Persistent muscle fiber regeneration in long term denervation. Past, present, future

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Ugo Carraro

2015-03-01

Full Text Available Despite the ravages of long term denervation there is structural and ultrastructural evidence for survival of muscle fibers in mammals, with some fibers surviving at least ten months in rodents and 3-6 years in humans. Further, in rodents there is evidence that muscle fibers may regenerate even after repeated damage in the absence of the nerve, and that this potential is maintained for several months after denervation. While in animal models permanently denervated muscle sooner or later loses the ability to contract, the muscles may maintain their size and ability to function if electrically stimulated soon after denervation. Whether in mammals, humans included, this is a result of persistent de novo formation of muscle fibers is an open issue we would like to explore in this review. During the past decade, we have studied muscle biopsies from the quadriceps muscle of Spinal Cord Injury (SCI patients suffering with Conus and Cauda Equina syndrome, a condition that fully and irreversibly disconnects skeletal muscle fibers from their damaged innervating motor neurons. We have demonstrated that human denervated muscle fibers survive years of denervation and can be rescued from severe atrophy by home-based Functional Electrical Stimulation (h-bFES. Using immunohistochemistry with both non-stimulated and the h-bFES stimulated human muscle biopsies, we have observed the persistent presence of muscle fibers which are positive to labeling by an antibody which specifically recognizes the embryonic myosin heavy chain (MHCemb. Relative to the total number of fibers present, only a small percentage of these MHCemb positive fibers are detected, suggesting that they are regenerating muscle fibers and not pre-existing myofibers re-expressing embryonic isoforms. Although embryonic isoforms of acetylcholine receptors are known to be re-expressed and to spread from the end-plate to the sarcolemma of muscle fibers in early phases of muscle denervation, we suggest

Diffusion-weighted MRI of denervated muscle: a clinical and experimental study

International Nuclear Information System (INIS)

Holl, Nathalie; Bierry, Guillaume; Moser, Thomas; Dietemann, Jean-Louis; Kremer, Stephane; Echaniz-Laguna, Andoni; Mohr, Michel; Loeffler, Jean-Philippe

2008-01-01

The aim of this study was to investigate skeletal muscle denervation using diffusion-weighted magnetic resonance imaging (DWMRI). Sciatic nerve axotomy was performed in a group of nine New Zealand White rabbits, and electromyographic (EMG), pathological, and DWMRI studies were conducted on ipsilateral hamstring muscles 1 and 8 days after axotomy. In addition, DWMRI studies were carried out on leg muscles of ten patients with acute and subacute lumbosacral radiculopathy. High intensity signals on short tau inversion recovery (STIR) magnetic resonance imaging and an increased apparent diffusion coefficient (ADC) were observed in denervated muscles of the animals 1 and 8 days after axotomy as well as in denervated muscles of the patients with radiculopathy. In the clinical study, ADC was 1.26±0.18 x 10 -9 m 2 /s in normal muscle and increased to 1.56±0.23 x 10 -9 m 2 /s in denervated muscles (p =0.0016). In animals, EMG and muscle pathological studies were normal 1 day after axotomy, and the muscles demonstrated spontaneous activity on EMG and neurogenic atrophy on histological studies 7 days later. This DWMRI study demonstrates that enlargement of extracellular fluid space in muscle denervation is an early phenomenon occurring several days before the appearance of EMG and histological abnormalities. (orig.)

Three-dimensional architecture of the whole human soleus muscle in vivo

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Finni, Taija; D’Souza, Arkiev; Eguchi, Junya; Clarke, Elizabeth C.; Herbert, Robert D.

2018-01-01

Background Most data on the architecture of the human soleus muscle have been obtained from cadaveric dissection or two-dimensional ultrasound imaging. We present the first comprehensive, quantitative study on the three-dimensional anatomy of the human soleus muscle in vivo using diffusion tensor imaging (DTI) techniques. Methods We report three-dimensional fascicle lengths, pennation angles, fascicle curvatures, physiological cross-sectional areas and volumes in four compartments of the soleus at ankle joint angles of 69 ± 12° (plantarflexion, short muscle length; average ± SD across subjects) and 108 ± 7° (dorsiflexion, long muscle length) of six healthy young adults. Microdissection and three-dimensional digitisation on two cadaveric muscles corroborated the compartmentalised structure of the soleus, and confirmed the validity of DTI-based muscle fascicle reconstructions. Results The posterior compartments of the soleus comprised 80 ± 5% of the total muscle volume (356 ± 58 cm3). At the short muscle length, the average fascicle length, pennation angle and curvature was 37 ± 8 mm, 31 ± 3° and 17 ± 4 /m, respectively. We did not find differences in fascicle lengths between compartments. However, pennation angles were on average 12° larger (p < 0.01) in the posterior compartments than in the anterior compartments. For every centimetre that the muscle-tendon unit lengthened, fascicle lengths increased by 3.7 ± 0.8 mm, pennation angles decreased by −3.2 ± 0.9° and curvatures decreased by −2.7 ± 0.8 /m. Fascicles in the posterior compartments rotated almost twice as much as in the anterior compartments during passive lengthening. Discussion The homogeneity in fascicle lengths and inhomogeneity in pennation angles of the soleus may indicate a functionally different role for the anterior and posterior compartments. The data and techniques presented here demonstrate how DTI can be used to obtain detailed, quantitative measurements of the

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.

Usefulness of muscle denervation as an MRI sign of peripheral nerve pathology

International Nuclear Information System (INIS)

Lisle, D. A.; Johnstone, S. A.

2007-01-01

Full text: Peripheral nerve disorders may be classified into compressive or entrapment neuropathies and non-compressive neuropathies. Muscle denervation recognized on MRI may be a useful sign in the diagnosis of peripheral nerve disorders. Acute or subacute denervation results in prolonged T 2 relaxation time, producing increased signal in skeletal muscle on short tau inversion-recovery and fat-suppressed T 2 -weighted images. Chronic denervation produces fatty atrophy of skeletal muscles, resulting in increased muscle signal on T 1 -weighted images. This review will outline and illustrate the various ways that muscle denervation as seen on MRI may assist in the diagnosis and localization of peripheral nerve disorders

Soleus muscle H-reflex monitoring in endoscopic surgery under general anesthesia percutaneous interlaminar approach.

Science.gov (United States)

Wang, Huixue; Gao, Yingji; Ji, Lixin; Bai, Wanshan

2018-05-01

The clinical value of soleus muscle H-reflex monitoring in general anesthesia percutaneous interlaminar approach was investigated. A total of 80 cases with unilateral L5-S1 disc herniation between January 2015 and October 2016 were randomly divided into control group (without soleus muscle H-reflex monitoring, n=40) and observation group (with soleus muscle H-reflex monitoring, n=40). Results showed that the operation time of the observation group was shorter than that of the control group (Ph after operation, the amplitude of H-reflex in diseased side soleus muscle was significantly lower than that in healthy side (Ph postoperatively, the latency of H-reflex in diseased side soleus muscle was shorter than that of healthy side (PH-reflex latency in soleus muscle were significantly lower (PH-reflex monitoring can effectively reduce the damage to the nerve roots under percutaneous endoscopic intervertebral endoscopic surgery under general anesthesia, improve the accuracy of surgery, reduce the complications, shorten the operation time and reduce the surgical bleeding, which is more beneficial to patients smooth recovery.

Soleus muscle injury: sensitivity of ultrasound patterns

Energy Technology Data Exchange (ETDEWEB)

Balius, Ramon [Sport Catalan Council, Generalitat de Catalunya, Barcelona (Spain); Clinica CMI Diagonal, Barcelona (Spain); Rodas, Gil [F.C. Barcelona Medical Services, Barcelona (Spain); Pedret, Carles [Clinica CMI Diagonal, Barcelona (Spain); Clinica Mapfre de Medicina del Tenis, Sports Medicine and Imaging Department, Barcelona (Spain); Centre de Diagnostic per Imatge de Tarragona, Tarragona (Spain); Capdevila, Lluis [Universitat Autonoma de Barcelona, Laboratory of Sport Psychology, Barcelona (Spain); Alomar, Xavier [Clinica Creu Blanca, Barcelona (Spain); Bong, David A. [Instituto Poal de Reumatologia, Barcelona (Spain)

2014-06-15

To assess the sensitivity of ultrasound in detecting soleus muscle lesions diagnosed on magnetic resonance imaging (MRI) and to characterize their location, ultrasound pattern, and evolution. Ultrasound and MRI studies were performed between May 2009 and February 2013 on all patients who presented to the Medical Services Clinic of the Catalan Sport Council with the initial onset of sharp pain in the calf compatible with injury of the soleus muscle. An inter-observer ultrasound reliability study was also performed. A total of 55 cases of soleus injury were studied prospectively (22 with right leg involvement, 33 left) by ultrasound and MRI, which was utilized as the ''gold standard.'' In MRI studies, 24 cases (43.7 %) had myofascial injuries that were localized in the posterior aponeurosis (PMF) in 15 cases (27.3 %) and in the anterior aponeurosis (AMF) in 9 (16.4 %). Thirty-one cases (56.3 %) were musculotendinous injuries, with 9 cases (16.4 %) in the medial aponeurosis (MMT), 11 cases (20 %) in the lateral aponeurosis (LMT), and 11 cases (20 %) in the central tendon (CMT). In comparison to MRI, ultrasound was able to detect injury to the soleus in 27.2 % of cases. No injuries were detected by ultrasound alone. Posterior myofascial injuries were more likely to be detected by ultrasound than anterior myofascial injuries or all types of musculotendinous injuries. Ultrasound patterns for each type of injury were described. Ultrasound is not a sensitive technique for detecting and assessing soleus traumatic tears compared with MRI, although the sensitivity is enhanced by a thorough anatomically based ultrasound examination. Timing of the ultrasound examination may be of importance. Each type of soleus injury appears to have a characteristic ultrasound pattern based on a defect of connective expansions, the existence of small myofascial filiform collections, and the rarefaction of the fibrillar area. (orig.)

Soleus muscle injury: sensitivity of ultrasound patterns.

Science.gov (United States)

Balius, Ramon; Rodas, Gil; Pedret, Carles; Capdevila, Lluís; Alomar, Xavier; Bong, David A

2014-06-01

To assess the sensitivity of ultrasound in detecting soleus muscle lesions diagnosed on magnetic resonance imaging (MRI) and to characterize their location, ultrasound pattern, and evolution. Ultrasound and MRI studies were performed between May 2009 and February 2013 on all patients who presented to the Medical Services Clinic of the Catalan Sport Council with the initial onset of sharp pain in the calf compatible with injury of the soleus muscle. An inter-observer ultrasound reliability study was also performed. A total of 55 cases of soleus injury were studied prospectively (22 with right leg involvement, 33 left) by ultrasound and MRI, which was utilized as the "gold standard." In MRI studies, 24 cases (43.7%) had myofascial injuries that were localized in the posterior aponeurosis (PMF) in 15 cases (27.3%) and in the anterior aponeurosis (AMF) in 9 (16.4%). Thirty-one cases (56.3%) were musculotendinous injuries, with 9 cases (16.4%) in the medial aponeurosis (MMT), 11 cases (20%) in the lateral aponeurosis (LMT), and 11 cases (20%) in the central tendon (CMT). In comparison to MRI, ultrasound was able to detect injury to the soleus in 27.2% of cases. No injuries were detected by ultrasound alone. Posterior myofascial injuries were more likely to be detected by ultrasound than anterior myofascial injuries or all types of musculotendinous injuries. Ultrasound patterns for each type of injury were described. Ultrasound is not a sensitive technique for detecting and assessing soleus traumatic tears compared with MRI, although the sensitivity is enhanced by a thorough anatomically based ultrasound examination. Timing of the ultrasound examination may be of importance. Each type of soleus injury appears to have a characteristic ultrasound pattern based on a defect of connective expansions, the existence of small myofascial filiform collections, and the rarefaction of the fibrillar area.

Soleus muscle injury: sensitivity of ultrasound patterns

International Nuclear Information System (INIS)

Balius, Ramon; Rodas, Gil; Pedret, Carles; Capdevila, Lluis; Alomar, Xavier; Bong, David A.

2014-01-01

To assess the sensitivity of ultrasound in detecting soleus muscle lesions diagnosed on magnetic resonance imaging (MRI) and to characterize their location, ultrasound pattern, and evolution. Ultrasound and MRI studies were performed between May 2009 and February 2013 on all patients who presented to the Medical Services Clinic of the Catalan Sport Council with the initial onset of sharp pain in the calf compatible with injury of the soleus muscle. An inter-observer ultrasound reliability study was also performed. A total of 55 cases of soleus injury were studied prospectively (22 with right leg involvement, 33 left) by ultrasound and MRI, which was utilized as the ''gold standard.'' In MRI studies, 24 cases (43.7 %) had myofascial injuries that were localized in the posterior aponeurosis (PMF) in 15 cases (27.3 %) and in the anterior aponeurosis (AMF) in 9 (16.4 %). Thirty-one cases (56.3 %) were musculotendinous injuries, with 9 cases (16.4 %) in the medial aponeurosis (MMT), 11 cases (20 %) in the lateral aponeurosis (LMT), and 11 cases (20 %) in the central tendon (CMT). In comparison to MRI, ultrasound was able to detect injury to the soleus in 27.2 % of cases. No injuries were detected by ultrasound alone. Posterior myofascial injuries were more likely to be detected by ultrasound than anterior myofascial injuries or all types of musculotendinous injuries. Ultrasound patterns for each type of injury were described. Ultrasound is not a sensitive technique for detecting and assessing soleus traumatic tears compared with MRI, although the sensitivity is enhanced by a thorough anatomically based ultrasound examination. Timing of the ultrasound examination may be of importance. Each type of soleus injury appears to have a characteristic ultrasound pattern based on a defect of connective expansions, the existence of small myofascial filiform collections, and the rarefaction of the fibrillar area. (orig.)

Elevated interstitial fluid volume in rat soleus muscles by hindlimb unweighting

DEFF Research Database (Denmark)

Kandarian, S C; Boushel, Robert Christopher; Schulte, Lars

1991-01-01

) by tail suspension. Soleus muscles were studied after 28 days and compared with those from five age-matched control (C) rats. Interstitial fluid volume ([3H]inulin space) and maximum tetanic tension (Po) were measured in vitro at 25 degrees C. Soleus muscles atrophied 58% because of unweighting (C = 147...

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.

beta-adrenergic effects on carbohydrate metabolism in the unweighted rat soleus muscle

Science.gov (United States)

Kirby, Christopher R.; Tischler, Marc E.

1990-01-01

The effect of unweighting on the response of the soleus-muscle carbohydrate metabolism to a beta-adrenergic agonist (isoproterenol) was investigated in rats that were subjected to three days of tail-cast suspension. It was found that isoproterenol promoted glycogen degradation in soleus from suspended rats to a higher degree than in weighted soleus from control rats, and had no effect in unweighted digitorum longus. However, isoproterenol did not have a greater inhibitory effect on the net uptake of tritium-labeled 2-deoxy-glucose by the unweighted soleus and that isoproterenol inhibited hexose phosphorylation less in the unweighted than in the control muscle.

Diagnostic signs of motor neuropathy in MR neurography: Nerve lesions and muscle denervation

International Nuclear Information System (INIS)

Schwarz, Daniel; Pham, Mirko; Bendszus, Martin; Baeumer, Philipp; Weiler, Markus; Heiland, Sabine

2015-01-01

To investigate the diagnostic contribution of T2-w nerve lesions and of muscle denervation in peripheral motor neuropathies by magnetic resonance neurography (MRN). Fifty-one patients with peripheral motor neuropathies underwent high-resolution MRN by large coverage axial T2-w sequences of the upper arm, elbow, and forearm. Images were evaluated by two blinded readers for T2-w signal alterations of median, ulnar, and radial nerves, and for denervation in respective target muscle groups. All 51 patients displayed nerve lesions in at least one of three nerves, and 43 out of 51 patients showed denervation in at least one target muscle group of these nerves. In 21 out of 51 patients, the number of affected nerves matched the number of affected target muscle groups. In the remaining 30 patients, T2-w lesions were encountered more frequently than target muscle group denervation. In 153 nerve-muscle pairs, 72 showed denervation, but only one had increased muscle signal without a lesion in the corresponding nerve. MRN-based diagnosis of peripheral motor neuropathies is more likely by visualization of peripheral nerve lesions than by denervation in corresponding target muscles. Increased muscular T2-w signal without concomitant nerve lesions should raise suspicion of an etiology other than peripheral neuropathy. (orig.)

Diagnostic signs of motor neuropathy in MR neurography: Nerve lesions and muscle denervation

Energy Technology Data Exchange (ETDEWEB)

Schwarz, Daniel; Pham, Mirko; Bendszus, Martin; Baeumer, Philipp [Heidelberg University Hospital, Department of Neuroradiology, Heidelberg (Germany); Weiler, Markus [Heidelberg University Hospital, Department of Neurology, Heidelberg (Germany); German Cancer Research Center (DKFZ), Clinical Cooperation Unit Neurooncology, Heidelberg (Germany); Heiland, Sabine [Heidelberg University Hospital, Section of Experimental Radiology, Department of Neuroradiology, Heidelberg (Germany)

2015-05-01

To investigate the diagnostic contribution of T2-w nerve lesions and of muscle denervation in peripheral motor neuropathies by magnetic resonance neurography (MRN). Fifty-one patients with peripheral motor neuropathies underwent high-resolution MRN by large coverage axial T2-w sequences of the upper arm, elbow, and forearm. Images were evaluated by two blinded readers for T2-w signal alterations of median, ulnar, and radial nerves, and for denervation in respective target muscle groups. All 51 patients displayed nerve lesions in at least one of three nerves, and 43 out of 51 patients showed denervation in at least one target muscle group of these nerves. In 21 out of 51 patients, the number of affected nerves matched the number of affected target muscle groups. In the remaining 30 patients, T2-w lesions were encountered more frequently than target muscle group denervation. In 153 nerve-muscle pairs, 72 showed denervation, but only one had increased muscle signal without a lesion in the corresponding nerve. MRN-based diagnosis of peripheral motor neuropathies is more likely by visualization of peripheral nerve lesions than by denervation in corresponding target muscles. Increased muscular T2-w signal without concomitant nerve lesions should raise suspicion of an etiology other than peripheral neuropathy. (orig.)

