed at preventing the activation of catabolic pathways and preserving spontaneous activity would be of interest for the treatment of patients with sepsis-induced neuromyopathy.

  12. 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

  13. 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.

  14. Intermittent whole-body vibration attenuates a reduction in the number of the capillaries in unloaded rat skeletal muscle.

    Science.gov (United States)

    Kaneguchi, Akinori; Ozawa, Junya; Kawamata, Seiichi; Kurose, Tomoyuki; Yamaoka, Kaoru

    2014-09-26

    Whole-body vibration has been suggested for the prevention of muscle mass loss and muscle wasting as an attractive measure for disuse atrophy. This study examined the effects of daily intermittent whole-body vibration and weight bearing during hindlimb suspension on capillary number and muscle atrophy in rat skeletal muscles. Sixty male Wistar rats were randomly divided into four groups: control (CONT), hindlimb suspension (HS), HS + weight bearing (WB), and HS + whole-body vibration (VIB) (n = 15 each). Hindlimb suspension was applied for 2 weeks in HS, HS + WB, and HS + VIB groups. During suspension, rats in HS + VIB group were placed daily on a vibrating whole-body vibration platform for 20 min. In HS + WB group, suspension was interrupted for 20 min/day, allowing weight bearing. Untreated rats were used as controls. Soleus muscle wet weights and muscle fiber cross-sectional areas (CSA) significantly decreased in HS, HS + WB, and HS + VIB groups compared with CONT group. Both muscle weights and CSA were significantly greater in HS + WB and HS + VIB groups compared with HS group. Capillary numbers (represented by capillary-to-muscle fiber ratio) were significantly smaller in all hindlimb suspension-treated groups compared with CONT group. However, a reduction in capillary number by unloading hindlimbs was partially prevented by whole-body vibration. These findings were supported by examining mRNA for angiogenic-related factors. Expression levels of a pro-angiogenic factor, vascular endothelial growth factor-A mRNA, were significantly lower in all hindlimb suspension-treated groups compared with CONT group. There were no differences among hindlimb suspension-treated groups. Expression levels of an anti-angiogenic factor, CD36 (receptor for thrombospondin-1) mRNA, were significantly higher in all hindlimb suspension-treated groups compared with CONT group. Among the hindlimb suspension-treated groups, expression of CD

  15. 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

  16. Seronegative Intestinal Villous Atrophy: A Diagnostic Challenge

    Directory of Open Access Journals (Sweden)

    Cláudio Martins

    2016-01-01

    Full Text Available Celiac disease is the most important cause of intestinal villous atrophy. Seronegative intestinal villous atrophy, including those that are nonresponsive to a gluten-free diet, is a diagnostic challenge. In these cases, before establishing the diagnosis of seronegative celiac disease, alternative etiologies of atrophic enteropathy should be considered. Recently, a new clinical entity responsible for seronegative villous atrophy was described—olmesartan-induced sprue-like enteropathy. Herein, we report two uncommon cases of atrophic enteropathy in patients with arterial hypertension under olmesartan, who presented with severe chronic diarrhea and significant involuntary weight loss. Further investigation revealed intestinal villous atrophy and intraepithelial lymphocytosis. Celiac disease and other causes of villous atrophy were ruled out. Drug-induced enteropathy was suspected and clinical improvement and histologic recovery were verified after olmesartan withdrawal. These cases highlight the importance for clinicians to maintain a high index of suspicion for olmesartan as a precipitant of sprue-like enteropathy.

  17. Myostatin Activates the Ubiquitin-Proteasome and Autophagy-Lysosome Systems Contributing to Muscle Wasting in Chronic Kidney Disease

    Science.gov (United States)

    Wang, Dong-Tao; Yang, Ya-Jun; Huang, Ren-Hua; Zhang, Zhi-Hua; Lin, Xin

    2015-01-01

    Our evidence demonstrated that CKD upregulated the expression of myostatin, TNF-α, and p-IkBa and downregulated the phosphorylation of PI3K, Akt, and FoxO3a, which were also associated with protein degradation and muscle atrophy. The autophagosome formation and protein expression of autophagy-related genes were increased in muscle of CKD rats. The mRNA level and protein expression of MAFbx and MuRF-1 were also upregulated in CKD rats, as well as proteasome activity of 26S. Moreover, activation of myostatin elicited by TNF-α induces C2C12 myotube atrophy via upregulating the expression of autophagy-related genes, including MAFbx and MuRF1 and proteasome subunits. Inactivation of FoxO3a triggered by PI3K inhibitor LY294002 prevented the myostatin-induced increase of expression of MuRF1, MAFbx, and LC3-II protein in C2C12 myotubes. The findings were further consolidated by using siRNA interference and overexpression of myostatin. Additionally, expression of myostatin was activated by TNF-α via a NF-κB dependent pathway in C2C12 myotubes, while inhibition of NF-κB activity suppressed myostatin and improved myotube atrophy. Collectively, myostatin mediated CKD-induced muscle catabolism via coordinate activation of the autophagy and the ubiquitin-proteasome systems. PMID:26448817

  18. Acoustic Correlates of Fatigue in Laryngeal Muscles: Findings for a Criterion-Based Prevention of Acquired Voice Pathologies

    Science.gov (United States)

    Boucher, Victor J.

    2008-01-01

    Purpose: The objective was to identify acoustic correlates of laryngeal muscle fatigue in conditions of vocal effort. Method: In a previous study, a technique of electromyography (EMG) served to define physiological signs of "voice fatigue" in laryngeal muscles involved in voicing. These signs correspond to spectral changes in contraction…

  19. 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

  20. 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)

  1. 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).

  2. Pelvic floor muscle training for prevention and treatment of urinary and faecal incontinence in antenatal and postnatal women.