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.

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.

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

Directory of Open Access Journals (Sweden)

Franziska Lang

2017-07-01

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

Comparative decline of the protein profiles of nebulin in response to denervation in skeletal muscle

Energy Technology Data Exchange (ETDEWEB)

Wei, Jih-Hua [Department of Internal Medicine, Min-Sheng General Hospital, Taoyuan, Taiwan (China); Chang, Nen-Chung [Division of Cardiology, Department of Internal Medicine, College of Medicine, Taipei Medical University Hospital, Taipei, Taiwan (China); Chen, Sy-Ping [Department of Nursing, Chang Gung University of Science and Technology, Taoyuan, Taiwan (China); Geraldine, Pitchairaj [Department of Animal Science, School of Life Sciences, Bharathidasan University, Tiruchirappalli, Tamil Nadu (India); Jayakumar, Thanasekaran, E-mail: tjaya_2002@yahoo.co.in [Department of Pharmacology and Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); Fong, Tsorng-Harn, E-mail: thfong@tmu.edu.tw [Department of Anatomy and Cell Biology, College of Medicine, Taipei Medical University, Taipei, Taiwan (China)

2015-10-09

The sliding filament model of the sarcomere was developed more than half a century ago. This model, consisting only of thin and thick filaments, has been efficacious in elucidating many, but not all, features of skeletal muscle. Work during the 1980s revealed the existence of two additional filaments: the giant filamentous proteins titin and nebulin. Nebulin, a giant myofibrillar protein, acts as a protein ruler to maintain the lattice arrays of thin filaments and plays a role in signal transduction and contractile regulation. However, the change of nebulin and its effect on thin filaments in denervation-induced atrophic muscle remains unclear. The purpose of this study is to examine the content and pattern of nebulin, myosin heavy chain (MHC), actin, and titin in innervated and denervated tibialis anterior (TA) muscles of rats using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), densitometry and electron microscopic (EM) analyses. The results revealed that denervation induced muscle atrophy is accompanied by decreased nebulin content in a time-dependent manner. For instant, the levels of nebulin in denervated muscles were markedly (P < 0.05) decreased, about 24.6% and 40.2% in comparison with innervated muscle after denervation of 28 and 56 days, respectively. The nebulin/MHC, nebulin/actin, and nebulin/titin ratios were decreased, suggesting a concomitant reduction of nebulin in denervated muscle. Moreover, a western blotting assay proved that nebulin declined faster than titin on 28 and 56 days of denervated muscle. In addition, EM study revealed that the disturbed arrangements of myofilaments and a disorganized contractile apparatus were also observed in denervated muscle. Overall, the present study provides evidence that nebulin is more sensitive to the effect of denervation than MHC, actin, and titin. Nebulin decline indeed resulted in disintegrate of thin filaments and shortening of sarcomeres. - Highlights: • We successfully

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

Directory of Open Access Journals (Sweden)

Fabio Francini

2010-09-01

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

Denervation in murine fast-twitch muscle: short-term physiological changes and temporal expression profiling.

Science.gov (United States)

Raffaello, Anna; Laveder, Paolo; Romualdi, Chiara; Bean, Camilla; Toniolo, Luana; Germinario, Elena; Megighian, Aram; Danieli-Betto, Daniela; Reggiani, Carlo; Lanfranchi, Gerolamo

2006-03-13

Denervation deeply affects muscle structure and function, the alterations being different in slow and fast muscles. Because the effects of denervation on fast muscles are still controversial, and high-throughput studies on gene expression in denervated muscles are lacking, we studied gene expression during atrophy progression following denervation in mouse tibialis anterior (TA). The sciatic nerve was cut close to trochanter in adult CD1 mice. One, three, seven, and fourteen days after denervation, animals were killed and TA muscles were dissected out and utilized for physiological experiments and gene expression studies. Target cDNAs from TA muscles were hybridized on a dedicated cDNA microarray of muscle genes. Seventy-one genes were found differentially expressed. Microarray results were validated, and the expression of relevant genes not probed on our array was monitored by real-time quantitative PCR (RQ-PCR). Nuclear- and mitochondrial-encoded genes implicated in energy metabolism were consistently downregulated. Among genes implicated in muscle contraction (myofibrillar and sarcoplasmic reticulum), genes typical of fast fibers were downregulated, whereas those typical of slow fibers were upregulated. Electrophoresis and Western blot showed less pronounced changes in myofibrillar protein expression, partially confirming changes in gene expression. Isometric tension of skinned fibers was little affected by denervation, whereas calcium sensitivity decreased. Functional studies in mouse extensor digitorum longus muscle showed prolongation in twitch time parameters and shift to the left in force-frequency curves after denervation. We conclude that, if studied at the mRNA level, fast muscles appear not less responsive than slow muscles to the interruption of neural stimulation.

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

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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.

Magnetic resonance imaging patterns of mononeuropathic denervation in muscles with dual innervation

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Sneag, Darryl B.; Lee, Susan C.; Melisaratus, Darius P. [Hospital for Special Surgery, Department of Radiology and Imaging, New York, NY (United States); Feinberg, Joseph H. [Physical Medicine and Rehabilitation, Hospital for Special Surgery, New York, NY (United States); Amber, Ian [MedStar Georgetown University Hospital, Department of Radiology, DC, Washington (United States)

2017-12-15

Magnetic resonance imaging (MRI) of mononeuropathy in muscles with dual innervation depicts geographic denervation corresponding to the affected nerve. Knowledge of the normal distribution of a muscle's neural supply is clinically relevant as partial muscle denervation represents a potential imaging pitfall that can be confused with other pathology, such as muscle strain. This article reviews the normal innervation pattern of extremity muscles with dual supply, providing illustrative examples of mononeuropathy affecting such muscles. (orig.)

Magnetic resonance imaging patterns of mononeuropathic denervation in muscles with dual innervation

International Nuclear Information System (INIS)

Sneag, Darryl B.; Lee, Susan C.; Melisaratus, Darius P.; Feinberg, Joseph H.; Amber, Ian

2017-01-01

Magnetic resonance imaging (MRI) of mononeuropathy in muscles with dual innervation depicts geographic denervation corresponding to the affected nerve. Knowledge of the normal distribution of a muscle's neural supply is clinically relevant as partial muscle denervation represents a potential imaging pitfall that can be confused with other pathology, such as muscle strain. This article reviews the normal innervation pattern of extremity muscles with dual supply, providing illustrative examples of mononeuropathy affecting such muscles. (orig.)

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

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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.

Are skeletal muscles independent actuators? Force transmission from soleus muscle in the cat

NARCIS (Netherlands)

Maas, H.; Sandercock, T.G.

2008-01-01

It is unclear if skeletal muscles act mechanically as independent actuators. The purpose of the present study was to investigate force transmission from soleus (SO) muscle for physiological lengths as well as relative positions in the intact cat hindlimb. We hypothesized that force transmission from

Heat shock transcription factor 1-deficiency attenuates overloading-associated hypertrophy of mouse soleus muscle.

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Koya, Tomoyuki; Nishizawa, Sono; Ohno, Yoshitaka; Goto, Ayumi; Ikuta, Akihiro; Suzuki, Miho; Ohira, Tomotaka; Egawa, Tatsuro; Nakai, Akira; Sugiura, Takao; Ohira, Yoshinobu; Yoshioka, Toshitada; Beppu, Moroe; Goto, Katsumasa

2013-01-01

Hypertrophic stimuli, such as mechanical stress and overloading, induce stress response, which is mediated by heat shock transcription factor 1 (HSF1), and up-regulate heat shock proteins (HSPs) in mammalian skeletal muscles. Therefore, HSF1-associated stress response may play a key role in loading-associated skeletal muscle hypertrophy. The purpose of this study was to investigate the effects of HSF1-deficiency on skeletal muscle hypertrophy caused by overloading. Functional overloading on the left soleus was performed by cutting the distal tendons of gastrocnemius and plantaris muscles for 4 weeks. The right muscle served as the control. Soleus muscles from both hindlimbs were dissected 2 and 4 weeks after the operation. Hypertrophy of soleus muscle in HSF1-null mice was partially inhibited, compared with that in wild-type (C57BL/6J) mice. Absence of HSF1 partially attenuated the increase of muscle wet weight and fiber cross-sectional area of overloaded soleus muscle. Population of Pax7-positive muscle satellite cells in HSF1-null mice was significantly less than that in wild-type mice following 2 weeks of overloading (pmuscle hypertrophy might be attributed to the greater and prolonged enhancement of IL-6 expression. HSF1 and/or HSF1-mediated stress response may, in part, play a key role in loading-induced skeletal muscle hypertrophy.

Three-O-methylglucose transport in soleus muscle of bacteremic rats

International Nuclear Information System (INIS)

Westfall, M.V.; Sayeed, M.M.

1987-01-01

Basal and insulin-stimulated soleus muscle 3-O-[ 14 C]merhylglucose ([ 14 C]-3-O-MG) transport was studied in vitro and in vivo during bacteremia in rats. Fasted rats were injected with Escherichia coli to produce bacteremia (B), and controls (C) received saline. In vitro studies using soleus muscles were carried out 8 of 12 hr after bacterial injection, and transport was measured using the rate coefficient (λ = min/sup /minus/1/). Although insulin-stimulated [ 14 C]-3-O-MG transport was decreased in 12-h bacteremic rat muscles the basal [ 14 C]-3-O-MG transport was rate coefficient was elevated. For in vivo studies, [ 14 C]-3-O-MG with or without insulin was injected into rats 10-40 min prior to removing soleus muscles at 12 h postbacterial or postsaline injection. Transport was measured as the ratio of [ 14 C]-3-O-MG/sub intracell//[ 14 C]-3-O-MG/sub extracell/. Basal ratios were not different and muscles from both control and bacteremic rats responded comparably to insulin with increased [ 14 C]-3-O-MG transport during the initial 30 min. At 35-40 min postinsulin injection there was a further stimulation of [ 14 C]-3-O-MG transport in control but not in 12-h bacteremic rat muscles. The changes in [ 14 C]-3-O-MG transport observed in vitro and in vivo after 12 h of bacteremia may be due to circulating mediators and/or changes in membrane function

Catalase-positive microperoxisomes in rat soleus and extensor digitorum longus muscle fiber types

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Riley, Danny A.; Bain, James L. W.; Ellis, Stanley

1988-01-01

The size, distribution, and content of catalase-reactive microperoxisomes were investigated cytochemically in three types of muscle fibers from the soleus and the extensor digitorum longus (EDL) of male rats. Muscle fibers were classified on the basis of the mitochondrial content and distribution, the Z-band widths, and the size and shape of myofibrils as the slow-twitch oxidative (SO), the fast-twitch oxidative glycolytic (FOG), and the fast-twitch glycolytic (FG) fibers. It was found that both the EDL and soleus SO fibers possessed the largest microperoxisomes. A comparison of microperoxisome number per muscle fiber area or the microperoxisome area per fiber area revealed following ranking, starting from the largest number and the area-ratio values: soleus SO, EDL SO, EDL FOG, and EDL FG.

Expression of TGF-β1 and CTGF Is Associated with Fibrosis of Denervated Sternocleidomastoid Muscles in Mice.

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Liu, Fei; Tang, Weifang; Chen, Donghui; Li, Meng; Gao, Yinna; Zheng, Hongliang; Chen, Shicai

2016-01-01

Injury to the recurrent laryngeal nerve often leads to permanent vocal cord paralysis, which has a significant negative impact on the quality of life. Long-term denervation can induce laryngeal muscle fibrosis, which obstructs the muscle recovery after laryngeal reinnervation. However, the mechanisms of fibrosis remain unclear. In this study, we aimed to analyze the changes in the expression of fibrosis-related factors, including transforming growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF), and α-smooth muscle actin (α-SMA) in denervated skeletal muscles using a mouse model of accessory nerve transection. Because of the small size, we used sternocleidomastoid muscles instead of laryngeal muscles for denervation experiments. Masson's trichrome staining showed that the grade of atrophy and fibrosis of muscles became more severe with time, but showed a plateau at 4 weeks after denervation, followed by a slow decrease. Quantitative assessment and immunohistochemistry showed that TGF-β1 expression peaked at 1 week after denervation (p muscle cells were detected at 1 week after denervation, peaked at 2 weeks (p muscle fibrosis. They may induce the differentiation of myoblasts into myofibroblasts, as characterized by the activation of α-SMA. These findings may provide insights on key pathological processes in denervated skeletal muscle fibrosis and develop novel therapeutic strategies.

Cardiac troponin T and fast skeletal muscle denervation in ageing.

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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

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.

Case report 376: Accessory (anomalous) soleus muscle

International Nuclear Information System (INIS)

Apple, J.S.; Khoury, M.B.; Martinez, S.; Nunley, J.A.

1986-01-01

In summary, a case has been presented of a 24-year-old woman who developed pain in the left lower extremity while jogging. Physical examination showed a soft, palpable mass medial and anterior to the Achilles tendon in the left lower extremity. Although a lipoma was suspected, plain films and CT studies indicated clearly that the mass was not of fatty density. In fact, the density of the mass was equivalent to adjacent muscles. The mass itself was lying in the soft tissues of the left ankle tissue. An open biopsy showed a normal muscle which represented an accessory soleus muscle - a muscle known to be anomalous on accoasion and reported as being symptomatic or asymptomatic in different individuals. (orig./SHA)

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

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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.

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

Increased response to insulin of glucose metabolism in the 6-day unloaded rat soleus muscle

Science.gov (United States)

Henriksen, Erik J.; Tischler, Marc E.; Johnson, David G.

1986-01-01

Hind leg muscles of female rats were unloaded by tail cast suspension for 6 days. In the fresh-frozen unloaded soleus, the significantly greater concentration of glycogen correlated with a lower activity ratio of glycogen phosphorylase (p less than 0.02). The activity ratio of glycogen synthase also was lower (p less than 0.001), possibly due to the higher concentration of glycogen. In isolated unloaded soleus, insulin (0.1 milliunit/ml) increased the oxidation of D(U-C-14) glucose, release of lactate and pyruvate, incorporation of D-(U-C-14) glucose into glycogen, and the concentration of glucose 6-phosphate more (p less than 0.05) than in the weight-bearing soleus. At physiological doses of insulin, the percent of maximal uptake of 2-deoxy-D-(1,2-H-3) glucose/muscle also was greater in the unloaded soleus. Unloading of the soleus increased, by 50 percent the concentration of insuling receptors, due to no decrease in total receptor number during muscle atrophy. This increase may account for the greater response of glucose metabolism to insulin in this muscle. The extensor digitorum longus, which generally shows little response to unloading, displayed no differential response of glucose metabolism to insulin.

Functional Echomyography: thickness, ecogenicity, contraction and perfusion of the LMN denervated human muscle before and during h-bFES

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Riccardo Zanato

2010-03-01

Full Text Available Permanent denervated muscles were evaluated by ultrasound to monitor changes in morphology, thickness, contraction-relaxation kinetics and perfusion due to the electrical stimulation program of the Rise2-Italy project. In a case of monolateral lesion, morphology and ultrasonographic structure of the denervated muscles changed during the period of stimulation from a pattern typical of complete denervation-induced muscle atrophy to a pattern which might be considered “normal” when detected in an old patient. Thickness improved significantly more in the middle third of the denervated muscle, reaching the same value as the contralateral innervated muscle. Contraction-relaxation kinetics, measured by recording the muscle movements during electrical stimulation, showed an abnormal behavior of the chronically denervated muscle during the relaxation phase, which resulted to be significantly longer than in normal muscle. The long-term denervated muscles analyzed with Echo Doppler showed at rest a low resistance arterial flow that became pulsed during and after electrical stimulation. As expected, the ultra sound measured electrical stimulation-induced hyperemia lasted longer than the stimulation period. The higher than normal energy of the delivered electrical stimuli of the Vienna home-based Functional Electrical Stimulation strategy (h-b FES demonstrate that the explored muscles were still almost completely denervated during the one-year of training. In conclusion, this pilot study confirms the usefulness of Functional Echomyography in the follow-up and the positive effects of h-b FES of denervated muscles.

Improved sphincter contractility after allogenic muscle-derived progenitor cell injection into the denervated rat urethra.