    Science.gov (United States)

    Woodley, Stephanie J; Boyle, Rhianon; Cody, June D; Mørkved, Siv; Hay-Smith, E Jean C

    2017-12-22

    About one-third of women have urinary incontinence and up to one-tenth have faecal incontinence after childbirth. Pelvic floor muscle training (PFMT) is commonly recommended during pregnancy and after birth for both prevention and treatment of incontinence.This is an update of a review previously published in 2012. To determine the effectiveness of pelvic floor muscle training (PFMT) in the prevention or treatment of urinary and faecal incontinence in pregnant or postnatal women. We searched the Cochrane Incontinence Specialised Register (16 February 2017) and reference lists of retrieved studies. Randomised or quasi-randomised trials in pregnant or postnatal women. One arm of the trial included PFMT. Another arm was no PFMT, usual antenatal or postnatal care, another control condition, or an alternative PFMT intervention. Review authors independently assessed trials for inclusion and risk of bias. We extracted data and checked them for accuracy. Populations included: women who were continent (PFMT for prevention), women who were incontinent (PFMT for treatment) at randomisation and a mixed population of women who were one or the other (PFMT for prevention or treatment). We assessed quality of evidence using the GRADE approach. The review included 38 trials (17 of which were new for this update) involving 9892 women from 20 countries. Overall, trials were small to moderate sized, and the PFMT programmes and control conditions varied considerably and were often poorly described. Many trials were at moderate to high risk of bias. Other than two reports of pelvic floor pain, trials reported no harmful effects of PFMT.Prevention of urinary incontinence: compared with usual care, continent pregnant women performing antenatal PFMT may have had a lower risk of reporting urinary incontinence in late pregnancy (62% less; risk ratio (RR) for incontinence 0.38, 95% confidence interval (CI) 0.20 to 0.72; 6 trials, 624 women; low-quality evidence). Similarly, antenatal PFMT

  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. Stem cell-derived neurotrophic support for the neuromuscular junction in spinal muscular atrophy.

    Science.gov (United States)

    Wyatt, Tanya J; Keirstead, Hans S

    2010-11-01

    Spinal muscular atrophy (SMA) is a neurodegenerative disease characterized by specific degeneration of α-motor neurons in the spinal cord. The use of cell transplantation to restore lost function through cell replacement or prevent further degeneration of motor neurons and synapses through neurotrophic support heralds tremendous hope in the SMA field. Much research has been carried out in the last decade on the use of embryonic stem cells in cell replacement strategies for various neurodegenerative diseases. Cell replacement is contingent on the ability of transplanted cells to integrate and form new functional connections with host cells. In the case of SMA, cell replacement is a tall order in that axons of transplanted cells would be required to grow over long distances from the spinal cord through growth-averse terrain to synapse with muscles in the periphery. The efficacy of neurotrophic support is contingent on the ability of transplanted cells to secrete neurotrophins appropriate for degenerating motor neurons in the spinal cord or development/stability of the neuromuscular junction (NMJ) in the periphery. The reader will gain an understanding of the potential of neurotrophins to promote development of the NMJ in a diseased or injured environment. Neurotrophins play a major role in NMJ development and thus may be a key factor in the pathogenesis of NMJs in SMA. Further research into the signaling mechanisms involved in NMJ maturation may identify additional mechanisms by which transplanted cells may be of therapeutic benefit.

  5. Molecular Mechanisms of Obesity-Induced Osteoporosis and Muscle Atrophy

    OpenAIRE

    Roy, Bipradas; Curtis, Mary E.; Fears, Letimicia S.; Nahashon, Samuel N.; Fentress, Hugh M.

    2016-01-01

    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 ex...

  6. Periorbital muscle atrophy associated with topical bimatoprost therapy

    OpenAIRE

    Wang, Priscilla Xinhui; Koh, Victor Teck Chang; Cheng, Jin Fong

    2014-01-01

    Priscilla Xinhui Wang, Victor Teck Chang Koh, Jin Fong ChengDepartment of Ophthalmology, National University Health System, SingaporeAbstract: Topical Bimatoprost is a common and popular prostaglandin analog used as an ocular hypotensive agent in the treatment of glaucoma. Side effects include ocular hyperaemia, ocular pruritus, and periocular and iris pigmentary changes. Perioribital lipodystrophy is another well-documented outcome associated with chronic use of topical bimatoprost, which re...

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. Inducible satellite cell depletion attenuates skeletal muscle regrowth following a scald-burn injury.

    Science.gov (United States)

    Finnerty, Celeste C; McKenna, Colleen F; Cambias, Lauren A; Brightwell, Camille R; Prasai, Anesh; Wang, Ye; El Ayadi, Amina; Herndon, David N; Suman, Oscar E; Fry, Christopher S

    2017-11-01

    Severe burns result in significant skeletal muscle cachexia that impedes recovery. Activity of satellite cells, skeletal muscle stem cells, is altered following a burn injury and likely hinders regrowth of muscle. Severe burn injury induces satellite cell proliferation and fusion into myofibres with greater activity in muscles proximal to the injury site. Conditional depletion of satellite cells attenuates recovery of myofibre area and volume following a scald burn injury in mice. Skeletal muscle regrowth following a burn injury requires satellite cell activity, underscoring the therapeutic potential of satellite cells in the prevention of prolonged frailty in burn survivors. Severe burns result in profound skeletal muscle atrophy; persistent muscle atrophy and weakness are major complications that hamper recovery from burn injury. Many factors contribute to the erosion of muscle mass following burn trauma, and we have previously shown concurrent activation and apoptosis of muscle satellite cells following a burn injury in paediatric patients. To determine the necessity of satellite cells during muscle recovery following a burn injury, we utilized a genetically modified mouse model (Pax7 CreER -DTA) that allows for the conditional depletion of satellite cells in skeletal muscle. Additionally, mice were provided 5-ethynyl-2'-deoxyuridine to determine satellite cell proliferation, activation and fusion. Juvenile satellite cell-wild-type (SC-WT) and satellite cell-depleted (SC-Dep) mice (8 weeks of age) were randomized to sham or burn injury consisting of a dorsal scald burn injury covering 30% of total body surface area. Both hindlimb and dorsal muscles were studied at 7, 14 and 21 days post-burn. SC-Dep mice had >93% depletion of satellite cells compared to SC-WT (P satellite cell proliferation and fusion. Depletion of satellite cells impaired post-burn recovery of both muscle fibre cross-sectional area and volume (P satellite cells in the aetiology of lean

  13. A Possible Link between Gastric Mucosal Atrophy and Gastric Cancer after Helicobacter pylori Eradication.

    Directory of Open Access Journals (Sweden)

    Tomomitsu Tahara

    Full Text Available The effect of H. pylori eradication in gastric cancer prevention can be attributed to the improvement of atrophic gastritis, which is a known risk of gastric cancer. However, gastric cancer has also been diagnosed after long-term H. pylori eradication. This study aimed to clarify the association between gastric atrophy and gastric cancer after H. pylori eradication, including its clinicopathological features.A total of 55 consecutive patients with 64 early gastric cancers (EGCs diagnosed after H. pylori eradication were enrolled. The degree of endoscopic atrophy and the histological degrees of mononuclear cell infiltration, atrophy, and metaplasia in the corpus and adjacent mucosa of the EGCs were determined and scored.The majority of EGCs (63/64 were located within the endoscopically assessed atrophic mucosa or along the atrophic border. The adjacent mucosa of the EGCs presented significantly higher degrees of all histological parameters than in the corpus (mononuclear cell infiltration, 0.86+/-0.09 vs. 0.51+/-0.11, P = 0.016; atrophy, 1.77+/-0.13 vs. 0.65+/-0.14, P<0.0001; metaplasia, 1.68+/-0.13 vs. 0.48+/-0.1, P<0.0001. The degree of endoscopic atrophy improved in the patients with longer post-H. pylori eradication periods; however, this trend was not observed for the histological parameters, and high degrees of atrophy and metaplasia were observed in the adjacent mucosa of the EGCs compared with the corpus during all periods (all P<0.05. The histological degrees of atrophy and metaplasia in the adjacent mucosa were particularly higher in the patients who underwent eradication due to gastric ulcers.Severe gastric atrophy remained in the adjacent mucosa of the EGCs after H. pylori eradication, which may be linked to gastric carcinogenesis.

  14. Diagnosis of multiple system atrophy.

    Science.gov (United States)

    Palma, Jose-Alberto; Norcliffe-Kaufmann, Lucy; Kaufmann, Horacio

    2018-05-01

    Multiple system atrophy (MSA) may be difficult to distinguish clinically from other disorders, particularly in the early stages of the disease. An autonomic-only presentation can be indistinguishable from pure autonomic failure. Patients presenting with parkinsonism may be misdiagnosed as having Parkinson disease. Patients presenting with the cerebellar phenotype of MSA can mimic other adult-onset ataxias due to alcohol, chemotherapeutic agents, lead, lithium, and toluene, or vitamin E deficiency, as well as paraneoplastic, autoimmune, or genetic ataxias. A careful medical history and meticulous neurological examination remain the cornerstone for the accurate diagnosis of MSA. Ancillary investigations are helpful to support the diagnosis, rule out potential mimics, and define therapeutic strategies. This review summarizes diagnostic investigations useful in the differential diagnosis of patients with suspected MSA. Currently used techniques include structural and functional brain imaging, cardiac sympathetic imaging, cardiovascular autonomic testing, olfactory testing, sleep study, urological evaluation, and dysphagia and cognitive assessments. Despite advances in the diagnostic tools for MSA in recent years and the availability of consensus criteria for clinical diagnosis, the diagnostic accuracy of MSA remains sub-optimal. As other diagnostic tools emerge, including skin biopsy, retinal biomarkers, blood and cerebrospinal fluid biomarkers, and advanced genetic testing, a more accurate and earlier recognition of MSA should be possible, even in the prodromal stages. This has important implications as misdiagnosis can result in inappropriate treatment, patient and family distress, and erroneous eligibility for clinical trials of disease-modifying drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. 'Pharyngocise': Randomized Controlled Trial of Preventative Exercises to Maintain Muscle Structure and Swallowing Function During Head-and-Neck Chemoradiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Carnaby-Mann, Giselle, E-mail: gmann@phhp.ufl.edu [Department of Behavioral Science and Community Health, University of Florida, Gainesville, FL (United States); Crary, Michael A. [Department of Speech Language and Hearing Sciences, University of Florida, Gainesville, FL (United States); Schmalfuss, Ilona [Department of Radiology, North Florida/South Georgia Veterans Health System, Gainesville, FL (Georgia); Amdur, Robert [Department of Radiation Oncology, University of Florida, Gainesville, FL (United States)

    2012-05-01

    Purpose: Dysphagia after chemoradiotherapy is common. The present randomized clinical trial studied the effectiveness of preventative behavioral intervention for dysphagia compared with the 'usual care.' Methods and Materials: A total of 58 head-and-neck cancer patients treated with chemoradiotherapy were randomly assigned to usual care, sham swallowing intervention, or active swallowing exercises (pharyngocise). The intervention arms were treated daily during chemoradiotherapy. The primary outcome measure was muscle size and composition (determined by T{sub 2}-weighted magnetic resonance imaging). The secondary outcomes included functional swallowing ability, dietary intake, chemosensory function, salivation, nutritional status, and the occurrence of dysphagia-related complications. Results: The swallowing musculature (genioglossus, hyoglossuss, and mylohyoid) demonstrated less structural deterioration in the active treatment arm. The functional swallowing, mouth opening, chemosensory acuity, and salivation rate deteriorated less in the pharyngocise group. Conclusion: Patients completing a program of swallowing exercises during cancer treatment demonstrated superior muscle maintenance and functional swallowing ability.

  16. “Pharyngocise”: Randomized Controlled Trial of Preventative Exercises to Maintain Muscle Structure and Swallowing Function During Head-and-Neck Chemoradiotherapy

    International Nuclear Information System (INIS)

    Carnaby-Mann, Giselle; Crary, Michael A.; Schmalfuss, Ilona; Amdur, Robert

    2012-01-01

    Purpose: Dysphagia after chemoradiotherapy is common. The present randomized clinical trial studied the effectiveness of preventative behavioral intervention for dysphagia compared with the “usual care.” Methods and Materials: A total of 58 head-and-neck cancer patients treated with chemoradiotherapy were randomly assigned to usual care, sham swallowing intervention, or active swallowing exercises (pharyngocise). The intervention arms were treated daily during chemoradiotherapy. The primary outcome measure was muscle size and composition (determined by T 2 -weighted magnetic resonance imaging). The secondary outcomes included functional swallowing ability, dietary intake, chemosensory function, salivation, nutritional status, and the occurrence of dysphagia-related complications. Results: The swallowing musculature (genioglossus, hyoglossuss, and mylohyoid) demonstrated less structural deterioration in the active treatment arm. The functional swallowing, mouth opening, chemosensory acuity, and salivation rate deteriorated less in the pharyngocise group. Conclusion: Patients completing a program of swallowing exercises during cancer treatment demonstrated superior muscle maintenance and functional swallowing ability.

  17. 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)

  18. 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)

  19. Impaired physical function, loss of muscle mass and assessment of biomechanical properties in critical ill patients

    DEFF Research Database (Denmark)

    Poulsen, Jesper Brøndum

    2012-01-01

    Intensive care unit (ICU) admission is associated with muscle weakness and ICU survivors report sustained limitation of physical capacity for years after discharge. Limited information is available on the underlying biomechanical properties responsible for this muscle function impairment. A plaus......Intensive care unit (ICU) admission is associated with muscle weakness and ICU survivors report sustained limitation of physical capacity for years after discharge. Limited information is available on the underlying biomechanical properties responsible for this muscle function impairment....... A plausible contributor to the accentuated catabolic drive in ICU patients is a synergistic response to inflammation and inactivity leading to loss of muscle mass. As these entities are predominantly present in the early phase of ICU stay, interventions employed during this time frame may exhibit the greatest...... potential to counteract loss of muscle mass. Despite the obvious clinical significance of muscle atrophy for the functional impairment observed in ICU survivors, no preventive therapies have been identified as yet. The overall aim of the present dissertation is to characterize aspects of physical function...