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Cannon, Tracy W; Lee, Ji Youl; Somogyi, George; Pruchnic, Ryan; Smith, Christopher P; Huard, Johnny; Chancellor, Michael B

2003-11-01

To study the physiologic outcome of allogenic transplant of muscle-derived progenitor cells (MDPCs) in the denervated female rat urethra. MDPCs were isolated from muscle biopsies of normal 6-week-old Sprague-Dawley rats and purified using the preplate technique. Sciatic nerve-transected rats were used as a model of stress urinary incontinence. The experimental group was divided into three subgroups: control, denervated plus 20 microL saline injection, and denervated plus allogenic MDPCs (1 to 1.5 x 10(6) cells) injection. Two weeks after injection, urethral muscle strips were prepared and underwent electrical field stimulation. The pharmacologic effects of d-tubocurare, phentolamine, and tetrodotoxin on the urethral strips were assessed by contractions induced by electrical field stimulation. The urethral tissues also underwent immunohistochemical staining for fast myosin heavy chain and CD4-activated lymphocytes. Urethral denervation resulted in a significant decrease of the maximal fast-twitch muscle contraction amplitude to only 8.77% of the normal urethra and partial impairment of smooth muscle contractility. Injection of MDPCs into the denervated sphincter significantly improved the fast-twitch muscle contraction amplitude to 87.02% of normal animals. Immunohistochemistry revealed a large amount of new skeletal muscle fiber formation at the injection site of the urethra with minimal inflammation. CD4 staining showed minimal lymphocyte infiltration around the MDPC injection sites. Urethral denervation resulted in near-total abolishment of the skeletal muscle and partial impairment of smooth muscle contractility. Allogenic MDPCs survived 2 weeks in sciatic nerve-transected urethra with minimal inflammation. This is the first report of the restoration of deficient urethral sphincter function through muscle-derived progenitor cell tissue engineering. MDPC-mediated cellular urethral myoplasty warrants additional investigation as a new method to treat stress urinary

Advanced age-related denervation and fiber-type grouping in skeletal muscle of SOD1 knockout mice.

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Kostrominova, Tatiana Y

2010-11-30

In this study skeletal muscles from 1.5- and 10-month-old Cu/Zn superoxide dismutase (SOD1) homozygous knockout (JLSod1(-/-)) mice obtained from The Jackson Laboratory (C57Bl6/129SvEv background) were compared with muscles from age- and sex-matched heterozygous (JLSod1(+/-)) littermates. The results of this study were compared with previously published data on two different strains of Sod1(-/-) mice: one from Dr. Epstein's laboratory (ELSod1(-/-); C57Bl6 background) and the other from Cephalon, Inc. (CSod1(-/-); 129/CD-1 background). Grouping of succinate dehydrogenase-positive fibers characterized muscles of Sod1(-/-) mice from all three strains. The 10-month-old Sod1(-/-)C and JL mice displayed pronounced denervation of the gastrocnemius muscle, whereas the ELSod1(-/-) mice displayed a small degree of denervation at this age, but developed accelerated age-related denervation later on. Denervation markers were up-regulated in skeletal muscle of 10-month-old JLSod1(-/-) mice. This study is the first to show that metallothionein mRNA and protein expression was up-regulated in the skeletal muscle of 10-month-old JLSod1(-/-) mice and was mostly localized to the small atrophic muscle fibers. In conclusion, all three strains of Sod1(-/-) mice develop accelerated age-related muscle denervation, but the genetic background has significant influence on the progress of denervation. Copyright © 2010 Elsevier Inc. All rights reserved.

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

Science.gov (United States)

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

2014-11-01

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

Ultra structure of the denervated vocal muscle mechanically in hogs (sus scrofa domestica

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Leão, Henrique Zaquia

2010-03-01

Full Text Available Introduction: The literature is not clear in the ultra-structural manifestations of the vocal wrinkles after neural wound. Objective: To verify the alterations that occur in a vocal fold mechanically denervated. Method: In this prospective study, it were utilized 15 hogs of commercial race (Sus scrofa domesticates, with age of 4 to 12 weeks. The animals were distributed in three groups, chosen at random. Everybody was submitted to the denervation of the right vocal fold, with surgical removal of a segment with three centimeters of the recurring right laryngeal nerve. After 45, 90 and 180 days of the operations, it was proceeded the biopsy of the vocal muscles, it was prosecuted the samples for transmission electron microscopy and, for the ultra-structural study, utilized the transmission electron microscopy Philips, model EM208S. Results: The biopsied groups with 45 and 90 days after operation of mechanical denervation, presented disorganization miofibrilar, only vestigial lines Z in many samples, as well like altered mithochondrions presenting limited sizes, and matrix mithocondrial rarefied with rare mithocondrial cristae present. The biopsied group with 180 days after operation of denervation, presented regular sarcomeres, mithocondrions with sizes and regular number with correct positioning between the sarcomerical units. Conclusion: The finds in the ultra-structure of the vocal muscles suggest to re enervation of the muscle being that the muscular mithochondrions were the most sensible structures to the denervated condition, successions by the cytoarchiteture of the miofibrilas; the finds in the ultra-structure of the vocal muscles suggests to reinervation of the muscle in the period of approximately six months.

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.

Acute rhabdomyolysis of the soleus muscle induced by a lightning strike: magnetic resonance and scintigraphic findings

Energy Technology Data Exchange (ETDEWEB)

Watanabe, Naofumi; Inaoka, Tsutomu; Shuke, Noriyuki; Takahashi, Koji; Aburano, Tamio [Asahikawa Medical College, Department of Radiology, Asahikawa (Japan); Chisato, Naoyuki; Go, Kazutomo [Asahikawa Medical College, Department of Emergency Medicine, Asahikawa (Japan); Nochi, Hitoshi [Asahikawa Medical College, Department of Orthopaedic Surgery, Asahikawa (Japan)

2007-07-15

Among natural disasters, a lightning strike is a rare but potentially life-threatening phenomenon. If victims survive a cardiac arrest due to instantaneous passage of an exceptionally high voltage electric charge through the whole body, they may be afflicted with various complications such as muscle necrosis resulting in acute renal failure. In this article, we report a case of a 54-year-old man with acute rhabdomyolysis of the left soleus muscle associated with a lightning strike. T2-weighted and short-tau inversion recovery MR images showed a high signal intensity in the left soleus muscle. A whole-body bone scintigram showed abnormal uptakes in the left soleus muscle and the dorsal aspect of the left foot. MR and scintigraphic evaluations were very useful in depicting the site and extent of muscle damage. Since the patient showed a surprisingly high level of serum creatine kinase, the added information was very valuable for determining the patient's management. (orig.)

Acute rhabdomyolysis of the soleus muscle induced by a lightning strike: magnetic resonance and scintigraphic findings

International Nuclear Information System (INIS)

Watanabe, Naofumi; Inaoka, Tsutomu; Shuke, Noriyuki; Takahashi, Koji; Aburano, Tamio; Chisato, Naoyuki; Go, Kazutomo; Nochi, Hitoshi

2007-01-01

Among natural disasters, a lightning strike is a rare but potentially life-threatening phenomenon. If victims survive a cardiac arrest due to instantaneous passage of an exceptionally high voltage electric charge through the whole body, they may be afflicted with various complications such as muscle necrosis resulting in acute renal failure. In this article, we report a case of a 54-year-old man with acute rhabdomyolysis of the left soleus muscle associated with a lightning strike. T2-weighted and short-tau inversion recovery MR images showed a high signal intensity in the left soleus muscle. A whole-body bone scintigram showed abnormal uptakes in the left soleus muscle and the dorsal aspect of the left foot. MR and scintigraphic evaluations were very useful in depicting the site and extent of muscle damage. Since the patient showed a surprisingly high level of serum creatine kinase, the added information was very valuable for determining the patient's management. (orig.)

The effects of denervation, reinnervation, and muscle imbalance on functional muscle length and elbow flexion contracture following neonatal brachial plexus injury.

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Weekley, Holly; Nikolaou, Sia; Hu, Liangjun; Eismann, Emily; Wylie, Christopher; Cornwall, Roger

2012-08-01

The pathophysiology of paradoxical elbow flexion contractures following neonatal brachial plexus injury (NBPI) is incompletely understood. The current study tests the hypothesis that this contracture occurs by denervation-induced impairment of elbow flexor muscle growth. Unilateral forelimb paralysis was created in mice in four neonatal (5-day-old) BPI groups (C5-6 excision, C5-6 neurotomy, C5-6 neurotomy/repair, and C5-T1 global excision), one non-neonatal BPI group (28-day-old C5-6 excision), and two neonatal muscle imbalance groups (triceps tenotomy ± C5-6 excision). Four weeks post-operatively, motor function, elbow range of motion, and biceps/brachialis functional lengths were assessed. Musculocutaneous nerve (MCN) denervation and reinnervation were assessed immunohistochemically. Elbow flexion motor recovery and elbow flexion contractures varied inversely among the neonatal BPI groups. Contracture severity correlated with biceps/brachialis shortening and MCN denervation (relative axon loss), with no contractures occurring in mice with MCN reinnervation (presence of growth cones). No contractures or biceps/brachialis shortening occurred following non-neonatal BPI, regardless of denervation or reinnervation. Neonatal triceps tenotomy did not cause contractures or biceps/brachialis shortening, nor did it worsen those following neonatal C5-6 excision. Denervation-induced functional shortening of elbow flexor muscles leads to variable elbow flexion contractures depending on the degree, permanence, and timing of denervation, independent of muscle imbalance. Copyright © 2012 Orthopaedic Research Society.

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

Permanent LMN denervation of human skeletal muscle and recovery by h-b FES: management and monitoring

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Helmut Kern

2010-09-01

Full Text Available Denervation of a defined skeletal muscle is due to lower motor neuron (LMN or peripheral nerve lesions that have major consequences on the muscle tissue. After early atrophy, the mid- and late-phases presents two very contrasting myofibers populations: beside those severely atrophic with internalized groups of myonuclei, large fast-type muscle fibers continue to be present 4 to 6 years after Spinal Cord Injury (SCI. Recent results of rat experiments provides the rational basis for understanding the residual functional characteristics of the long-term denervated muscle and the molecular explanation of its ability to respond to home-base functional electrical stimulation (h-b FES using custom-designed electrodes and stimulators. Further outcomes of the Vienna-Padova ten-year collaboration are: 1. a world-unique Myo- Bank of muscle biopsies and 2. improved imaging procedures (Color Computer Tomography (CT scan and Functional Echomyography, all demonstrating that h-b FES induces improvements in muscle contractility, tissue composition and mass, despite permanent LMN denervation. The benefits of h-b FES could be extended from patents suffering with complete Conus-Cauda Syndrome to the numerous patients with incomplete LMN denervation of skeletal muscles to determine whether h-b FES reduces secondary complications related to disuse and impaired blood perfusion (reduction in bone density, risk of bone fracture, decubitus ulcers, and pulmonary thromboembolism. We are confident that translation of the results of a clinical experiment, the EU Project RISE, to the larger cohort of incomplete LMN denervated muscles will provide the wanted results.

Gene Expression Profiling in Slow-Type Calf Soleus Muscle of 30 Days Space-Flown Mice.

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Guido Gambara

Full Text Available Microgravity exposure as well as chronic disuse are two main causes of skeletal muscle atrophy in animals and humans. The antigravity calf soleus is a reference postural muscle to investigate the mechanism of disuse-induced maladaptation and plasticity of human and rodent (rats or mice skeletal musculature. Here, we report microgravity-induced global gene expression changes in space-flown mouse skeletal muscle and the identification of yet unknown disuse susceptible transcripts found in soleus (a mainly slow phenotype but not in extensor digitorum longus (a mainly fast phenotype dorsiflexor as functional counterpart to soleus. Adult C57Bl/N6 male mice (n = 5 flew aboard a biosatellite for 30 days on orbit (BION-M1 mission, 2013, a sex and age-matched cohort were housed in standard vivarium cages (n = 5, or in a replicate flight habitat as ground control (n = 5. Next to disuse atrophy signs (reduced size and myofiber phenotype I to II type shift as much as 680 differentially expressed genes were found in the space-flown soleus, and only 72 in extensor digitorum longus (only 24 genes in common compared to ground controls. Altered expression of gene transcripts matched key biological processes (contractile machinery, calcium homeostasis, muscle development, cell metabolism, inflammatory and oxidative stress response. Some transcripts (Fzd9, Casq2, Kcnma1, Ppara, Myf6 were further validated by quantitative real-time PCR (qRT-PCR. Besides previous reports on other leg muscle types we put forth for the first time a complete set of microgravity susceptible gene transcripts in soleus of mice as promising new biomarkers or targets for optimization of physical countermeasures and rehabilitation protocols to overcome disuse atrophy conditions in different clinical settings, rehabilitation and spaceflight.

Postfatigue potentiation of the paralyzed soleus muscle: evidence for adaptation with long-term electrical stimulation training

OpenAIRE

Shields, Richard K.; Dudley-Javoroski, Shauna; Littmann, Andrew E.

2006-01-01

Understanding the torque output behavior of paralyzed muscle has important implications for the use of functional neuromuscular electrical stimulation systems. Postfatigue potentiation is an augmentation of peak muscle torque during repetitive activation after a fatigue protocol. The purposes of this study were 1) to quantify postfatigue potentiation in the acutely and chronically paralyzed soleus and 2) to determine the effect of long-term soleus electrical stimulation training on the potent...

MRI diagnosis of muscle denervation from herpes zoster with discordant distribution of the skin rash

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Gupta, Amit; Sundaram, Murali [Cleveland Clinic, Section of Musculoskeletal Radiology, Imaging Institute, Cleveland, OH (United States); Winalski, Carl S. [Cleveland Clinic, Section of Musculoskeletal Radiology, Imaging Institute, Cleveland, OH (United States); Cleveland Clinic, Department of Biomedical Engineering, Lerner Research Institute, Cleveland, OH (United States)

2014-10-15

Herpes zoster is a common disorder characterized by a painful rash along a dermatome caused by reactivation of the varicella zoster virus (VZV). Muscle denervation injury from motor involvement is an uncommon phenomenon. Discordant distribution of the skin rash and motor nerve involvement, presenting as a skin rash in one body part and muscle weakness or pain from nerve involvement in another body part is an even more uncommonly reported finding. We present an unusual case of muscle denervation injury resulting from motor involvement of a peripheral nerve by VZV diagnosed by magnetic resonance imaging with cutaneous manifestations in a different dermatomal distribution. To the best of our knowledge, there has been no similar case reported in the English radiology literature. We suggest that whenever a radiologist notices MRI findings suggesting denervation injury and a cause not readily identified, VZV-related denervation injury should be included in the differential diagnosis, especially in an older immunocompromised patient. (orig.)

Action of vanillin (Vanilla planifolia) on the morphology of tibialis anterior and soleus muscles after nerve injury.

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Peretti, Ana Luiza; Antunes, Juliana Sobral; Lovison, Keli; Kunz, Regina Inês; Castor, Lidyane Regina Gomes; Brancalhão, Rose Meire Costa; Bertolini, Gladson Ricardo Flor; Ribeiro, Lucinéia de Fátima Chasko

2017-01-01

To evaluate the action of vanillin (Vanilla planifolia) on the morphology of tibialis anterior and soleus muscles after peripheral nerve injury. Wistar rats were divided into four groups, with seven animals each: Control Group, Vanillin Group, Injury Group, and Injury + Vanillin Group. The Injury Group and the Injury + Vanillin Group animals were submitted to nerve injury by compression of the sciatic nerve; the Vanillin Group and Injury + Vanillin Group, were treated daily with oral doses of vanillin (150mg/kg) from the 3rd to the 21st day after induction of nerve injury. At the end of the experiment, the tibialis anterior and soleus muscles were dissected and processed for light microscopy and submitted to morphological analysis. The nerve compression promoted morphological changes, typical of denervation, and the treatment with vanillin was responsible for different responses in the studied muscles. For the tibialis anterior, there was an increase in the number of satellite cells, central nuclei and fiber atrophy, as well as fascicular disorganization. In the soleus, only increased vascularization was observed, with no exacerbation of the morphological alterations in the fibers. The treatment with vanillin promoted increase in intramuscular vascularization for the muscles studied, with pro-inflammatory potential for tibialis anterior, but not for soleus muscle. Avaliar a ação da vanilina (Vanilla planifolia) sobre a morfologia dos músculos tibial anterior e sóleo após lesão nervosa periférica. Ratos Wistar foram divididos em quatro grupos, com sete animais cada, sendo Grupo Controle, Grupo Vanilina, Grupo Lesão e Grupo Lesão + Vanilina. Os animais dos Grupos Lesão e Grupo Lesão + Vanilina foram submetidos à lesão nervosa por meio da compressão do nervo isquiático, e os Grupos Vanilina e Grupo Lesão + Vanilina foram tratados diariamente com doses orais de vanilina (150mg/kg) do 3o ao 21o dia após a indução da lesão nervosa. Ao término do

Recombinant Uncarboxylated Osteocalcin Per Se Enhances Mouse Skeletal Muscle Glucose Uptake in both Extensor Digitorum Longus and Soleus Muscles

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Xuzhu Lin

2017-11-01

Full Text Available Emerging evidence suggests that undercarboxylated osteocalcin (ucOC improves muscle glucose uptake in rodents. However, whether ucOC can directly increase glucose uptake in both glycolytic and oxidative muscles and the possible mechanisms of action still need further exploration. We tested the hypothesis that ucOC per se stimulates muscle glucose uptake via extracellular signal-regulated kinase (ERK, adenosine monophosphate-activated protein kinase (AMPK, and/or the mechanistic target of rapamycin complex 2 (mTORC2-protein kinase B (AKT-AKT substrate of 160 kDa (AS160 signaling cascade. Extensor digitorum longus (EDL and soleus muscles from male C57BL/6 mice were isolated, divided into halves, and then incubated with ucOC with or without the pretreatment of ERK inhibitor U0126. ucOC increased muscle glucose uptake in both EDL and soleus. It also enhanced phosphorylation of ERK2 (Thr202/Tyr204 and AS160 (Thr642 in both muscle types and increased mTOR phosphorylation (Ser2481 in EDL only. ucOC had no significant effect on the phosphorylation of AMPKα (Thr172. The inhibition of ucOC-induced ERK phosphorylation had limited effect on ucOC-stimulated glucose uptake and AS160 phosphorylation in both muscle types, but appeared to inhibit the elevation in AKT phosphorylation only in EDL. Taken together, ucOC at the physiological range directly increased glucose uptake in both EDL and soleus muscles in mouse. The molecular mechanisms behind this ucOC effect on muscle glucose uptake seem to be muscle type-specific, involving enhanced phosphorylation of AS160 but limitedly modulated by ERK phosphorylation. Our study suggests that, since ucOC increases muscle glucose uptake without insulin, it could be considered as a potential agent to improve muscle glucose uptake in insulin resistant conditions.