  20. Chronic treatment with fluoxetine and sertraline prevents forced swimming test-induced hypercontractility of rat detrusor muscle.

    Science.gov (United States)

    Bilge, Sirri; Bozkurt, Ayhan; Bas, Duygu B; Aksoz, Elif; Savli, Evren; Ilkaya, Fatih; Kesim, Yuksel

    2008-01-01

    Serotonin (5-hydroxytryptamine, 5-HT) reuptake inhibitors represent important targets for the development of new treatments for detrusor overactivity and urinary incontinence. The present study was undertaken to investigate the effects of the forced swimming test (FST) on the contractile response of isolated rat detrusor muscle and to examine the effects of in vivo treatments of fluoxetine and sertraline on altered detrusor muscle contractility. Fluoxetine (20 mg/kg ip) and sertraline (10 mg/kg ip) were administered once a day for 14 days. Rats were exposed to the FST on the 15th day. After the test, detrusor muscles were removed and placed in organ baths, and the contraction responses induced by carbachol, potassium chloride (KCl) and electrical field stimulation (EFS) were recorded. The contractile responses of detrusor muscle strips to carbachol and electrical field stimulation were found to be increased at all carbachol doses and frequencies, respectively. FST also increased the contractile responses to KCl, which is used to test the differences in postreceptor-mediated contractions. The hypercontractile responses of detrusor strips to carbachol, EFS and KCl were abolished by treatment with both fluoxetine and sertraline. These treatments also decreased the immobility duration in the FST consistent with an antidepressant-like effect in this test. The results of this study provide the first evidence that FST increases contractility of the rat detrusor muscle, and this hypercontractility was abolished by chronic treatments of fluoxetine and sertraline at antidepressant doses by decreasing the postreceptor-mediated events.

  1. Imbalances in the Development of Muscle and Tendon as Risk Factor for Tendinopathies in Youth Athletes: A Review of Current Evidence and Concepts of Prevention

    Directory of Open Access Journals (Sweden)

    Falk Mersmann

    2017-12-01

    Full Text Available Tendons feature the crucial role to transmit the forces exerted by the muscles to the skeleton. Thus, an increase of the force generating capacity of a muscle needs to go in line with a corresponding modulation of the mechanical properties of the associated tendon to avoid potential harm to the integrity of the tendinous tissue. However, as summarized in the present narrative review, muscle and tendon differ with regard to both the time course of adaptation to mechanical loading as well as the responsiveness to certain types of mechanical stimulation. Plyometric loading, for example, seems to be a more potent stimulus for muscle compared to tendon adaptation. In growing athletes, the increased levels of circulating sex hormones might additionally augment an imbalanced development of muscle strength and tendon mechanical properties, which could potentially relate to the increasing incidence of tendon overload injuries that has been indicated for adolescence. In fact, increased tendon stress and strain due to a non-uniform musculotendinous development has been observed recently in adolescent volleyball athletes, a high-risk group for tendinopathy. These findings highlight the importance to deepen the current understanding of the interaction of loading and maturation and demonstrate the need for the development of preventive strategies. Therefore, this review concludes with an evidence-based concept for a specific loading program for increasing tendon stiffness, which could be implemented in the training regimen of young athletes at risk for tendinopathy. This program incorporates five sets of four contractions with an intensity of 85–90% of the isometric voluntary maximum and a movement/contraction duration that provides 3 s of high magnitude tendon strain.

  2. 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...

  3. 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.)

  4. 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.

  5. 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.

  6. 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

  7. 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

  8. 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

  9. Astaxanthin Supplementation Delays Physical Exhaustion and Prevents Redox Imbalances in Plasma and Soleus Muscles of Wistar Rats

    Directory of Open Access Journals (Sweden)

    Tatiana G. Polotow

    2014-12-01

    Full Text Available Astaxanthin (ASTA is a pinkish-orange carotenoid commonly found in marine organisms, especially salmon. ASTA is a powerful antioxidant and suggested to provide benefits for human health, including the inhibition of LDL oxidation, UV-photoprotection, and prophylaxis of bacterial stomach ulcers. Exercise is associated to overproduction of free radicals in muscles and plasma, with pivotal participation of iron ions and glutathione (GSH. Thus, ASTA was studied here as an auxiliary supplement to improve antioxidant defenses in soleus muscles and plasma against oxidative damage induced by exhaustive exercise. Long-term 1 mg ASTA/kg body weight (BW supplementation in Wistar rats (for 45 days significantly delayed time to exhaustion by 29% in a swimming test. ASTA supplementation increased scavenging/iron-chelating capacities (TEAC/FRAP and limited exercise-induced iron overload and its related pro-oxidant effects in plasma of exercising animals. On the other hand, ASTA induced significant mitochondrial Mn-dependent superoxide dismutase and cytosolic glutathione peroxidase antioxidant responses in soleus muscles that, in turn, increased GSH content during exercise, limited oxidative stress, and delayed exhaustion. We also provided significant discussion about a putative “mitochondrial-targeted” action of ASTA based on previous publications and on the positive results found in the highly mitochondrial populated (oxidative-type soleus muscles here.

  10. Lifelong physical activity prevents an age-related reduction in arterial and skeletal muscle nitric oxide bioavailability in humans

    DEFF Research Database (Denmark)

    Nyberg, Michael Permin; Blackwell, James R; Damsgaard, Ramsus

    2012-01-01

    studied the effect of ROS on systemic and skeletal muscle NO bioavailability and leg blood flow by infusion of the antioxidant N-acetylcysteine (NAC). Infusion of NAC increased the bioavailability of NO in OS, as evidenced by an increased concentration of stable metabolites of NO (NOx) in the arterial...

  11. Burn-induced increase in atrogin-1 and MuRF-1 in skeletal muscle is glucocorticoid independent but downregulated by IGF-I.