Skeletal muscles of hibernating brown bears are unusually resistant to effects of denervation.

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Lin, David C; Hershey, John D; Mattoon, John S; Robbins, Charles T

2012-06-15

Hibernating bears retain most of their skeletal muscle strength despite drastically reduced weight-bearing activity. Regular neural activation of muscles is a potential mechanism by which muscle atrophy could be limited. However, both mechanical loading and neural activity are usually necessary to maintain muscle size. An alternative mechanism is that the signaling pathways related to the regulation of muscle size could be altered so that neither mechanical nor neural inputs are needed for retaining strength. More specifically, we hypothesized that muscles in hibernating bears are resistant to a severe reduction in neural activation. To test this hypothesis, we unilaterally transected the common peroneal nerve, which innervates ankle flexor muscles, in hibernating and summer-active brown bears (Ursus arctos). In hibernating bears, the long digital extensor (LDE) and cranial tibial (CT) musculotendon masses on the denervated side decreased after 11 weeks post-surgery by 18 ± 11 and 25 ± 10%, respectively, compared with those in the intact side. In contrast, decreases in musculotendon masses of summer-active bears after denervation were 61 ± 4 and 58 ± 5% in the LDE and CT, respectively, and significantly different from those of hibernating bears. The decrease due to denervation in summer-active bears was comparable to that occurring in other mammals. Whole-muscle cross-sectional areas (CSAs) measured from ultrasound images and myofiber CSAs measured from biopsies decreased similarly to musculotendon mass. Thus, hibernating bears alter skeletal muscle catabolic pathways regulated by neural activity, and exploration of these pathways may offer potential solutions for disuse atrophy of muscles.

Three-Dimensional Muscle Architecture and Comprehensive Dynamic Properties of Rabbit Gastrocnemius, Plantaris and Soleus: Input for Simulation Studies.

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Siebert, Tobias; Leichsenring, Kay; Rode, Christian; Wick, Carolin; Stutzig, Norman; Schubert, Harald; Blickhan, Reinhard; Böl, Markus

2015-01-01

The vastly increasing number of neuro-muscular simulation studies (with increasing numbers of muscles used per simulation) is in sharp contrast to a narrow database of necessary muscle parameters. Simulation results depend heavily on rough parameter estimates often obtained by scaling of one muscle parameter set. However, in vivo muscles differ in their individual properties and architecture. Here we provide a comprehensive dataset of dynamic (n = 6 per muscle) and geometric (three-dimensional architecture, n = 3 per muscle) muscle properties of the rabbit calf muscles gastrocnemius, plantaris, and soleus. For completeness we provide the dynamic muscle properties for further important shank muscles (flexor digitorum longus, extensor digitorum longus, and tibialis anterior; n = 1 per muscle). Maximum shortening velocity (normalized to optimal fiber length) of the gastrocnemius is about twice that of soleus, while plantaris showed an intermediate value. The force-velocity relation is similar for gastrocnemius and plantaris but is much more bent for the soleus. Although the muscles vary greatly in their three-dimensional architecture their mean pennation angle and normalized force-length relationships are almost similar. Forces of the muscles were enhanced in the isometric phase following stretching and were depressed following shortening compared to the corresponding isometric forces. While the enhancement was independent of the ramp velocity, the depression was inversely related to the ramp velocity. The lowest effect strength for soleus supports the idea that these effects adapt to muscle function. The careful acquisition of typical dynamical parameters (e.g. force-length and force-velocity relations, force elongation relations of passive components), enhancement and depression effects, and 3D muscle architecture of calf muscles provides valuable comprehensive datasets for e.g. simulations with neuro-muscular models, development of more realistic muscle models, or

Three-Dimensional Muscle Architecture and Comprehensive Dynamic Properties of Rabbit Gastrocnemius, Plantaris and Soleus: Input for Simulation Studies.

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Tobias Siebert

Full Text Available The vastly increasing number of neuro-muscular simulation studies (with increasing numbers of muscles used per simulation is in sharp contrast to a narrow database of necessary muscle parameters. Simulation results depend heavily on rough parameter estimates often obtained by scaling of one muscle parameter set. However, in vivo muscles differ in their individual properties and architecture. Here we provide a comprehensive dataset of dynamic (n = 6 per muscle and geometric (three-dimensional architecture, n = 3 per muscle muscle properties of the rabbit calf muscles gastrocnemius, plantaris, and soleus. For completeness we provide the dynamic muscle properties for further important shank muscles (flexor digitorum longus, extensor digitorum longus, and tibialis anterior; n = 1 per muscle. Maximum shortening velocity (normalized to optimal fiber length of the gastrocnemius is about twice that of soleus, while plantaris showed an intermediate value. The force-velocity relation is similar for gastrocnemius and plantaris but is much more bent for the soleus. Although the muscles vary greatly in their three-dimensional architecture their mean pennation angle and normalized force-length relationships are almost similar. Forces of the muscles were enhanced in the isometric phase following stretching and were depressed following shortening compared to the corresponding isometric forces. While the enhancement was independent of the ramp velocity, the depression was inversely related to the ramp velocity. The lowest effect strength for soleus supports the idea that these effects adapt to muscle function. The careful acquisition of typical dynamical parameters (e.g. force-length and force-velocity relations, force elongation relations of passive components, enhancement and depression effects, and 3D muscle architecture of calf muscles provides valuable comprehensive datasets for e.g. simulations with neuro-muscular models, development of more realistic

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.

Effects of muscle activation on shear between human soleus and gastrocnemius muscles.

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Finni, T; Cronin, N J; Mayfield, D; Lichtwark, G A; Cresswell, A G

2017-01-01

Lateral connections between muscles provide pathways for myofascial force transmission. To elucidate whether these pathways have functional roles in vivo, we examined whether activation could alter the shear between the soleus (SOL) and lateral gastrocnemius (LG) muscles. We hypothesized that selective activation of LG would decrease the stretch-induced shear between LG and SOL. Eleven volunteers underwent a series of knee joint manipulations where plantar flexion force, LG, and SOL muscle fascicle lengths and relative displacement of aponeuroses between the muscles were obtained. Data during a passive full range of motion were recorded, followed by 20° knee extension stretches in both passive conditions and with selective electrical stimulation of LG. During active stretch, plantar flexion force was 22% greater (P stronger (stiffer) connectivity between the two muscles, at least at flexed knee joint angles, which may serve to facilitate myofascial force transmission. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Accessory soleus muscle: a case report and review of the literature

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Palaniappan, M. (Leicester Royal Infirmary (United Kingdom). Dept. of Radiology Royal Liverpool Children' s Hospital (United Kingdom). Dept. of Radiology); Rajesh, A.; Rickett, A. (Leicester Royal Infirmary (United Kingdom). Dept. of Radiology); Kershaw, C.J. (Leicester Royal Infirmary (United Kingdom). Dept. of Orthopaedics)

1999-08-01

Accessory soleus muscle is a rare condition which presents as a soft-tissue mass medial to the calcaneum and distal Achilles tendon. Though congenital in origin, it manifests in the second and third decades of life as a soft-tissue mass due to muscle hypertrophy. Patients may be asymptomatic or present with a painful ankle mass. It is important to be aware of this condition when interpreting CT or MRI of the ankle, which show characteristic findings of a normal muscle in an abnormal location. (orig.) With 4 figs., 12 refs.

Deficiency of heat shock transcription factor 1 suppresses heat stress-associated increase in slow soleus muscle mass of mice.

Science.gov (United States)

Ohno, Y; Egawa, T; Yokoyama, S; Nakai, A; Sugiura, T; Ohira, Y; Yoshioka, T; Goto, K

2015-12-01

Effects of heat shock transcription factor 1 (HSF1) deficiency on heat stress-associated increase in slow soleus muscle mass of mice were investigated. Both HSF1-null and wild-type mice were randomly assigned to control and heat-stressed groups. Mice in heat-stressed group were exposed to heat stress (41 °C for 60 min) in an incubator without anaesthesia. Significant increase in wet and dry weights, and protein content of soleus muscle in wild-type mice was observed seven days after the application of the heat stress. However, heat stress had no impact on soleus muscle mass in HSF1-null mice. Neither type of mice exhibited much effect of heat stress on HSF mRNA expression (HSF1, HSF2 and HSF4). On the other hand, heat stress upregulated heat shock proteins (HSPs) at the mRNA (HSP72) and protein (HSP72 and HSP110) levels in wild-type mice, but not in HSF1-null mice. The population of Pax7-positive nuclei relative to total myonuclei of soleus muscle in wild-type mice was significantly increased by heat stress, but not in HSF1-null mice. Furthermore, the absence of HSF1 gene suppressed heat stress-associated phosphorylation of Akt and p70 S6 kinase (p-p70S6K) in soleus muscle. Heat stress-associated increase in skeletal muscle mass may be induced by HSF1 and/or HSF1-mediated stress response that activates muscle satellite cells and Akt/p70S6K signalling pathway. © 2015 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Impaired growth of denervated muscle contributes to contracture formation following neonatal brachial plexus injury.

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Nikolaou, Sia; Peterson, Elizabeth; Kim, Annie; Wylie, Christopher; Cornwall, Roger

2011-03-02

The etiology of shoulder and elbow contractures following neonatal brachial plexus injury is incompletely understood. With use of a mouse model, the current study tests the novel hypothesis that reduced growth of denervated muscle contributes to contractures following neonatal brachial plexus injury. Unilateral brachial plexus injuries were created in neonatal mice by supraclavicular C5-C6 nerve root excision. Shoulder and elbow range of motion was measured four weeks after injury. Fibrosis, cross-sectional area, and functional length of the biceps, brachialis, and subscapularis muscles were measured over four weeks following injury. Muscle satellite cells were cultured from denervated and control biceps muscles to assess myogenic capability. In a comparison group, shoulder motion and subscapularis length were assessed following surgical excision of external rotator muscles. Shoulder internal rotation and elbow flexion contractures developed on the involved side within four weeks following brachial plexus injury. Excision of the biceps and brachialis muscles relieved the elbow flexion contractures. The biceps muscles were histologically fibrotic, whereas fatty infiltration predominated in the brachialis and rotator cuff muscles. The biceps and brachialis muscles displayed reduced cross-sectional and longitudinal growth compared with the contralateral muscles. The upper subscapularis muscle similarly displayed reduced longitudinal growth, with the subscapularis shortening correlating with internal rotation contracture. However, excision of the external rotators without brachial plexus injury caused no contractures or subscapularis shortening. Myogenically capable satellite cells were present in denervated biceps muscles despite impaired muscle growth in vivo. Injury of the upper trunk of the brachial plexus leads to impaired growth of the biceps and brachialis muscles, which are responsible for elbow flexion contractures, and impaired growth of the subscapularis

Hypertrophy Stimulation at the Onset of Type I Diabetes Maintains the Soleus but Not the EDL Muscle Mass in Wistar Rats

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Fortes, Marco A. S.; Scervino, Maria V. M.; Marzuca-Nassr, Gabriel N.; Vitzel, Kaio F.; da Justa Pinheiro, Carlos H.; Curi, Rui

2017-01-01

Diabetes mellitus induces a reduction in skeletal muscle mass and strength. Strength training is prescribed as part of treatment since it improves glycemic control and promotes increase of skeletal muscle mass. The mechanisms involved in overload-induced muscle hypertrophy elicited at the establishment of the type I diabetic state was investigated in Wistar rats. The purpose was to examine whether the overload-induced hypertrophy can counteract the hypotrophy associated to the diabetic state. The experiments were performed in oxidative (soleus) or glycolytic (EDL) muscles. PI3K/Akt/mTOR protein synthesis pathway was evaluated 7 days after overload-induced hypertrophy of soleus and of EDL muscles. The mRNA expression of genes associated with different signaling pathways that control muscle hypertrophy was also evaluated: mechanotransduction (FAK), Wnt/β-catenin, myostatin, and follistatin. The soleus and EDL muscles when submitted to overload had similar hypertrophic responses in control and diabetic animals. The increase of absolute and specific twitch and tetanic forces had the same magnitude as muscle hypertrophic response. Hypertrophy of the EDL muscle from diabetic animals mostly involved mechanical loading-stimulated PI3K/Akt/mTOR pathway besides the reduced activation of AMP-activated protein kinase (AMPK) and decrease of myostatin expression. Hypertrophy was more pronounced in the soleus muscle of diabetic animals due to a more potent activation of rpS6 and increased mRNA expression of insulin-like growth factor-1 (IGF-1), mechano-growth factor (MGF) and follistatin, and decrease of myostatin, MuRF-1 and atrogin-1 contents. The signaling changes enabled the soleus muscle mass and force of the diabetic rats to reach the values of the control group. PMID:29123487

Cold exposure increases slow-type myosin heavy chain 1 (MyHC1) composition of soleus muscle in rats.

Science.gov (United States)

Mizunoya, Wataru; Iwamoto, Yohei; Sato, Yusuke; Tatsumi, Ryuichi; Ikeuchi, Yoshihide

2014-03-01

The aim of this study was to examine the effects of cold exposure on rat skeletal muscle fiber type, according to myosin heavy chain (MyHC) isoform and metabolism-related factors. Male Wistar rats (7 weeks old) were housed individually at 4 ± 2°C as a cold-exposed group or at room temperature (22 ± 2°C) as a control group for 4 weeks. We found that cold exposure significantly increased the slow-type MyHC1 content in the soleus muscle (a typical slow-type fiber), while the intermediate-type MyHC2A content was significantly decreased. In contrast to soleus, MyHC composition of extensor digitorum longus (EDL, a typical fast-type fiber) and gastrocnemius (a mix of slow-type and fast-type fibers) muscle did not change from cold exposure. Cold exposure increased mRNA expression of mitochondrial uncoupling protein 3 (UCP3) in both the soleus and EDL. Cold exposure also increased mRNA expression of myoglobin, peroxisome proliferator-activated receptor gamma coactivator 1α (PGC1α) and forkhead box O1 (FOXO1) in the soleus. Upregulation of UCP3 and PGC1α proteins were observed with Western blotting in the gastrocnemius. Thus, cold exposure increased metabolism-related factors in all muscle types that were tested, but MyHC isoforms changed only in the soleus. © 2013 Japanese Society of Animal Science.

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.

Two weeks of metformin treatment induces AMPK dependent enhancement of insulin-stimulated glucose uptake in mouse soleus muscle

DEFF Research Database (Denmark)

Kristensen, Jonas Møller; Treebak, Jonas Thue; Schjerling, Peter

2014-01-01

signaling. Methods: Oral doses of metformin or saline treatment were given muscle-specific kinase α2 dead AMPK mice (KD) and wild type (WT) littermates either once or chronically for 2 weeks. Soleus and Extensor Digitorum Longus (EDL) muscles were used for measurements of glucose transport and Western blot......Background: Metformin-induced activation of AMPK has been associated with enhanced glucose uptake in skeletal muscle but so far no direct causality has been examined. We hypothesized that an effect of in vivo metformin treatment on glucose uptake in mouse skeletal muscles is dependent upon AMPK...... analyzes. Results: Chronic treatment with metformin enhanced insulin-stimulated glucose uptake in soleus muscles of WT (45%, P...

Hypertrophy Stimulation at the Onset of Type I Diabetes Maintains the Soleus but Not the EDL Muscle Mass in Wistar Rats

Directory of Open Access Journals (Sweden)

Marco A. S. Fortes

2017-10-01

Full Text Available Diabetes mellitus induces a reduction in skeletal muscle mass and strength. Strength training is prescribed as part of treatment since it improves glycemic control and promotes increase of skeletal muscle mass. The mechanisms involved in overload-induced muscle hypertrophy elicited at the establishment of the type I diabetic state was investigated in Wistar rats. The purpose was to examine whether the overload-induced hypertrophy can counteract the hypotrophy associated to the diabetic state. The experiments were performed in oxidative (soleus or glycolytic (EDL muscles. PI3K/Akt/mTOR protein synthesis pathway was evaluated 7 days after overload-induced hypertrophy of soleus and of EDL muscles. The mRNA expression of genes associated with different signaling pathways that control muscle hypertrophy was also evaluated: mechanotransduction (FAK, Wnt/β-catenin, myostatin, and follistatin. The soleus and EDL muscles when submitted to overload had similar hypertrophic responses in control and diabetic animals. The increase of absolute and specific twitch and tetanic forces had the same magnitude as muscle hypertrophic response. Hypertrophy of the EDL muscle from diabetic animals mostly involved mechanical loading-stimulated PI3K/Akt/mTOR pathway besides the reduced activation of AMP-activated protein kinase (AMPK and decrease of myostatin expression. Hypertrophy was more pronounced in the soleus muscle of diabetic animals due to a more potent activation of rpS6 and increased mRNA expression of insulin-like growth factor-1 (IGF-1, mechano-growth factor (MGF and follistatin, and decrease of myostatin, MuRF-1 and atrogin-1 contents. The signaling changes enabled the soleus muscle mass and force of the diabetic rats to reach the values of the control group.