    Science.gov (United States)

    Lang, Charles H; Huber, Danuta; Frost, Robert A

    2007-01-01

    The present study determined whether thermal injury increases the expression of the ubiquitin (Ub) E3 ligases referred to as muscle ring finger (MuRF)-1 and muscle atrophy F-box (MAFbx; aka atrogin-1), which are muscle specific and responsible for the increased protein breakdown observed in other catabolic conditions. After 48 h of burn injury (40% total body surface area full-thickness scald burn) gastrocnemius weight was reduced, and this change was associated with an increased mRNA abundance for atrogin-1 and MuRF-1 (3.1- to 8-fold, respectively). Similarly, burn increased polyUb mRNA content in the gastrocnemius twofold. In contrast, there was no burn-induced atrophy of the soleus and no significant change in atrogin-1, MuRF-1, or polyUb mRNA. Burns also did not alter E3 ligase expression in heart. Four hours after administration of the anabolic agent insulin-like growth factor (IGF)-I to burned rats, the mRNA content of atrogin-1 and polyUb in gastrocnemius had returned to control values and the elevation in MuRF-1 was reduced 50%. In contrast, leucine did not alter E3 ligase expression. In a separate study, in vivo administration of the proteasome inhibitor Velcade prevented burn-induced loss of muscle mass determined at 48 h. Finally, administration of the glucocorticoid receptor antagonist RU-486 did not prevent burn-induced atrophy of the gastrocnemius or the associated elevation in atrogin-1, MuRF-1, or polyUb. In summary, the acute muscle wasting accompanying thermal injury is associated with a glucocorticoid-independent increase in the expression of several Ub E3 ligases that can be downregulated by IGF-I.

  12. Electrically Stimulated Antagonist Muscle Contraction Increased Muscle Mass and Bone Mineral Density of One Astronaut - Initial Verification on the International Space Station.

    Science.gov (United States)

    Shiba, Naoto; Matsuse, Hiroo; Takano, Yoshio; Yoshimitsu, Kazuhiro; Omoto, Masayuki; Hashida, Ryuki; Tagawa, Yoshihiko; Inada, Tomohisa; Yamada, Shin; Ohshima, Hiroshi

    2015-01-01

    Musculoskeletal atrophy is one of the major problems of extended periods of exposure to weightlessness such as on the International Space Station (ISS). We developed the Hybrid Training System (HTS) to maintain an astronaut's musculoskeletal system using an electrically stimulated antagonist to resist the volitional contraction of the agonist instead of gravity. The present study assessed the system's orbital operation capability and utility, as well as its preventative effect on an astronaut's musculoskeletal atrophy. HTS was attached to the non-dominant arm of an astronaut staying on the ISS, and his dominant arm without HTS was established as the control (CTR). 10 sets of 10 reciprocal elbow curls were one training session, and 12 total sessions of training (3 times per week for 4 weeks) were performed. Pre and post flight ground based evaluations were performed by Biodex (muscle performance), MRI (muscle volume), and DXA (BMD, lean [muscle] mass, fat mass). Pre and post training inflight evaluations were performed by a hand held dynamometer (muscle force) and a measuring tape (upper arm circumference). The experiment was completed on schedule, and HTS functioned well without problems. Isokinetic elbow extension torque (Nm) changed -19.4% in HTS, and -21.7% in CTR. Isokinetic elbow flexion torque changed -23.7% in HTS, and there was no change in CTR. Total Work (Joule) of elbow extension changed -8.3% in HTS, and +0.3% in CTR. For elbow flexion it changed -23.3% in HTS and -32.6% in CTR. Average Power (Watts) of elbow extension changed +22.1% in HTS and -8.0% in CTR. For elbow flexion it changed -6.5% in HTS and -4.8% in CTR. Triceps muscle volume according to MRI changed +11.7% and that of biceps was +2.1% using HTS, however -0.1% and -0.4% respectively for CTR. BMD changed +4.6% in the HTS arm and -1.2% for CTR. Lean (muscle) mass of the arm changed only +10.6% in HTS. Fat mass changed -12.6% in HTS and -6.4% in CTR. These results showed the orbital operation

  13. Electrically Stimulated Antagonist Muscle Contraction Increased Muscle Mass and Bone Mineral Density of One Astronaut - Initial Verification on the International Space Station.

    Directory of Open Access Journals (Sweden)

    Naoto Shiba

    Full Text Available Musculoskeletal atrophy is one of the major problems of extended periods of exposure to weightlessness such as on the International Space Station (ISS. We developed the Hybrid Training System (HTS to maintain an astronaut's musculoskeletal system using an electrically stimulated antagonist to resist the volitional contraction of the agonist instead of gravity. The present study assessed the system's orbital operation capability and utility, as well as its preventative effect on an astronaut's musculoskeletal atrophy.HTS was attached to the non-dominant arm of an astronaut staying on the ISS, and his dominant arm without HTS was established as the control (CTR. 10 sets of 10 reciprocal elbow curls were one training session, and 12 total sessions of training (3 times per week for 4 weeks were performed. Pre and post flight ground based evaluations were performed by Biodex (muscle performance, MRI (muscle volume, and DXA (BMD, lean [muscle] mass, fat mass. Pre and post training inflight evaluations were performed by a hand held dynamometer (muscle force and a measuring tape (upper arm circumference.The experiment was completed on schedule, and HTS functioned well without problems. Isokinetic elbow extension torque (Nm changed -19.4% in HTS, and -21.7% in CTR. Isokinetic elbow flexion torque changed -23.7% in HTS, and there was no change in CTR. Total Work (Joule of elbow extension changed -8.3% in HTS, and +0.3% in CTR. For elbow flexion it changed -23.3% in HTS and -32.6% in CTR. Average Power (Watts of elbow extension changed +22.1% in HTS and -8.0% in CTR. For elbow flexion it changed -6.5% in HTS and -4.8% in CTR. Triceps muscle volume according to MRI changed +11.7% and that of biceps was +2.1% using HTS, however -0.1% and -0.4% respectively for CTR. BMD changed +4.6% in the HTS arm and -1.2% for CTR. Lean (muscle mass of the arm changed only +10.6% in HTS. Fat mass changed -12.6% in HTS and -6.4% in CTR.These results showed the orbital

  14. Frontal parenchymal atrophy measures in multiple sclerosis.

    Science.gov (United States)