Hypothyroidism in the rat results in decreased soleus motoneurone soma size

NARCIS (Netherlands)

Bakels, R; Nijenhuis, Albertine; Mast, L; Kernell, D

1998-01-01

Adult female rats were thyroidectomized. After an average of 17 weeks, horseradish peroxidase (HRP) was injected into the right side soleus muscle. Two days later, left side soleus muscle properties were recorded and muscles and spinal cord were removed for further histological measurements. Soleus

Diffusion tensor imaging and T2 mapping in early denervated skeletal muscle in rats.

Science.gov (United States)

Ha, Dong-Ho; Choi, Sunseob; Kang, Eun-Ju; Park, Hwan Tae

2015-09-01

To evaluate the temporal changes of diffusion tensor imaging (DTI) indices, T2 values, and visual signal intensity on various fat suppression techniques in the early state of denervated skeletal muscle in a rat model. Institutional Animal Care and Use Committee approval was obtained. Sciatic nerves of eight rats were transected for irreversible neurotmesis model. We examined normal lower leg and denervated muscles at 3 days, 1 week, and 2 weeks on a 3 Tesla MR. fractional anisotropy (FA), mean apparent diffusion coefficient (mADC), and T2 values were measured by using DTI and T2 mapping scan. We subjectively classified the signal intensity change on various fat suppression images into the following three grades: negative, suspicious, and definite change. Wilcoxon-sign rank test and Kruskal-Wallis test were used for the comparison of FA, mADC, T2 values. McNemar's test was used for comparing signal intensity change among fat suppression techniques. FA values of denervated muscles at 3 days (0.35 ± 0.06), 1 week (0.29 ± 0.04), and 2 weeks (0.34 ± 0.05) were significantly (P  0.05) change. T2 values were significantly increased at 1 week (38.11 ± 6.42 ms, P = 0.017) and markedly increased at 2 weeks (46.53 ± 5.17 ms, P = 0.012). The grade of visual signal intensity change on chemical shift selective fat saturation, STIR and IDEAL images were identical in all cases (P = 1.000). FA and T2 values can demonstrate the early temporal changes in denervated rat skeletal muscle. © 2014 Wiley Periodicals, Inc.

Two weeks of metformin treatment induces AMPK-dependent enhancement of insulin-stimulated glucose uptake in mouse soleus muscle

Science.gov (United States)

Kristensen, Jonas Møller; Treebak, Jonas T.; Schjerling, Peter; Goodyear, Laurie

2014-01-01

Metformin-induced activation of the 5′-AMP-activated protein kinase (AMPK) has been associated with enhanced glucose uptake in skeletal muscle, but so far no direct causality has been examined. We hypothesized that an effect of in vivo metformin treatment on glucose uptake in mouse skeletal muscles is dependent on AMPK signaling. Oral doses of metformin or saline treatment were given to muscle-specific kinase dead (KD) AMPKα2 mice and wild-type (WT) littermates either once or chronically for 2 wk. Soleus and extensor digitorum longus muscles were used for measurements of glucose transport and Western blot analyses. Chronic treatment with metformin enhanced insulin-stimulated glucose uptake in soleus muscles of WT (∼45%, P metformin treatment. Insulin signaling at the level of Akt and TBC1D4 protein expression as well as Akt Thr308/Ser473 and TBC1D4 Thr642/Ser711 phosphorylation were not changed by metformin treatment. Also, protein expressions of Rab4, GLUT4, and hexokinase II were unaltered after treatment. The acute metformin treatment did not affect glucose uptake in muscle of either of the genotypes. In conclusion, we provide novel evidence for a role of AMPK in potentiating the effect of insulin on glucose uptake in soleus muscle in response to chronic metformin treatment. PMID:24644243

Intracellular uptake and degradation of extracellular tracers in mouse skeletal muscle in vitro: the effect of denervation

International Nuclear Information System (INIS)

Libelius, R.; Lundquist, I.; Templeton, W.; Thesleff, S.

1978-01-01

Innervated and chronically denervated mouse skeletal muscles have been incubated under various conditions in a Ringer solution containing one of the three macromolecules [ 3 H] α-neurotoxin, [ 3 H]inulin and horseradish peroxidase. Following extensive wash-out for 4 h of the extracellular compartment, the amount of each macromolecule retained intracellularly was obtained. Intracellular uptake of a [ 3 H]monoacetylated α-neurotoxin in vitro at 37 C was found to be increased in denervated mouse extensor digitorum longus muscles compared to innervated control muscles. Similarly, the uptake in vitro at 37 C of [ 3 H] inulin and horseradish peroxidase was also increased in denervated muscles. At 4 C the uptake of [ 3 H]inulin and horseradish peroxidase was markedly reduced. Protamine was found to stimulate the uptake of [ 3 H]inulin at 37 C, but not at 4 C. Reduction in specific activity by addition of 50-fold excess of unlabelled inulin failed to affect the uptake of [ 3 H]inulin suggesting that this uptake process obeyed bulk kinetics. Furthermore, the endocytized [ 3 H]inulin was found to be strongly retained in the muscles since prolonged washing or addition of unlabelled inulin to the washing solution did not reduce the uptake. Characterization of [ 3 H]inulin taken up by the muscles was performed by gel chromatography on Sephadex G-25. Using a purified [ 3 H]inulin solution it was observed that about 45% of the total radioactivity remaining in the muscles was eluted as [ 3 H]inulin. Additional radioactivity consisted of lower molecular weight compounds. These degradation products of [ 3 H]inulin were only present in the muscle homogenate and were not detected in the incubation solution. The results suggest that intracellular uptake of different macromolecules by endocytosis in skeletal muscles increases following denervation, and that following uptake, degradation of the endocytized material may occur. (author)

Improved neurological outcome by intramuscular injection of human amniotic fluid derived stem cells in a muscle denervation model.

Directory of Open Access Journals (Sweden)

Chun-Jung Chen

Full Text Available The skeletal muscle develops various degrees of atrophy and metabolic dysfunction following nerve injury. Neurotrophic factors are essential for muscle regeneration. Human amniotic fluid derived stem cells (AFS have the potential to secrete various neurotrophic factors necessary for nerve regeneration. In the present study, we assess the outcome of neurological function by intramuscular injection of AFS in a muscle denervation and nerve anastomosis model.Seventy two Sprague-Dawley rats weighing 200-250 gm were enrolled in this study. Muscle denervation model was conducted by transverse resection of a sciatic nerve with the proximal end sutured into the gluteal muscle. The nerve anastomosis model was performed by transverse resection of the sciatic nerve followed by four stitches reconnection. These animals were allocated to three groups: control, electrical muscle stimulation, and AFS groups.NT-3 (Neurotrophin 3, BDNF (Brain derived neurotrophic factor, CNTF (Ciliary neurotrophic factor, and GDNF (Glia cell line derived neurotrophic factor were highly expressed in AFS cells and supernatant of culture medium. Intra-muscular injection of AFS exerted significant expression of several neurotrophic factors over the distal end of nerve and denervated muscle. AFS caused high expression of Bcl-2 in denervated muscle with a reciprocal decrease of Bad and Bax. AFS preserved the muscle morphology with high expression of desmin and acetylcholine receptors. Up to two months, AFS produced significant improvement in electrophysiological study and neurological functions such as SFI (sciatic nerve function index and Catwalk gait analysis. There was also significant preservation of the number of anterior horn cells and increased nerve myelination as well as muscle morphology.Intramuscular injection of AFS can protect muscle apoptosis and likely does so through the secretion of various neurotrophic factors. This protection furthermore improves the nerve

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

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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.

Locomotor adaptation to a soleus EMG-controlled antagonistic exoskeleton.

Science.gov (United States)

Gordon, Keith E; Kinnaird, Catherine R; Ferris, Daniel P

2013-04-01

Locomotor adaptation in humans is not well understood. To provide insight into the neural reorganization that occurs following a significant disruption to one's learned neuromuscular map relating a given motor command to its resulting muscular action, we tied the mechanical action of a robotic exoskeleton to the electromyography (EMG) profile of the soleus muscle during walking. The powered exoskeleton produced an ankle dorsiflexion torque proportional to soleus muscle recruitment thus limiting the soleus' plantar flexion torque capability. We hypothesized that neurologically intact subjects would alter muscle activation patterns in response to the antagonistic exoskeleton by decreasing soleus recruitment. Subjects practiced walking with the exoskeleton for two 30-min sessions. The initial response to the perturbation was to "fight" the resistive exoskeleton by increasing soleus activation. By the end of training, subjects had significantly reduced soleus recruitment resulting in a gait pattern with almost no ankle push-off. In addition, there was a trend for subjects to reduce gastrocnemius recruitment in proportion to the soleus even though only the soleus EMG was used to control the exoskeleton. The results from this study demonstrate the ability of the nervous system to recalibrate locomotor output in response to substantial changes in the mechanical output of the soleus muscle and associated sensory feedback. This study provides further evidence that the human locomotor system of intact individuals is highly flexible and able to adapt to achieve effective locomotion in response to a broad range of neuromuscular perturbations.

Locomotor adaptation to a soleus EMG-controlled antagonistic exoskeleton

Science.gov (United States)

Kinnaird, Catherine R.; Ferris, Daniel P.

2013-01-01

Locomotor adaptation in humans is not well understood. To provide insight into the neural reorganization that occurs following a significant disruption to one's learned neuromuscular map relating a given motor command to its resulting muscular action, we tied the mechanical action of a robotic exoskeleton to the electromyography (EMG) profile of the soleus muscle during walking. The powered exoskeleton produced an ankle dorsiflexion torque proportional to soleus muscle recruitment thus limiting the soleus' plantar flexion torque capability. We hypothesized that neurologically intact subjects would alter muscle activation patterns in response to the antagonistic exoskeleton by decreasing soleus recruitment. Subjects practiced walking with the exoskeleton for two 30-min sessions. The initial response to the perturbation was to “fight” the resistive exoskeleton by increasing soleus activation. By the end of training, subjects had significantly reduced soleus recruitment resulting in a gait pattern with almost no ankle push-off. In addition, there was a trend for subjects to reduce gastrocnemius recruitment in proportion to the soleus even though only the soleus EMG was used to control the exoskeleton. The results from this study demonstrate the ability of the nervous system to recalibrate locomotor output in response to substantial changes in the mechanical output of the soleus muscle and associated sensory feedback. This study provides further evidence that the human locomotor system of intact individuals is highly flexible and able to adapt to achieve effective locomotion in response to a broad range of neuromuscular perturbations. PMID:23307949

[Jejunal myenteric denervation induced by benzalkonium chloride].

Science.gov (United States)

Ramalho, F S; Santos, G C; Ramalho, L N; Kajiwara, J K; Zucoloto, S

1994-01-01

The effects of benzalkonium chloride (BAC) on the number of myenteric neurons, muscle thickness and external perimeter after acute (until 10 days after BAC application) and chronic (30 and 60 days after BAC application) denervation of the proximal jejunum were determined in rats. There was a significant reduction in the number of myenteric neurons of all segments treated with BAC. The extent of denervation varied along the time, and it was reduced in the denervated segments of the chronic group in comparison with the acute group. This may be due to the neuroplasticity phenomenon appearing during the chronic phase. Myenteric denervation increased the thickness of the propria muscle layer, especially in the longitudinal muscle layer, suggesting a higher sensitivity of this layer to myenteric denervation.

Major alteration of the pathological phenotype in gamma irradiated mdx soleus muscles

Energy Technology Data Exchange (ETDEWEB)

Weller, B.; Karpati, G.; Lehnert, S.; Carpenter, S. (Montreal Neurological Institute, McGill University, Quebec (Canada))

1991-07-01

Two thousand rads of gamma irradiation delivered to the lower legs of ten day old normal and x-chromosome linked muscular dystrophy (mdx) mice caused significant inhibition of tibial bone and soleus muscle fiber growth. In the irradiated mdx solei, there was a major loss of muscle fibers, lack of central nucleation, and some endomysial fibrosis. These features were caused by a failure of regeneration of muscle fibers due to impaired proliferative capacity of satellite cells. Gamma irradiation transforms the late pathological phenotype of mdx muscles, so that in one major aspect (muscle fiber loss) they resemble muscles in Duchenne muscular dystrophy. However, extensive endomysial fibrosis which is another characteristic feature of Duchenne muscular dystrophy did not develop. This experimental model could be useful for the functional investigation of possible beneficial effects of therapeutic interventions in mdx dystrophy.

Major alteration of the pathological phenotype in gamma irradiated mdx soleus muscles

International Nuclear Information System (INIS)

Weller, B.; Karpati, G.; Lehnert, S.; Carpenter, S.

1991-01-01

Two thousand rads of gamma irradiation delivered to the lower legs of ten day old normal and x-chromosome linked muscular dystrophy (mdx) mice caused significant inhibition of tibial bone and soleus muscle fiber growth. In the irradiated mdx solei, there was a major loss of muscle fibers, lack of central nucleation, and some endomysial fibrosis. These features were caused by a failure of regeneration of muscle fibers due to impaired proliferative capacity of satellite cells. Gamma irradiation transforms the late pathological phenotype of mdx muscles, so that in one major aspect (muscle fiber loss) they resemble muscles in Duchenne muscular dystrophy. However, extensive endomysial fibrosis which is another characteristic feature of Duchenne muscular dystrophy did not develop. This experimental model could be useful for the functional investigation of possible beneficial effects of therapeutic interventions in mdx dystrophy

Intracellular uptake and degradation of extracellular tracers in mouse skeletal muscle in vitro: the effect of denervation

Energy Technology Data Exchange (ETDEWEB)

Libelius, R; Lundquist, I; Templeton, W; Thesleff, S [Lund Univ. (Sweden)

1978-01-01

Innervated and chronically denervated mouse skeletal muscles have been incubated under various conditions in a Ringer solution containing one of the three macromolecules (/sup 3/H) ..cap alpha..-neurotoxin, (/sup 3/H)inulin and horseradish peroxidase. Following extensive wash-out for 4 h of the extracellular compartment, the amount of each macromolecule retained intracellularly was obtained. Intracellular uptake of a (/sup 3/H)monoacetylated ..cap alpha..-neurotoxin in vitro at 37 C was found to be increased in denervated mouse extensor digitorum longus muscles compared to innervated control muscles. Similarly, the uptake in vitro at 37 C of (/sup 3/H) inulin and horseradish peroxidase was also increased in denervated muscles. At 4 C the uptake of (/sup 3/H)inulin and horseradish peroxidase was markedly reduced. Protamine was found to stimulate the uptake of (/sup 3/H)inulin at 37 C, but not at 4 C. Reduction in specific activity by addition of 50-fold excess of unlabelled inulin failed to affect the uptake of (/sup 3/H)inulin suggesting that this uptake process obeyed bulk kinetics. Furthermore, the endocytized (/sup 3/H)inulin was found to be strongly retained in the muscles since prolonged washing or addition of unlabelled inulin to the washing solution did not reduce the uptake. Characterization of (/sup 3/H)inulin taken up by the muscles was performed by gel chromatography on Sephadex G-25. Using a purified (/sup 3/H)inulin solution it was observed that about 45% of the total radioactivity remaining in the muscles was eluted as (/sup 3/H)inulin. Additional radioactivity consisted of lower molecular weight compounds. Degradation products of (/sup 3/H)inulin were only present in the muscle homogenate and were not detected in the incubation solution. Results suggest that intracellular uptake of different macromolecules by endocytosis in skeletal muscles increases following denervation, and that following uptake, degradation of the endocytized material may occur.

Comparison between neurectomy and botulinum toxin A injection for denervated skeletal muscle.

Science.gov (United States)

Tsai, Feng-Chou; Hsieh, Ming-Shium; Chou, Chih-Ming

2010-08-01

Neurectomy and botulinum toxin A (BoNT-A) injection cause denervated muscle atrophy, but questions remain about their clinical utility. We investigated time-series alterations of rat muscle weight, functional deficits, signaling pathways, and microscopic structures, to gain an understanding of the clinical implications. Between 2008 and 2009, the maximal calf circumference of patients for calf reduction either by neurectomy or BoNT-A injections were recorded for study. A rat skeletal muscle model was established through repeated or dose-adjusted BoNT-A injections and neurectomy. The survival, apoptosis pathways, functional deficits, and microscopic structures were investigated using Western blot, sciatic functional index (SFI), and transmission electron microscopy (TEM), respectively. The rat muscle weight ratio of the BoNT-A group had recovered to 89.3 +/- 3.8% by week 58, but it never recovered in the neurectomy group. Muscle weight reduction by BoNT-A not only depended on the dose, but additive effects were also obtained through repeated injections. Rat SFI demonstrated rapid recovery in both groups. Molecular expressions showed a coherent and biphasic pattern. p-Akt and apoptosis-inducing factor (AIF) were upregulated significantly, with a peak at 8 weeks in the neurectomy group (p structure disruption and sarcomere discontinuity in the neurectomy and BoNT-A groups, respectively. We demonstrated that denervation induced lasting muscle weight and structural changes of different degrees. Muscle weight reduction by BoNT-A was related to frequency and dose. AIF-mediated caspase-independent apoptosis was significantly different for neurectomy and BoNT-A injection.

β-adrenergic ([3H] CGP-12177) receptors are elevated in slices of soleus muscle from CHF 147 dystrophic hamsters

International Nuclear Information System (INIS)

Watson-Wright, W.M.; Wilkinson, M.

1987-01-01

The authors utilized a muscle slice technique to compare the ontogeny of cell surface β-adrenergic receptor binding in soleus and extensor digitorum longus (EDL) muscles of male Golden Syrian (GS) and Canadian Hybrid Farms 147 (CHF 147) dystrophic hamsters. Binding of the β-adrenergic antagonist, [ 3 H] CGP-12177 (CGP), to GS muscle slices was reversible, saturable, stereospecific and of high affinity. Bmax was higher in the soleus (2.57+/-.12 fmol/mg wet wt) than in the EDL (1.61+/-.17 fmol/mg wet wt) of adult animals while affinities were similar (0.35+/-.06 and 0.24+/-.04 nM respectively). No differences in binding characteristics were seen in EDL of GS compared to CHF 147 animals. In soleus slices from GS hamsters, Bmax was highest at 16 days of age (5.72+/-0.26 fmol/mg), decreased between 16 and 29 days and remained constant until 300 days (2.51+/-0.52 fmol/mg). In dystrophic soleus slices, Bmax was also higher at 16 days than at any other age but receptor number decreased gradually, remaining higher than in GS until 90 days of age (p<0.05). The failure of β-adrenergic receptor number to decrease at a normal rate may be implicated in the pathogenesis of hamster polymyopathy. 21 references, 5 figures, 1 table

Metabolic stabilization of acetylcholine receptors in vertebrate neuromuscular junction by muscle activity

International Nuclear Information System (INIS)

Rotzler, S.; Brenner, H.R.

1990-01-01

The effects of muscle activity on the growth of synaptic acetylcholine receptor (AChR) accumulations and on the metabolic AChR stability were investigated in rat skeletal muscle. Ectopic end plates induced surgically in adult soleus muscle were denervated early during development when junctional AChR number and stability were still low and, subsequently, muscles were either left inactive or they were kept active by chronic exogenous stimulation. AChR numbers per ectopic AChR cluster and AChR stabilities were estimated from the radioactivity and its decay with time, respectively, of end plate sites whose AChRs had been labeled with 125 I-alpha-bungarotoxin (alpha-butx). The results show that the metabolic stability of the AChRs in ectopic clusters is reversibly increased by muscle activity even when innervation is eliminated very early in development. 1 d of stimulation is sufficient to stabilize the AChRs in ectopic AChR clusters. Muscle stimulation also produced an increase in the number of AChRs at early denervated end plates. Activity-induced cluster growth occurs mainly by an increase in area rather than in AChR density, and for at least 10 d after denervation is comparable to that in normally developing ectopic end plates. The possible involvement of AChR stabilization in end plate growth is discussed

In Vivo Real-Time Imaging of Exogenous HGF-Triggered Cell Migration in Rat Intact Soleus Muscles

International Nuclear Information System (INIS)

Ishido, Minenori; Kasuga, Norikatsu

2012-01-01

The transplantation of myogenic cells is a potentially effective therapy for muscular dystrophy. However, this therapy has achieved little success because the diffusion of transplanted myogenic cells is limited. Hepatocyte growth factor (HGF) is one of the primary triggers to induce myogenic cell migration in vitro. However, to our knowledge, whether exogenous HGF can trigger the migration of myogenic cells (i.e. satellite cells) in intact skeletal muscles in vivo has not been reported. We previously reported a novel in vivo real-time imaging method in rat skeletal muscles. Therefore, the present study examined the relationship between exogenous HGF treatment and cell migration in rat intact soleus muscles using this imaging method. As a result, it was indicated that the cell migration velocity was enhanced in response to increasing exogenous HGF concentration in skeletal muscles. Furthermore, the expression of MyoD was induced in satellite cells in response to HGF treatment. We first demonstrated in vivo real-time imaging of cell migration triggered by exogenous HGF in intact soleus muscles. The experimental method used in the present study will be a useful tool to understand further the regulatory mechanism of HGF-induced satellite cell migration in skeletal muscles in vivo

Afferent-mediated modulation of the soleus muscle activity during the stance phase of human walking

DEFF Research Database (Denmark)

Nazarena, Mazzaro; Grey, Michael James; do Nascimento, Omar Feix

2006-01-01

The aim of this study was to investigate the contribution of proprioceptive feedback to the amplitude modulation of the soleus muscle activity during human walking. We have previously shown that slow-velocity, small-amplitude ankle dorsiflexion enhancements and reductions applied during the stance...

Modulation of the Neuregulin 1/ErbB system after skeletal muscle denervation and reinnervation.

Science.gov (United States)

Morano, Michela; Ronchi, Giulia; Nicolò, Valentina; Fornasari, Benedetta Elena; Crosio, Alessandro; Perroteau, Isabelle; Geuna, Stefano; Gambarotta, Giovanna; Raimondo, Stefania

2018-03-22

Neuregulin 1 (NRG1) is a growth factor produced by both peripheral nerves and skeletal muscle. In muscle, it regulates neuromuscular junction gene expression, acetylcholine receptor number, muscle homeostasis and satellite cell survival. NRG1 signalling is mediated by the tyrosine kinase receptors ErbB3 and ErbB4 and their co-receptors ErbB1 and ErbB2. The NRG1/ErbB system is well studied in nerve tissue after injury, but little is known about this system in skeletal muscle after denervation/reinnervation processes. Here, we performed a detailed time-course expression analysis of several NRG1 isoforms and ErbB receptors in the rat superficial digitorum flexor muscle after three types of median nerve injuries of different severities. We found that ErbB receptor expression was correlated with the innervated state of the muscle, with upregulation of ErbB2 clearly associated with the denervation state. Interestingly, the NRG1 isoforms were differently regulated depending on the nerve injury type, leading to the hypothesis that both the NRG1α and NRG1β isoforms play a key role in the muscle reaction to injury. Indeed, in vitro experiments with C2C12 atrophic myotubes revealed that both NRG1α and NRG1β treatment influences the best-known atrophic pathways, suggesting that NRG1 might play an anti-atrophic role.

Capillarity, oxidative capacity and fibre composition of the soleus and gastrocnemius muscles of rats in hypothyroidism.

Science.gov (United States)

Sillau, A H

1985-01-01

Muscle capillarity, mean and maximal diffusion distances and muscle fibre composition were evaluated in frozen sections stained for myosin ATPase of the soleus and the white area of the gastrocnemius medial head (gastrocnemius) of rats made hypothyroid by the injection of propylthiouracil (PTU) (50 mg kg-1) every day for 21 or 42 days. Oxygen consumption in the presence of excess ADP and Pi with pyruvate plus malate as substrates and the activity of cytochrome c oxidase were measured in muscle homogenates. Treatment with PTU decreased body oxygen consumption and the concentration of triiodothyronine in plasma. The capacity of the soleus and gastrocnemius muscles' homogenates to oxidize pyruvate plus malate and their cytochrome c oxidase activity were reduced after 21 or 42 days of treatment with PTU. Fibre composition in the soleus muscle was changed by treatment with PTU. There was a decrease in the proportion of type IIa or fast glycolytic oxidative fibres and an increase in type I or slow oxidative fibres. After 21 days of PTU administration there was also an increase in the proportion of fibres classified as IIc. The changes in fibre composition are believed to be the result of changes in the types of myosin synthesized by the fibres. Therefore, the fibres classified as IIc are, most probably, IIa fibres in the process of changing their myosin to that of the type I fibres. No changes in fibre composition were evident in the white area of the gastrocnemius medial head, an area made up of IIb or fast glycolytic fibres. The indices of capillarity: capillary density and capillary to fibre ratio, as well as mean and maximal diffusion distances from the capillaries, were not changed by the treatment with PTU in the muscles studied. The lack of changes in capillarity in spite of significant changes in oxidative capacity indicates that in skeletal muscle capillarity is not necessarily related to the oxidative capacity of the fibres. PMID:3989729

Fibre type composition of soleus and extensor digitorum longus muscles in normal female inbred Lewis rats

Czech Academy of Sciences Publication Activity Database

Soukup, Tomáš; Zachařová, Gisela; Smerdu, V.

2002-01-01

Roč. 104, č. 4 (2002), s. 399-405 ISSN 0065-1281 R&D Projects: GA ČR GA304/00/1653 Grant - others:CZ - SI Czech-Slovenian Intergovernmental S&T Co-operation(XC) - Institutional research plan: CEZ:AV0Z5011922 Keywords : inbred Lewis rats * skeletal muscles * soleus and EDL muscles Subject RIV: FH - Neurology Impact factor: 0.867, year: 2002

Myostatin dysfunction impairs force generation in extensor digitorum longus muscle and increases exercise-induced protein efflux from extensor digitorum longus and soleus muscles.

Science.gov (United States)

Baltusnikas, Juozas; Kilikevicius, Audrius; Venckunas, Tomas; Fokin, Andrej; Bünger, Lutz; Lionikas, Arimantas; Ratkevicius, Aivaras

2015-08-01

Myostatin dysfunction promotes muscle hypertrophy, which can complicate assessment of muscle properties. We examined force generating capacity and creatine kinase (CK) efflux from skeletal muscles of young mice before they reach adult body and muscle size. Isolated soleus (SOL) and extensor digitorum longus (EDL) muscles of Berlin high (BEH) mice with dysfunctional myostatin, i.e., homozygous for inactivating myostatin mutation, and with a wild-type myostatin (BEH+/+) were studied. The muscles of BEH mice showed faster (P myostatin dysfunction leads to impairment in muscle force generating capacity in EDL and increases susceptibility of SOL and EDL to protein loss after exercise.

Oedema and fatty degeneration of the soleus and gastrocnemius muscles on MR images in patients with achilles tendon abnormalities

International Nuclear Information System (INIS)

Hoffmann, Adrienne; Mamisch, Nadja; Buck, Florian M.; Pfirrmann, Christian W.A.; Zanetti, Marco; Espinosa, Norman

2011-01-01

The purpose of this study was to evaluate the frequency of oedema and fatty degeneration of the soleus and gastrocnemius muscles in patients with Achilles tendon abnormalities. Forty-five consecutive patients (mean 51 years; range 14-84 years) with achillodynia were examined with magnetic resonance (MR) images of the calf. The frequency of oedema and fatty degeneration in the soleus and gastrocnemius muscles was determined in patients with normal tendons, tendinopathy and in patients with a partial tear or a complete tear of the Achilles tendon. Oedema was encountered in 35% (7/20) of the patients with tendinopathy (n = 20; range 13-81 years), and in 47% (9/19) of the patients with partial tears or complete tears (n = 19; 28-78 years). Fatty degeneration was encountered in 10% (2/20) of the patients with tendinopathy, and in 32% (6/19) of the patients with tears. The prevalence of fatty degeneration was significantly more common in patients with a partial or complete tear compared with the patients with a normal Achilles tendon (p = 0.032 and p = 0.021, respectively). Oedema and fatty degeneration of the soleus and gastrocnemius muscles are common in patients with Achilles tendon abnormalities. (orig.)

3D Modelling and monitoring of denervated muscle under Functional Electrical Stimulation treatment and associated bone structural changes

Directory of Open Access Journals (Sweden)

Paolo Gargiulo

2011-03-01

Full Text Available A novel clinical rehabilitation method for patients who have permanent and non recoverable muscle denervation in the legs was developed in the frame of the European Project RISE. The technique is based on FES and the project results shows, in these severely disabled patients, restoration of muscle tissue and function. This study propose novel methods based on image processing technique and medical modelling to monitor growth in denervated muscle treated with FES. Geometrical and structural changes in muscle and bone are studied and modelled. Secondary effects on the bone mineral density produced by the stimulation treatment and due the elicited muscle contraction are also investigated. The restoration process in DDM is an important object of discussion since there isn’t yet a complete understanding of the mechanisms regulating growth in denervated muscle. This study approaches the problem from a macroscopic point of view, developing 3-dimensional models of the whole stimulated muscles and following changes in volume, geometry and density very accurately. The method is based on the acquisition of high resolution Spiral CT scans from patients who have long-term flaccid paraplegia and the use of special image processing tools allowing tissue discriminations and muscle segmentation. Three patients were measured at different points of time during 4 years of electrical stimulation treatment. In this study is quantitatively demonstrated the influences of FES treatment on the different quadriceps bellies. The rectus femoris muscle is positioned in the middle of the quadriceps and responds (in general better to stimulation. In a patient with abundant adipose tissue surrounding the quadriceps, rectus femoris almost doubled the volume during the FES treatment while in the other bellies the changes measured were minimal. The analysis of the density shows clearly a restoration of the muscular structure in the growing muscle. The remarkable increase of

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

Neurogenic myopathies and imaging of muscle denervation; Neurogene Myopathien und Bildgebung der Muskeldenervation

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Wolf, M. [Universitaetsklinikum Heidelberg, Abteilung fuer Neuroradiologie, Heidelberg (Germany); Wolf, C. [Reha-Zentrum Gernsbach, Neurologie, Gernsbach (Germany); Weber, M.A. [Universitaetsklinikum Heidelberg, Abteilung fuer Diagnostische und Interventionelle Radiologie, Heidelberg (Germany)

2017-12-15

Neurogenic myopathies are primary diseases of the nervous system, which secondarily result in denervation of the target musculature. The spectrum of potential causes is manifold ranging from acute traumatic injuries and chronic compression to neurodegenerative, inflammatory, metabolic and neoplastic processes. The medical history, clinical neurological examination, and electrophysiological tests including electromyography and nerve conduction studies are crucial in diagnosing neuropathic myopathies. Electromyography is the gold standard for diagnosing muscle denervation. Additional imaging methods and magnetic resonance imaging (MRI) in particular, are capable of contributing valuable information. The MRI examination of denervated musculature shows edema, an increase in the apparent diffusion coefficient (ADC) and hyperperfusion. Chronic denervation results in fatty degeneration and atrophy of affected muscles, which are also detectable by MRI. Although the MRI findings in muscle denervation are relatively unspecific, they show a high sensitivity, comparable to electromyography. Dedicated MR neurography may often visualize the underlying lesion(s) of the innervating nerve(s). Besides high sensitivity, comparable to electromyography, MRI is capable of evaluating muscles which are inaccessible for needle electromyography. Due to its non-invasive character, MRI is ideal for follow-up examinations. The use of MRI is often a meaningful addition to the diagnostics of neurogenic myopathies. The extent and distribution pattern of muscular alterations often provide information on the localization of the causative nerve damage. A correct diagnosis or at least a narrowing down of possible differential diagnoses can often be achieved using MRI. (orig.) [German] Neurogene Myopathien sind Erkrankungen des Nervensystems, die sekundaer zur Denervierung der Zielmuskulatur fuehren. Das Spektrum potenzieller Ursachen ist vielfaeltig und umfasst akute traumatische Verletzungen

The effects of beta-adrenoceptor activation on contraction in isolated fast- and slow-twitch skeletal muscle fibres of the rat.

OpenAIRE

Cairns, S. P.; Dulhunty, A. F.

1993-01-01

1. The aim of the experiments was to examined the effects of beta-adrenoceptor activation on twitch and tetanic contractions in fast- and slow-twitch mammalian skeletal muscle fibres. Isometric force was recorded from bundles of intact fibres isolated from the normal and denervated slow-twitch soleus and normal fast-twitch sternomastoid muscles of the rat. 2. Terbutaline (10 microM), a beta 2-adrenoceptor agonist, induced an average 15% potentiation of peak twitch and peak tetanic force in no...

Isoform-specific changes in the Na,K-ATPase of rat soleus muscle during acute hindlinb suspension

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Krivoi, Igor; Heiny, Judith; Bouzinova, Elena; Matchkov, Vladimir; Kravtsova, Violetta; Petrov, Aleksey; Zefirov, Andrey; Vasiliev, Alexander

The largest pool of Na,K-ATPase (NKA) in a vertebrate's body is contained in the skeletal muscles where the alpha1 and alpha2 isoforms of NKA alpha subunit are expressed. The NKA is critically important for excitability, electrogenesis and contractility of skeletal muscle. Skeletal muscle use strongly regulates the content of NKA, and increased muscle activity differently regulates the alpha1 and alpha2 isoforms. However, whether skeletal muscle disuse affects NKA content and activity has not been investigated. This study examines for the first time the consequences of acute hindlinb suspension (HS) on the alpha1 and alpha2 NKA isozymes in rat soleus muscle. We subjected rats to HS for 6-12 hours and analyzed its effect on the resting membrane potential (RMP) in different sarcolemma regions of m.soleus fibers; the electrogenic transport activity, protein content and mRNA expression of the alpha1 and alpha2 NKA; the extracellular level of acetylcholine, and the plasma membrane localization of the alpha2 isozyme using confocal microscopy with cytochemistry. Our results show that 6 h HS specifically decreases the electrogenic activity of the NKA alpha2 isozyme and depolarizes m.soleus fibers. These effects are irreversible in the extrajunctional membrane region up to 12 h HS. The decreased alpha2 NKA activity is due to a decrease in enzyme activity rather than by altered protein content, mRNA expression, or localization in the sarcolemma. In addition, HS does not alter the alpha2 NKA electrogenic transport due to decreased extracellular acetylcholine level. However, adaptive mechanism(s) operate at the junctional membrane to restore alpha2 NKA electrogenic activities and the RMP after 12 h of HS. This mechanism operates specifically at the synaptic membrane region, presumably via increase in both alpha2 isozyme mRNA expression and protein content. This basic information on a protein as vital as the NKA is expected to advance our understanding of the cellular and

Glycogen supercompensation in rat soleus muscle during recovery from nonweight bearing

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Henriksen, Erik J.; Kirby, Christopher R.; Tischler, Marc E.