    Locatelli, Laura; Zivadinov, Robert; Grop, Attilio; Zorzon, Marino

    2004-10-01

    The aim of this study was to establish whether, in a cross-sectional study, the normalized measures of whole and regional brain atrophy correlate better with tests assessing the cognitive function than the absolute brain atrophy measures. The neuropsychological performances and disability have been assessed in 39 patients with relapsing-remitting multiple sclerosis (MS). T1- and T2-lesion load (LL) of total brain and frontal lobes (FLs) were measured using a reproducible semiautomated technique. The whole brain volume and the regional brain parenchymal volume (RBPV) of FLs were obtained using a computerized interactive program, which incorporates semiautomated and automated segmentation processes. Normalized measures of brain atrophy, i.e., brain parenchymal fraction (BPF) and regional brain parenchymal fraction (RBPF) of FLs, were calculated. The scan-rescan, inter- and intrarater coefficient of variation (COV) and intraclass correlation coefficient (ICC) have been estimated. The RBPF of FLs showed an acceptable level of reproducibility which ranged from 1.7% for intrarater variability to 3.2% for scan-rescan variability. The mean ICC was 0.88 (CI 0.82-0.93). The RBPF of FLs demonstrated stronger magnitudes of correlation with neuropsychological functioning, disability and quantitative MRI lesion measures than RBPV. These differences were statistically significant: PColor Word Interference test, Pcognitive functions, whereas BPAV did not. The correlation analysis results were supported by the results of multiple regression analysis which showed that only the normalized brain atrophy measures were associated with tests exploring the cognitive functions. These data suggest that RBPF is a reproducible and sensitive method for measuring frontal parenchymal atrophy. The normalized measures of whole and regional brain parenchymal atrophy should be preferred to absolute measures in future studies that correlate neuropsychological performances and brain atrophy measures

  15. Ingestion of glucose or sucrose prevents liver but not muscle glycogen depletion during prolonged endurance-type exercise in trained cyclists.

    Science.gov (United States)

    Gonzalez, Javier T; Fuchs, Cas J; Smith, Fiona E; Thelwall, Pete E; Taylor, Roy; Stevenson, Emma J; Trenell, Michael I; Cermak, Naomi M; van Loon, Luc J C

    2015-12-15

    The purpose of this study was to define the effect of glucose ingestion compared with sucrose ingestion on liver and muscle glycogen depletion during prolonged endurance-type exercise. Fourteen cyclists completed two 3-h bouts of cycling at 50% of peak power output while ingesting either glucose or sucrose at a rate of 1.7 g/min (102 g/h). Four cyclists performed an additional third test for reference in which only water was consumed. We employed (13)C magnetic resonance spectroscopy to determine liver and muscle glycogen concentrations before and after exercise. Expired breath was sampled during exercise to estimate whole body substrate use. After glucose and sucrose ingestion, liver glycogen levels did not show a significant decline after exercise (from 325 ± 168 to 345 ± 205 and 321 ± 177 to 348 ± 170 mmol/l, respectively; P > 0.05), with no differences between treatments. Muscle glycogen concentrations declined (from 101 ± 49 to 60 ± 34 and 114 ± 48 to 67 ± 34 mmol/l, respectively; P glycogen concentrations declined during exercise when only water was ingested. Both glucose and sucrose ingestion prevent liver glycogen depletion during prolonged endurance-type exercise. Sucrose ingestion does not preserve liver glycogen concentrations more than glucose ingestion. However, sucrose ingestion does increase whole body carbohydrate utilization compared with glucose ingestion. This trial was registered at https://www.clinicaltrials.gov as NCT02110836. Copyright © 2015 the American Physiological Society.

  16. Muscle Volume Increases Following 16 Weeks of Resistive Exercise Training with the Advanced Resistive Exercise Device (ARED) and Free Weights

    Science.gov (United States)

    Nash, R. E.; Loehr, J. A.; Lee, S. M. C.; English, K. L.; Evans, H.; Smith, S. A.; Hagan, R. D.

    2009-01-01

    Space flight-induced muscle atrophy, particularly in the postural and locomotorymuscles, may impair task performance during long-duration space missions and planetary exploration. High intensity free weight (FW) resistive exercise training has been shown to prevent atrophy during bed rest, a space flight analog. NASA developed the Advanced Resistive Exercise Device (ARED) to simulate the characteristics of FW exercise (i.e. constant mass, inertial force) and to be used as a countermeasure during International Space Station (ISS) missions. PURPOSE: To compare the efficacy of ARED and FW training to induce hypertrophy in specific muscle groups in ambulatory subjects prior to deploying ARED on the ISS. METHODS: Twenty untrained subjects were assigned to either the ARED (8 males, 3 females) or FW (6 males, 3 females) group and participated in a periodizedtraining protocol consisting of squat (SQ), heel raise (HR), and deadlift(DL) exercises 3 d wk-1 for 16 wks. SQ, HR, and DL muscle strength (1RM) was measured before, after 8 wks, and after 16 wks of training to prescribe exercise and measure strength changes. Muscle volume of the vastigroup (V), hamstring group (H), hip adductor group (ADD), medial gastrocnemius(MG), lateral gastrocnemius(LG), and deep posterior muscles including soleus(DP) was measured using MRI pre-and post-training. Consecutive cross-sectional images (8 mm slices with a 2 mm gap) were analyzed and summed. Anatomical references insured that the same muscle sections were analyzed pre-and post-training. Two-way repeated measures ANOVAs (ptraining devices. RESULTS: SQ, HR, and DL 1RM increased in both FW (SQ: 49+/-6%, HR: 12+/-2%, DL: 23+/-4%) and ARED (SQ: 31+/-4%, HR: 18+/-2%, DL: 23+/-3%) groups. Both groups increased muscle volume in the V (FW: 13+/-2%, ARED: 10+/-2%), H (FW: 3+/-1%, ARED: 3+/-1 %), ADD (FW: 15=/-2%, ARED: 10+/-1%), LG (FW: 7+/-2%, ARED: 4+/-1%), MG (FW: 7+/-2%, ARED: 5+/-2%), and DP (FW: 2+/-1%; ARED: 2+/-1%) after training. There

  17. D-TRP(8-γMSH Prevents the Effects of Endotoxin in Rat Skeletal Muscle Cells through TNFα/NF-KB Signalling Pathway.

    Directory of Open Access Journals (Sweden)

    Ana Belén Gómez-SanMiguel

    Full Text Available Sepsis induces anorexia and muscle wasting secondary to an increase in muscle proteolysis. Melanocyte stimulating hormones (MSH is a family of peptides that have potent anti-inflammatory effects. Melanocortin receptor-3 (MC3-R has been reported as the predominant anti-inflammatory receptor for melanocortins. The aim of this work was to analyse whether activation of MC3-R, by administration of its agonist D-Trp(8-γMSH, is able to modify the response of skeletal muscle to inflammation induced by lipopolysaccharide endotoxin (LPS or TNFα. Adult male rats were injected with 250 μg/kg LPS and/or 500 μg/kg D-Trp(8-γMSH 17:00 h and at 8:00 h the following day, and euthanized 4 hours afterwards. D-Trp(8-γMSH decreased LPS-induced anorexia and prevented the stimulatory effect of LPS on hypothalamic IL-1β, COX-2 and CRH as well as on serum ACTH and corticosterone. Serum IGF-I and its expression in liver and gastrocnemius were decreased in rats injected with LPS, but not in those that also received D-Trp(8-γMSH. However, D-Trp(8-γMSH was unable to modify the effect of LPS on IGFBP-3. In the gastrocnemius D-Trp(8-γMSH blocked LPS-induced decrease in pAkt, pmTOR, MHC I and MCH II, as well as the increase in pNF-κB(p65, FoxO1, FoxO3, LC3b, Bnip-3, Gabarap1, atrogin-1, MuRF1 and in LC3a/b lipidation. In L6 myotube cultures, D-Trp(8-γMSH was able to prevent TNFα-induced increase of NF-κB(p65 phosphorylation and decrease of Akt phosphorylation as well as of IGF-I and MHC I expression. These data suggest that MC3-R activation prevents the effect of endotoxin on skeletal wasting by modifying inflammation, corticosterone and IGF-I responses and also by directly acting on muscle cells through the TNFα/NF-κB(p65 pathway.