1989-01-01

Events leading to the normalization of the glycogen metabolism in the soleus muscle of rat, altered by 72-h three days of hind-limb suspension, were investigated during the 72-h recovery period when the animals were allowed to bear weight on all four limbs. Relative importance of the factors affecting glycogen metabolism in skeletal muscle during the recovery period was also examined. Glycogen concentration was found to decrease within 15 min and up to 2 h of recovery, while muscle glucose 6-phosphate, and the fractional activities of glycogen phosphorylase and glycogen synthase increased. From 2 to 4 h, when the glycogen synthase activity remained elevated and the phosphorylase activity declined, glycogen concentration increased, until it reached maximum values at about 24 h, after which it started to decrease, reaching control values by 72 h. At 12 and 24 h, the inverse relationship between glycogen concentration and the synthase activity ratio was lost, indicating that the reloading transiently uncoupled glycogen control of this enzyme.

Oedema and fatty degeneration of the soleus and gastrocnemius muscles on MR images in patients with Achilles tendon abnormalities.

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Hoffmann, Adrienne; Mamisch, Nadja; Buck, Florian M; Espinosa, Norman; Pfirrmann, Christian W A; Zanetti, Marco

2011-09-01

The purpose of this study was to evaluate the frequency of oedema and fatty degeneration of the soleus and gastrocnemius muscles in patients with Achilles tendon abnormalities. Forty-five consecutive patients (mean 51 years; range 14-84 years) with achillodynia were examined with magnetic resonance (MR) images of the calf. The frequency of oedema and fatty degeneration in the soleus and gastrocnemius muscles was determined in patients with normal tendons, tendinopathy and in patients with a partial tear or a complete tear of the Achilles tendon. Oedema was encountered in 35% (7/20) of the patients with tendinopathy (n = 20; range 13-81 years), and in 47% (9/19) of the patients with partial tears or complete tears (n = 19; 28-78 years). Fatty degeneration was encountered in 10% (2/20) of the patients with tendinopathy, and in 32% (6/19) of the patients with tears. The prevalence of fatty degeneration was significantly more common in patients with a partial or complete tear compared with the patients with a normal Achilles tendon (p = 0.032 and p = 0.021, respectively). Oedema and fatty degeneration of the soleus and gastrocnemius muscles are common in patients with Achilles tendon abnormalities.

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

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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

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

Differential expression of FGF receptors and of myogenic regulatory factors in primary cultures of satellite cells originating from fast (EDL) and slow (Soleus) twitch rat muscles.

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Martelly, I; Soulet, L; Bonnavaud, S; Cebrian, J; Gautron, J; Barritault, D

2000-11-01

In the rat, the fast and slow twitch muscles respectively Extensor digitorum longus (EDL) and Soleus present differential characteristics during regeneration. This suggests that their satellite cells responsible for muscle growth and repair represent distinct cellular populations. We have previously shown that satellite cells dissociated from Soleus and grown in vitro proliferate more readily than those isolated from EDL muscle. Fibroblast growth factors (FGFs) are known as regulators of myoblast proliferation and several studies have revealed a relationship between the response of myoblasts to FGF and the expression of myogenic regulatory factors (MRF) of the MyoD family by myoblasts. Therefore, we presently examined the possibility that the satellite cells isolated from EDL and Soleus muscles differ in the expression of FGF receptors (FGF-R) and of MRF expression. FGF-R1 and -R4 were strongly expressed in proliferating cultures whereas FGF-R2 and R3 were not detected in these cultures. In differentiating cultures, only -R1 was present in EDL satellite cells while FGF-R4 was also still expressed in Soleus cells. Interestingly, the unconventional receptor for FGF called cystein rich FGF receptor (CFR), of yet unknown function, was mainly detected in EDL satellite cell cultures. Soleus and EDL satellite cell cultures also differed in the expression MRFs. These results are consistent with the notion that satellite cells from fast and slow twitch muscles belong to different types of myogenic cells and suggest that satellite cells might play distinct roles in the formation and diversification of fast and slow fibres.

3D False Color Computed Tomography for Diagnosis and Follow-Up of Permanent Denervated Human Muscles Submitted to Home-Based Functional Electrical Stimulation.

Science.gov (United States)

Carraro, Ugo; Edmunds, Kyle J; Gargiulo, Paolo

2015-03-11

This report outlines the use of a customized false-color 3D computed tomography (CT) protocol for the imaging of the rectus femoris of spinal cord injury (SCI) patients suffering from complete and permanent denervation, as characterized by complete Conus and Cauda Equina syndrome. This muscle imaging method elicits the progression of the syndrome from initial atrophy to eventual degeneration, as well as the extent to which patients' quadriceps could be recovered during four years of home-based functional electrical stimulation (h-b FES). Patients were pre-selected from several European hospitals and functionally tested by, and enrolled in the EU Commission Shared Cost Project RISE (Contract n. QLG5-CT-2001-02191) at the Department of Physical Medicine, Wilhelminenspital, Vienna, Austria. Denervated muscles were electrically stimulated using a custom-designed stimulator, large surface electrodes, and customized progressive stimulation settings. Spiral CT images and specialized computational tools were used to isolate the rectus femoris muscle and produce 3D and 2D reconstructions of the denervated muscles. The cross sections of the muscles were determined by 2D Color CT, while muscle volumes were reconstructed by 3D Color CT. Shape, volume, and density changes were measured over the entirety of each rectus femoris muscle. Changes in tissue composition within the muscle were visualized by associating different colors to specified Hounsfield unit (HU) values for fat, (yellow: [-200; -10]), loose connective tissue or atrophic muscle, (cyan: [-9; 40]), and normal muscle, fascia and tendons included, (red: [41; 200]). The results from this analysis are presented as the average HU values within the rectus femoris muscle reconstruction, as well as the percentage of these tissues with respect to the total muscle volume. Results from this study demonstrate that h-b FES induces a compliance-dependent recovery of muscle volume and size of muscle fibers, as evidenced by the

Changes of contractile responses due to simulated weightlessness in rat soleus muscle

Science.gov (United States)

Elkhammari, A.; Noireaud, J.; Léoty, C.

1994-08-01

Some contractile and electrophysiological properties of muscle fibers isolated from the slow-twitch soleus (SOL) and fast-twitch extensor digitorum longus (EDL) muscles of rats were compared with those measured in SOL muscles from suspended rats. In suspendede SOL (21 days of tail-suspension) membrane potential (Em), intracellular sodium activity (aiNa) and the slope of the relationship between Em and log [K]o were typical of fast-twitch muscles. The relation between the maximal amplitude of K-contractures vs Em was steeper for control SOL than for EDL and suspended SOL muscles. After suspension, in SOL muscles the contractile threshold and the inactivation curves for K-contractures were shifted to more positive Em. Repriming of K-contractures was unaffected by suspencion. The exposure of isolated fibers to perchlorate (ClO4-)-containing (6-40 mM) solutions resulted ina similar concentration-dependent shift to more negative Em of activation curves for EDL and suspended SOL muscles. On exposure to a Na-free TEA solution, SOL from control and suspended rats, in contrast to EDL muscles, generated slow contractile responses. Suspended SOL showed a reduced sensitivity to the contracture-producing effect of caffeine compared to control muscles. These results suggested that the modification observed due to suspension could be encounted by changes in the characteristics of muscle fibers from slow to fast-twitch type.

In vivo 1D and 2D correlation MR spectroscopy of the soleus muscle at 7T

Science.gov (United States)

Ramadan, Saadallah; Ratai, Eva-Maria; Wald, Lawrence L.; Mountford, Carolyn E.

2010-05-01

AimThis study aims to (1) undertake and analyse 1D and 2D MR correlation spectroscopy from human soleus muscle in vivo at 7T, and (2) determine T1 and T2 relaxation time constants at 7T field strength due to their importance in sequence design and spectral quantitation. MethodSix healthy, male volunteers were consented and scanned on a 7T whole-body scanner (Siemens AG, Erlangen, Germany). Experiments were undertaken using a 28 cm diameter detunable birdcage coil for signal excitation and an 8.5 cm diameter surface coil for signal reception. The relaxation time constants, T1 and T2 were recorded using a STEAM sequence, using the 'progressive saturation' method for the T1 and multiple echo times for T2. The 2D L-Correlated SpectroscopY (L-COSY) method was employed with 64 increments (0.4 ms increment size) and eight averages per scan, with a total time of 17 min. ResultsT1 and T2 values for the metabolites of interest were determined. The L-COSY spectra obtained from the soleus muscle provided information on lipid content and chemical structure not available, in vivo, at lower field strengths. All molecular fragments within multiple lipid compartments were chemically shifted by 0.20-0.26 ppm at this field strength. 1D and 2D L-COSY spectra were assigned and proton connectivities were confirmed with the 2D method. ConclusionIn vivo 1D and 2D spectroscopic examination of muscle can be successfully recorded at 7T and is now available to assess lipid alterations as well as other metabolites present with disease. T1 and T2 values were also determined in soleus muscle of male healthy volunteers.

GENE RESPONSE OF THE GASTROCNEMIUS AND SOLEUS MUSCLES TO AN ACUTE AEROBIC RUN IN RATS

Directory of Open Access Journals (Sweden)

Michael J. McKenzie

2011-06-01

Full Text Available Genes can be activated or inhibited by signals within the tissues in response to an acute bout of exercise. It is unclear how a particular aerobic exercise bout may influence two muscles with similar actions to the activity. Therefore, the purposes of this investigation was to determine the gene response of selected genes involved in the "stress" response of the gastrocnemius (fast-twitch and soleus (slow-twitch muscles to a single two hour aerobic exercise bout in female Sprague-Dawley Rats at the 1 hour time point after the exercise. Exercised rats were run (n=8 for 2 hours at 20 m.min-1 and one hour after the completion of the bout had their soleus (S and gastrocnemius (G muscles removed. Age and timed matched sedentary control rats had both S and G muscles removed also. RNA was isolated from all muscles. Real-time PCR analysis was performed on the following genes: NFκB, TNFα, and Atf3. GAPDH was used as the housekeeping gene for both muscles. S muscle showed more genes altered (n = 52 vs G (n = 26. NFκB gene expression was 0.83 ± 0.14 in the exercised S but was + 1.36 ± 0.58 in the exercised G and was not significantly different between the muscles. TNFα was altered 1.30 ± 0. 34 in the exercised S and 1.36 ± 0.71 in the exercised G and was not significantly different between the muscles. The gene Atf3 was significantly altered at 4.97 ± 1.01 in the exercised S, while it was not significantly altered in the exercised G (0.70 ± 0.55. This study demonstrates that an acute bout of aerobic exercise can alter gene expression to a different extent in both the S and G muscles. It is highly likely that muscle recruitment was a factor which influenced the gene expression in theses muscles. It is interesting to note that some genes were similarly activated in these two muscles but other genes may demonstrate a varied response to the same exercise bout depending on the type of muscle

Time course of the response of carbohydrate metabolism to unloading of the soleus

Science.gov (United States)

Henriksen, Erik J.; Tischler, Marc E.

1988-01-01

The time course of the response of carbohydrate metabolism to unloading was studied in the soleus muscle of rats subjected to tail-cast suspension. In the fresh soleus, 12 hours of unloading led to higher concentrations of glycogen and lower activity ratios of both glycogen synthase and glycogen phosphorylase. These changes were still evident on day three. Thereafter, the increased glycogen concentration apparently diminished the activity ratio of glycogen synthase, leading to a subsequent fall in the total glycogen content after day one. After 24 hours of unloading, when no significant atrophy was detectable, there was no differential response to insulin for in vitro glucose metabolism. On day three, the soleus atrophied significantly and displayed a greater sensitivity to insulin for most of these parameters compared to the weight-bearing control muscle. However, insulin sensitivity for glycogen synthesis was unchanged. These results showed that the increased sensitivity to insulin of the unloaded soleus is associated with the degree of muscle atrophy, likely due to an increased insulin binding capacity relative to muscle mass. This study also showed that insulin regulation of glucose uptake and of glycogen synthesis is affected differentially in the unloaded soleus muscle.

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

The soleus syndrome. A cause of medial tibial stress (shin splints).

Science.gov (United States)

Michael, R H; Holder, L E

1985-01-01

Radionuclide bone scans have demonstrated linear uptake along the posterior medial border of the tibia in patients with shin splints. This area was investigated by anatomical dissection (14 human cadavers), electromyographic (EMG) and muscle stimulation studies (10 patients), and open biopsy (1 patient). Histologically, the increased metabolic activity manifested on the radionuclide scan is due to a periostitis with new bone formation. The soleus muscle and its investing fascia are anatomically and biomechanically implicated in the production of these stress changes, particularly when the heel is in the pronated position. The soleus muscle and fascia form a tough "soleus bridge" over the deep compartment which is thought to be important in patients requiring surgical decompression.

3D false color computed tomography for diagnosis and follow-up of permanent denervated human muscles submitted to home-based Functional Electrical Stimulation

Directory of Open Access Journals (Sweden)

Ugo Carraro

2015-03-01

Full Text Available This report outlines the use of a customized false-color 3D computed tomography (CT protocol for the imaging of the rectus femoris of spinal cord injury (SCI patients suffering from complete and permanent denervation, as characterized by complete Conus and Cauda Equina syndrome. This muscle imaging method elicits the progression of the syndrome from initial atrophy to eventual degeneration, as well as the extent to which patients' quadriceps could be recovered during four years of home-based functional electrical stimulation (h-b FES. Patients were pre-selected from several European hospitals and functionally tested by, and enrolled in the EU Commission Shared Cost Project RISE (Contract n. QLG5-CT-2001-02191 at the Department of Physical Medicine, Wilhelminenspital, Vienna, Austria. Denervated muscles were electrically stimulated using a custom-designed stimulator, large surface electrodes, and customized progressive stimulation settings. Spiral CT images and specialized computational tools were used to isolate the rectus femoris muscle and produce 3D and 2D reconstructions of the denervated muscles. The cross sections of the muscles were determined by 2D Color CT, while muscle volumes were reconstructed by 3D Color CT. Shape, volume, and density changes were measured over the entirety of each rectus femoris muscle. Changes in tissue composition within the muscle were visualized by associating different colors to specified Hounsfield unit (HU values for fat, (yellow: [-200; -10], loose connective tissue or atrophic muscle, (cyan: [-9; 40], and normal muscle, fascia and tendons included, (red: [41; 200]. The results from this analysis are presented as the average HU values within the rectus femoris muscle reconstruction, as well as the percentage of these tissues with respect to the total muscle volume. Results from this study demonstrate that h-b FES induces a compliance-dependent recovery of muscle volume and size of muscle fibers, as

Soleus and lateral gastrocnemius H-reflexes during standing with unstable footwear.

Science.gov (United States)

Friesenbichler, Bernd; Lepers, Romuald; Maffiuletti, Nicola A

2015-05-01

Unstable footwear has been shown to increase lower extremity muscle activity, but the reflex response to perturbations induced by this intervention is unknown. Twenty healthy subjects stood in stable and unstable footwear conditions (presented randomly) while H-reflex amplitude and background muscle activity were measured in the soleus and lateral gastrocnemius (LG) muscles. Wearing unstable footwear resulted in larger H-reflexes (normalized to the maximal M-wave) for the LG (+12%; P = 0.025), but not for the soleus (+4%; P > 0.05). Background activity of both muscles was significantly higher in the unstable condition. The H-reflex facilitation observed with unstable footwear was unexpected, as challenging postural conditions usually result in reflex depression. Increased muscle activity, decreased presynaptic inhibition, and/or more forward postural position may have (over-)compensated the expected reflex depression. Differences between LG and soleus H-reflex modulation may be due to diverging motor unit recruitment thresholds. © 2015 Wiley Periodicals, Inc.

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

Science.gov (United States)

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

2013-09-01

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

The role of subscapularis muscle denervation in the pathogenesis of shoulder internal rotation contracture after neonatal brachial plexus palsy: a study in a rat model.

Science.gov (United States)

Mascarenhas, Vasco V; Casaccia, Marcelo; Fernandez-Martin, Alejandra; Marotta, Mario; Fontecha, Cesar G; Haddad, Sleiman; Knörr, Jorge; Soldado, Francisco

2014-12-01

We assessed the role of subscapularis muscle denervation in the development of shoulder internal rotation contracture in neonatal brachial plexus injury. Seventeen newborn rats underwent selective denervation of the subscapular muscle. The rats were evaluated at weekly intervals to measure passive shoulder external rotation. After 4 weeks, the animals were euthanized. The subscapularis thickness was measured using 7.2T MRI axial images. The subscapularis muscle was then studied grossly, and its mass was registered. The fiber area and the area of fibrosis were measured using collagen-I inmunostained muscle sections. Significant progressive decrease in passive shoulder external rotation was noted with a mean loss of 58° at four weeks. A significant decrease in thickness and mass of the subscapularis muscles in the involved shoulders was also found with a mean loss of 69%. Subscapularis muscle fiber size decreased significantly, while the area of fibrosis remained unchanged. Our study shows that subscapularis denervation, per se, could explain shoulder contracture after neonatal brachial plexus injury, though its relevance compared to other pathogenic factors needs further investigation. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Effects of hypothyroidism on the sensitivity of glycolysis and glycogen synthesis to insulin in the soleus muscle of the rat.