  18. 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.

  19. 99mTc-sestamibi muscle scintigraphy to assess the response to neuromuscular electrical stimulation of normal quadriceps femoris muscle

    International Nuclear Information System (INIS)

    Pekindil, Y.; Sarikaya, A.; Birtane, M.; Pekindil, G.; Salan, A.

    2001-01-01

    Neuromuscular electrical stimulation (NMES) is widely used for improving muscle strength by simultaneous contraction in the prevention of muscle atrophy. Although there exist many clinical methods for evaluating the therapeutic response of muscles, 99m Tc-sestamibi which is a skeletal muscle perfusion and metabolism agent has not previously been used for this purpose. The aim of our work was to ascertain whether 99m Tc-sestamibi muscle scintigraphy is useful in the monitoring of therapeutic response to NMES in healthy women. The study included 16 women aged between 21 and 45, with a mean age of 32.7±6.4. Both quadriceps femoris muscles (QFM) of each patient were studied. After randomization to remove the effect of the dominant side, one QFM of each patient was subjected to the NMES procedure for a period of 20 days. NMES was performed with an alternating biphasic rectangular current, from a computed electrical stimulator daily for 23 minutes. After measurement of skinfold thickness over the thigh, pre- and post-NMES girth measurements were assessed in centimeters. Sixty minutes after injections of 555 MBq 99m Tc-sestamibi, static images of the thigh were obtained for 5 minutes. The thigh-to-knee uptake ratio was calculated by semiquantitative analysis and normalized to body surface area (NUR=normalized uptake ratio). The difference between the pre and post NMES NUR values was significant (1.76±0.31 versus 2.25±0.38, p=0.0000). The percentage (%) increase in NUR values also well correlated with the % increase in thigh girth measurements (r=0.89, p=0.0000). These results indicated that 99m Tc-sestamibi muscle scintigraphy as a new tool may be useful in evaluating therapeutic response to NMES. (author)

  20. Tanning Shade Gradations of Models in Mainstream Fitness and Muscle Enthusiast Magazines: Implications for Skin Cancer Prevention in Men.

    Science.gov (United States)

    Basch, Corey H; Hillyer, Grace Clarke; Ethan, Danna; Berdnik, Alyssa; Basch, Charles E

    2015-07-01

    Tanned skin has been associated with perceptions of fitness and social desirability. Portrayal of models in magazines may reflect and perpetuate these perceptions. Limited research has investigated tanning shade gradations of models in men's versus women's fitness and muscle enthusiast magazines. Such findings are relevant in light of increased incidence and prevalence of melanoma in the United States. This study evaluated and compared tanning shade gradations of adult Caucasian male and female model images in mainstream fitness and muscle enthusiast magazines. Sixty-nine U.S. magazine issues (spring and summer, 2013) were utilized. Two independent reviewers rated tanning shade gradations of adult Caucasian male and female model images on magazines' covers, advertisements, and feature articles. Shade gradations were assessed using stock photographs of Caucasian models with varying levels of tanned skin on an 8-shade scale. A total of 4,683 images were evaluated. Darkest tanning shades were found among males in muscle enthusiast magazines and lightest among females in women's mainstream fitness magazines. By gender, male model images were 54% more likely to portray a darker tanning shade. In this study, images in men's (vs. women's) fitness and muscle enthusiast magazines portrayed Caucasian models with darker skin shades. Despite these magazines' fitness-related messages, pro-tanning images may promote attitudes and behaviors associated with higher skin cancer risk. To date, this is the first study to explore tanning shades in men's magazines of these genres. Further research is necessary to identify effects of exposure to these images among male readers. © The Author(s) 2014.

  1. Development of a Personalized Model for Pressure Ulcer Prevention Acutely Following Spinal Cord Injury: Biomarkers of Muscle Composition and Resilience

    Science.gov (United States)

    2016-10-01

    intramuscular fat (IMAT) compared to those with low IMAT. Specifically fatty acid binding protein 3 (FABP3 - expressed in muscle) and fatty acid binding...involved in fatty metabolism will be assessed at gene and protein levels using quantitative RT-PCR (qRT-PCR) and Western blotting respectively...Consistent data entry will be important so that all data can be analyzed directly from the electronic database. The basic structure of the model has

  2. 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

  3. Mathematical models of human paralyzed muscle after long-term training.

    Science.gov (United States)

    Law, L A Frey; 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 this study was to compare the accuracy of three muscle models, one linear and two nonlinear, for predicting paralyzed soleus muscle force after exposure to long-term FES training. Further, we contrasted the findings between the trained and untrained limbs. The three models' parameters were best fit to a single force train in the trained soleus muscle (N=4). Nine additional force trains (test trains) were predicted for each subject using the developed models. Model errors between predicted and experimental force trains were determined, including specific muscle force properties. The mean overall error was greatest for the linear model (15.8%) and least for the nonlinear Hill Huxley type model (7.8%). No significant error differences were observed between the trained versus untrained limbs, although model parameter values were significantly altered with training. This study confirmed that nonlinear models most accurately predict both trained and untrained paralyzed muscle force properties. Moreover, the optimized model parameter values were responsive to the relative physiological state of the paralyzed muscle (trained versus untrained). These findings are relevant for the design and control of neuro-prosthetic devices for those with SCI.

  4. 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.

  5. 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

  6. A case of hepatic atrophy by irradiation

    International Nuclear Information System (INIS)

    Fukumoto, Takumi; Ku, Yonson; Saitoh, Yoichi

    1994-01-01

    A 44-year-old woman was treated with 60 Co irradiation (total dose 6000 rads) focused on the right side porta hepatis under the diagnosis of cholangiocarcinoma in 1975. Seventeen years after the treatment, she was admitted to our institution because of dull pain at right hypochondriac region. Adominal CT demonstrated an extreme hepatic atrophy and tumor mass in the right lobe of the liver. In November, 1991 right trisegmentectomy was performed under the diagnosis of hepatocellular carcinoma. Laparotomy revealed the extreme atrophy of the right lobe and associated hypertrophy of the left lobe of the liver. In this case radiation hepatitis occurred after irradiation to the liver and it was followed by the extreme hepatic atrophy as a long term effect of high dose irradiation on the liver. (author)

  7. Development of a Personalized Model for Pressure Ulcer Prevention Acutely Following Spinal Cord Injury: Biomarkers of Muscle Composition and Resilience

    Science.gov (United States)

    2015-10-01

    15. SUBJECT TERMS Spinal cord injury, pressure ulcer prevention, biomarkers, personalized healthcare 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF...pressure ulcer prevention, biomarkers, personalized healthcare 3. Accomplishments Major Project Goals Task 1: Subject Recruitment and Data...months (Co-Investigator) Clinically translatable nanotechnology : hemostasis and neuroprotection New studies 09/30/14 -09/30/15 Started 01/01/15

  8. 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.

  9. 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

  10. Prevention

    DEFF Research Database (Denmark)

    Halken, S; Høst, A

    2001-01-01

    , breastfeeding should be encouraged for 4-6 months. In high-risk infants a documented extensively hydrolysed formula is recommended if exclusive breastfeeding is not possible for the first 4 months of life. There is no evidence for preventive dietary intervention neither during pregnancy nor lactation...... populations. These theories remain to be documented in proper, controlled and prospective studies. Breastfeeding and the late introduction of solid foods (>4 months) is associated with a reduced risk of food allergy, atopic dermatitis, and recurrent wheezing and asthma in early childhood. In all infants....... Preventive dietary restrictions after the age of 4-6 months are not scientifically documented....

  11. CT features of olivopontocerebellar atrophy in children

    International Nuclear Information System (INIS)

    Kumar, S.D.; Gururaj, A.K.; Jeans, W.D.

    1995-01-01

    Between 1990 and 1992, 14 children were seen in whom a clinical diagnosis of olivopontocerebellar atrophy (OPCA) had been made. The majority of patients presented with cerebellar ataxia and hypotonia. Five children had a family history of a similar illness in first-degree relatives. All cases had undergone clinical and neurologic examinations, routine laboratory tests and cranial CT. CT features were graded to quantitative the degree of atrophy in each cerebellar hemisphere, vermis and brain stem. All patients had varying degrees of atrophic changes of cerebellum, brain stem and cerebrum. These CT features appear to be distinctive enough to enable the diagnosis of OPCA to be made. (orig.)

  12. Progressive cerebral atrophy in neuromyelitis optica.

    Science.gov (United States)

    Warabi, Yoko; Takahashi, Toshiyuki; Isozaki, Eiji

    2015-12-01

    We report two cases of neuromyelitis optica patients with progressive cerebral atrophy. The patients exhibited characteristic clinical features, including elderly onset, secondary progressive tetraparesis and cognitive impairment, abnormally elevated CSF protein and myelin basic protein levels, and extremely highly elevated serum anti-AQP-4 antibody titer. Because neuromyelitis optica pathology cannot switch from an inflammatory phase to the degenerative phase until the terminal phase, neuromyelitis optica rarely appears as a secondary progressive clinical course caused by axonal degeneration. However, severe intrathecal inflammation and massive destruction of neuroglia could cause a secondary progressive clinical course associated with cerebral atrophy in neuromyelitis optica patients. © The Author(s), 2015.

  13. Effects of electrical stimulation and stretching on the adaptation of denervated skeletal muscle: implications for physical therapy Efeitos da eletroestimulação e do alongamento muscular sobre a adaptação do músculo desnervado: implicações para a fisioterapia

    Directory of Open Access Journals (Sweden)

    Tania F. Salvini

    2012-06-01

    Full Text Available BACKGROUND: This review will describe the main cellular mechanisms involved in the reduction and increase of myoproteins synthesis commonly associated with muscle atrophy and hypertrophy, respectively. OBJECTIVE: We analyzed the effects of electrical stimulation (ES and stretching exercise on the molecular pathways involved in muscle atrophy and hypertrophy. We also described the main effects and limits of these resources in the skeletal muscle, particularly on the denervated muscle. DISCUSSION: Recently, our studies showed that the ES applied in a similar manner as performed in clinical practice is able to attenuate the increase of genes expression involved in muscle atrophy. However, ES was not effective to prevent the loss of muscle mass caused by denervation. Regarding to stretching exercises, their mechanisms of action on the denervated muscle are not fully understood and studies on this area are scarce. Studies from our laboratory have found that stretching exercise increased the extracellular matrix remodeling and decreased genes expression related to atrophy in denervated muscle. Nevertheless, it was not enough to prevent muscle atrophy after denervation. CONCLUSIONS: In spite of the use of stretching exercise and ES in clinical practice in order to minimize the atrophy of denervated muscle, there is still lack of scientific evidence to justify the effectiveness of these resources to prevent muscle atrophy in denervated muscle.CONTEXTUALIZAÇÃO: Esta revisão abordará os principais mecanismos celulares envolvidos na redução e aumento da síntese de mioproteínas comumente associadas às situações de atrofia e hipertrofia muscular, respectivamente. OBJETIVO: Analisaremos os efeitos da estimulação elétrica (EE e do exercício de alongamento sobre as vias moleculares envolvidas na atrofia e hipertrofia muscular. Serão descritos os principais efeitos e os limites desses recursos no músculo esquelético, particularmente sobre o m

  14. 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...

  15. [Muscle and bone health as a risk factor of fall among the elderly. Kaigoyobou and prevention of falling].

    Science.gov (United States)

    Obuchi, Shuichi

    2008-06-01

    Kaigoyobou, prevention of long-term care use, is a comprehensive approach, including physical, nutritional, and social, to maintain independent living in the elderly. Prevention of falling is one useful method of Kaigoyobou. From literature review, post-fall syndrome should be primarily eliminated in the elderly since falling rate of the elderly with the falling history reported significantly greater falling rate than the other community dwelling elderly. The ability to avoid falling when they trip or slip during walking may be the most important physical function needed to be intervened. In order to train elderly person successfully, nutritional intervention need to be considered into fall prevention program.

  16. Effects of Preventative Ankle Taping on Planned Change-of-Direction and Reactive Agility Performance and Ankle Muscle Activity in Basketballers

    Directory of Open Access Journals (Sweden)

    Matthew D. Jeffriess, Adrian B. Schultz, Tye S. McGann, Sa