Science.gov (United States)

Dimitriadis, G D; Leighton, B; Parry-Billings, M; West, D; Newsholme, E A

1989-01-01

1. The effects of hypothyroidism on the sensitivity of glycolysis and glycogen synthesis to insulin were investigated in the isolated, incubated soleus muscle of the rat. 2. Hypothyroidism, which was induced by administration of propylthiouracil to the rats, decreased fasting plasma levels of free fatty acids and increased plasma levels of glucose but did not significantly change plasma levels of insulin. 3. The sensitivity of the rates of glycogen synthesis to insulin was increased at physiological, but decreased at supraphysiological, concentrations of insulin. 4. The rates of glycolysis in the hypothyroid muscles were decreased at all insulin concentrations studied and the EC50 for insulin was increased more than 8-fold; the latter indicates decreased sensitivity of this process to insulin. However, at physiological concentrations of insulin, the rates of glucose phosphorylation in the soleus muscles of hypothyroid rats were not different from controls. This suggests that hypothyroidism affects glucose metabolism in muscle not by affecting glucose transport but by decreasing the rate of glucose 6-phosphate conversion to lactate and increasing the rate of conversion of glucose 6-phosphate to glycogen. 5. The rates of glucose oxidation were decreased in the hypothyroid muscles at all insulin concentrations. PMID:2649073

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.

Lack of on-going adaptations in the soleus muscle activity during walking in patients affected by large-fiber neuropathy

DEFF Research Database (Denmark)

Nazarena, Mazzaro; Grey, Michael James; Sinkjær, Thomas

2005-01-01

The aim of this study was to investigate the contribution of feedback from large-diameter sensory fibers to the adaptation of soleus muscle activity after small ankle trajectory modifications during human walking. Small-amplitude and slow-velocity ankle dorsiflexion enhancements and reductions were...... applied during the stance phase of the gait cycle to mimic the normal variability of the ankle trajectory during walking. Patients with demyelination of large sensory fibers (Charcot-Marie-Tooth type 1A and antibodies to myelin-associated glycoprotein neuropathy) and age-matched controls participated...... duration (P ankle dorsiflexion was, respectively, enhanced or reduced. In the patients, the soleus EMG increased during the dorsiflexion...

Decreased rate of protein synthesis, caspase-3 activity, and ubiquitin-proteasome proteolysis in soleus muscles from growing rats fed a low-protein, high-carbohydrate diet.

Science.gov (United States)

Batistela, Emanuele; Pereira, Mayara Peron; Siqueira, Juliany Torres; Paula-Gomes, Silvia; Zanon, Neusa Maria; Oliveira, Eduardo Brandt; Navegantes, Luiz Carlos Carvalho; Kettelhut, Isis C; Andrade, Claudia Marlise Balbinotti; Kawashita, Nair Honda; Baviera, Amanda Martins

2014-06-01

The aim of this study was to investigate the changes in the rates of both protein synthesis and breakdown, and the activation of intracellular effectors that control these processes in soleus muscles from growing rats fed a low-protein, high-carbohydrate (LPHC) diet for 15 days. The mass and the protein content, as well as the rate of protein synthesis, were decreased in the soleus from LPHC-fed rats. The availability of amino acids was diminished, since the levels of various essential amino acids were decreased in the plasma of LPHC-fed rats. Overall rate of proteolysis was also decreased, explained by reductions in the mRNA levels of atrogin-1 and MuRF-1, ubiquitin conjugates, proteasome activity, and in the activity of caspase-3. Soleus muscles from LPHC-fed rats showed increased insulin sensitivity, with increased levels of insulin receptor and phosphorylation levels of AKT, which probably explains the inhibition of both the caspase-3 activity and the ubiquitin-proteasome system. The fall of muscle proteolysis seems to represent an adaptive response that contributes to spare proteins in a condition of diminished availability of dietary amino acids. Furthermore, the decreased rate of protein synthesis may be the driving factor to the lower muscle mass gain in growing rats fed the LPHC diet.

Imaging of denervation in the head and neck

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Borges, Alexandra [Radiology Department, Instituto Portugues de Oncologia Francisco Gentil, Centro de Lisboa, Rua Prof. Lima Basto, 1093 Lisboa (Portugal)], E-mail: borgalexandra@gmail.com

2010-05-15

Denervation changes maybe the first sign of a cranial nerve injury. Recognition of denervation patterns can be used to determine the site and extent of a lesion and to tailor imaging studies according to the most likely location of an insult along the course of the affected cranial nerve(s). In addition, the extent of denervation can be used to predict functional recovery after treatment. On imaging, signs of denervation can be misleading as they often mimic recurrent neoplasm or inflammatory conditions. Imaging can both depict denervation related changes and establish its cause. This article briefly reviews the anatomy of the extracranial course of motor cranial nerves with particular emphasis on the muscles supplied by each nerve, the imaging features of the various stages of denervation, the different patterns of denervation that maybe helpful in the topographic diagnosis of nerve lesions and the most common causes of cranial nerve injuries leading to denervation.

Imaging of denervation in the head and neck.

Science.gov (United States)

Borges, Alexandra

2010-05-01

Denervation changes maybe the first sign of a cranial nerve injury. Recognition of denervation patterns can be used to determine the site and extent of a lesion and to tailor imaging studies according to the most likely location of an insult along the course of the affected cranial nerve(s). In addition, the extent of denervation can be used to predict functional recovery after treatment. On imaging, signs of denervation can be misleading as they often mimic recurrent neoplasm or inflammatory conditions. Imaging can both depict denervation related changes and establish its cause. This article briefly reviews the anatomy of the extracranial course of motor cranial nerves with particular emphasis on the muscles supplied by each nerve, the imaging features of the various stages of denervation, the different patterns of denervation that maybe helpful in the topographic diagnosis of nerve lesions and the most common causes of cranial nerve injuries leading to denervation. Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.

Imaging of denervation in the head and neck

International Nuclear Information System (INIS)

Borges, Alexandra

2010-01-01

Denervation changes maybe the first sign of a cranial nerve injury. Recognition of denervation patterns can be used to determine the site and extent of a lesion and to tailor imaging studies according to the most likely location of an insult along the course of the affected cranial nerve(s). In addition, the extent of denervation can be used to predict functional recovery after treatment. On imaging, signs of denervation can be misleading as they often mimic recurrent neoplasm or inflammatory conditions. Imaging can both depict denervation related changes and establish its cause. This article briefly reviews the anatomy of the extracranial course of motor cranial nerves with particular emphasis on the muscles supplied by each nerve, the imaging features of the various stages of denervation, the different patterns of denervation that maybe helpful in the topographic diagnosis of nerve lesions and the most common causes of cranial nerve injuries leading to denervation.

Reduced sarcoplasmic reticulum content of releasable Ca2+ in rat soleus muscle fibres after eccentric contractions

DEFF Research Database (Denmark)

Nielsen, J S; Sahlin, K; Ørtenblad, N

2007-01-01

AIM: The purpose was to evaluate the effects of fatiguing eccentric contractions (EC) on calcium (Ca2+) handling properties in mammalian type I muscles. We hypothesized that EC reduces both endogenous sarcoplasmic reticulum (SR) content of releasable Ca2+ (eSRCa2+) and myofibrillar Ca2+ sensitivity....... METHODS: Isolated rat soleus muscles performed 30 EC bouts. Single fibres were isolated from the muscle and after mechanical removal of sarcolemma used to measure eSRCa2+, rate of SR Ca2+ loading and myofibrillar Ca2+ sensitivity. RESULTS: Following EC maximal force in whole muscle was reduced by 30......% and 16/100 Hz force ratio by 33%. The eSRCa2+ in fibres from non-stimulated muscles was 45 +/- 5% of the maximal loading capacity. After EC, eSRCa2+ per fibre CSA decreased by 38% (P = 0.05), and the maximal capacity of SR Ca2+ loading was depressed by 32%. There were no effects of EC on either...

Denervation syndromes of the shoulder girdle: MR imaging with electrophysiologic correlation

International Nuclear Information System (INIS)

Bredella, M.A.; Wischer, T.K.; Stork, A.; Genant, H.K.; Tirman, P.F.J.; Fritz, R.C.

1999-01-01

Objective. To investigate the use of MR imaging in the characterization of denervated muscle of the shoulder correlated with electrophysiologic studies.Design and patients. We studied with MR imaging five patients who presented with shoulder weakness and pain and who underwent electrophysiologic studies. On MR imaging the distribution of muscle edema and fatty infiltration was recorded, as was the presence of masses impinging on a regional nerve.Results. Acute/subacute denervation was best seen on T2-weighted fast spin-echo images with fat saturation, showing increased SI related to neurogenic edema. Chronic denervation was best seen on T1-weighted spin-echo images, demonstrating loss of muscle bulk and diffuse areas of increased signal intensity within the muscle. Three patients showed MR imaging and electrophysiologic findings of Parsonage Turner syndrome. One patient demonstrated an arteriovenous malformation within the spinoglenoid notch, impinging on the suprascapular nerve with associated atrophy of the infraspinatus muscle. The fifth patient demonstrated fatty atrophy of the teres minor muscle caused by compression by a cyst of the axillary nerve and electrophysiologic findings of an incomplete axillary nerve block.Conclusion. MR imaging is useful in detecting and characterizing denervation atrophy and neurogenic edema in shoulder muscles. MR imaging can provide additional information to electrophysiologic studies by estimating the age (acute/chronic) and identifying morphologic causes for shoulder pain and atrophy. (orig.)

Effect of triiodothyronine (T3) excess on fatty acid metabolism in the soleus muscle from endurance-trained rats.

Science.gov (United States)

Górecka, M; Synak, M; Brzezińska, Z; Dąbrowski, J; Żernicka, E

2016-04-01

We studied whether short-term administration of triiodothyronine (T3) for the last 3 days of endurance training would influence the rate of uptake of palmitic acid (PA) as well as metabolism in rat soleus muscle, in vitro. Training per se did not affect the rate of PA uptake by the soleus; however, an excess of T3 increased the rate of this process at 1.5 mmol/L PA, as well as the rate that at which PA was incorporated into intramuscular triacylglycerols (TG). The rate of TG synthesis in trained euthyroid rats was reduced after exercise (1.5 mmol/L PA). The rate of PA oxidation in all of the trained rats immediately after exercise was enhanced by comparison with the sedentary values. Hyperthyroidism additionally increased the rate of this process at 1.5 mmol/L PA. After a recovery period, the rate of PA oxidation returned to the control values in both the euthyroid and the hyperthyroid groups. Examination of the high-energy phosphate levels indicated that elevated PA oxidation after exercise-training in euthyroid rats was associated with stable ATP levels and increased ADP and AMP levels, thus reducing energy cellular potential (ECP). In the hyperthyroid rats, levels of ADP and AMP were increased in the sedentary as well as the exercise-trained rats. ECP levels were high as a result of high levels of ATP and decreased levels of ADP and AMP in hyperthyroid rats after the recovery period. In conclusion, short-term hyperthyroidism accelerates PA utilization in well-trained soleus muscle.

Decreased contribution from afferent feedback to the soleus muscle during walking in patients with spastic stroke

DEFF Research Database (Denmark)

Mazzaro, Nazarena; Nielsen, Jørgen Feldbæk; Grey, Michael James

2007-01-01

We investigated the contribution of afferent feedback to the soleus (SOL) muscle activity during the stance phase of walking in patients with spastic stroke. A total of 24 patients with hemiparetic spastic stroke and age-matched healthy volunteers participated in the study. A robotic actuator...... by the Ashworth score. These results indicate that although the stretch reflex response is facilitated during spastic gait, the contribution of afferent feedback to the ongoing locomotor SOL activity is depressed in patients with spastic stroke....

Exercise training in Tgαq*44 mice during the progression of chronic heart failure: cardiac vs. peripheral (soleus muscle) impairments to oxidative metabolism.

Science.gov (United States)

Grassi, Bruno; Majerczak, Joanna; Bardi, Eleonora; Buso, Alessia; Comelli, Marina; Chlopicki, Stefan; Guzik, Magdalena; Mavelli, Irene; Nieckarz, Zenon; Salvadego, Desy; Tyrankiewicz, Urszula; Skórka, Tomasz; Bottinelli, Roberto; Zoladz, Jerzy A; Pellegrino, Maria Antonietta

2017-08-01

Cardiac function, skeletal (soleus) muscle oxidative metabolism, and the effects of exercise training were evaluated in a transgenic murine model (Tgα q *44) of chronic heart failure during the critical period between the occurrence of an impairment of cardiac function and the stage at which overt cardiac failure ensues (i.e., from 10 to 12 mo of age). Forty-eight Tgα q *44 mice and 43 wild-type FVB controls were randomly assigned to control groups and to groups undergoing 2 mo of intense exercise training (spontaneous running on an instrumented wheel). In mice evaluated at the beginning and at the end of training we determined: exercise performance (mean distance covered daily on the wheel); cardiac function in vivo (by magnetic resonance imaging); soleus mitochondrial respiration ex vivo (by high-resolution respirometry); muscle phenotype [myosin heavy chain (MHC) isoform content; citrate synthase (CS) activity]; and variables related to the energy status of muscle fibers [ratio of phosphorylated 5'-AMP-activated protein kinase (AMPK) to unphosphorylated AMPK] and mitochondrial biogenesis and function [peroxisome proliferative-activated receptor-γ coactivator-α (PGC-1α)]. In the untrained Tgα q *44 mice functional impairments of exercise performance, cardiac function, and soleus muscle mitochondrial respiration were observed. The impairment of mitochondrial respiration was related to the function of complex I of the respiratory chain, and it was not associated with differences in CS activity, MHC isoforms, p-AMPK/AMPK, and PGC-1α levels. Exercise training improved exercise performance and cardiac function, but it did not affect mitochondrial respiration, even in the presence of an increased percentage of type 1 MHC isoforms. Factors "upstream" of mitochondria were likely mainly responsible for the improved exercise performance. NEW & NOTEWORTHY Functional impairments in exercise performance, cardiac function, and soleus muscle mitochondrial respiration

Cytoskeleton, L-type Ca2+ and stretch activated channels in injured skeletal muscle

Directory of Open Access Journals (Sweden)

Fabio Francini

2013-07-01

Full Text Available The extra-sarcomeric cytoskeleton (actin microfilaments and anchoring proteins is involved in maintaining the sarco-membrane stiffness and integrity and in turn the mechanical stability and function of the intra- and sub-sarcoplasmic proteins. Accordingly, it regulates Ca2+ entry through the L-type Ca2+ channels and the mechano-sensitivity of the stretch activated channels (SACs. Moreover, being intra-sarcomeric cytoskeleton bound to costameric proteins and other proteins of the sarcoplasma by intermediate filaments, as desmin, it integrates the properties of the sarcolemma with the skeletal muscle fibres contraction. The aim of this research was to compare the cytoskeleton, SACs and the ECC alterations in two different types of injured skeletal muscle fibres: by muscle denervation and mechanical overload (eccentric contraction. Experiments on denervation were made in isolated Soleus muscle of male Wistar rats; forced eccentric-contraction (EC injury was achieved in Extensor Digitorum Longus muscles of Swiss mice. The method employed conventional intracellular recording with microelectrodes inserted in a single fibre of an isolated skeletal muscle bundle. The state of cytoskeleton was evaluated by recording SAC currents and by evaluating the resting membrane potential (RMP value determined in current-clamp mode. The results demonstrated that in both injured skeletal muscle conditions the functionality of L-type Ca2+ current, ICa, was affected. In parallel, muscle fibres showed an increase of the resting membrane permeability and of the SAC current. These issues, together with a more depolarized RMP are an index of altered cytoskeleton. In conclusion, we found a symilar alteration of ICa, SAC and cytoskeleton in both injured skeletal muscle conditions.

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

Science.gov (United States)

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.

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.

Loss of cIAP1 attenuates soleus muscle pathology and improves diaphragm function in mdx mice

Science.gov (United States)

Enwere, Emeka K.; Boudreault, Louise; Holbrook, Janelle; Timusk, Kristen; Earl, Nathalie; LaCasse, Eric; Renaud, Jean-Marc; Korneluk, Robert G.

2013-01-01

The cellular inhibitor of apoptosis 1 (cIAP1) protein is an essential regulator of canonical and noncanonical nuclear factor κB (NF-κB) signaling pathways. NF-κB signaling is known to play important roles in myogenesis and degenerative muscle disorders such as Duchenne muscular dystrophy (DMD), but the involvement of cIAP1 in muscle disease has not been studied directly. Here, we asked whether the loss of cIAP1 would influence the pathology of skeletal muscle in the mdx mouse model of DMD. Double-mutant cIAP1−/−;mdx mice exhibited reduced muscle damage and decreased fiber centronucleation in the soleus, compared with single-mutant cIAP1+/+;mdx mice. This improvement in pathology was associated with a reduction in muscle infiltration by macrophages and diminished expression of inflammatory cytokines such as IL-6 and tumor necrosis factor-α. Furthermore, the cIAP1−/−;mdx mice exhibited reduced serum creatine kinase, and improved exercise endurance associated with improved exercise resilience by the diaphragm. Mechanistically, the loss of cIAP1 was sufficient to drive constitutive activation of the noncanonical NF-κB pathway, which led to increased myoblast fusion in vitro and in vivo. Collectively, these results show that the loss of cIAP1 protects skeletal muscle from the degenerative pathology resulting from systemic loss of dystrophin. PMID:23184147

Musculoskeletal growth in the upper arm in infants after obstetric brachial plexus lesions partial denervation and its relation with residual muscle function

NARCIS (Netherlands)

Ruoff, J.M.; van der Sluijs, J.A.; van Ouwerkerk, W.J.R.; Jaspers, R.T.

2012-01-01

Aim Denervation after obstetric brachial plexus lesion (OBPL) is associated with reduced musculoskeletal growth in the upper arm. The aim of this study was to investigate whether reduced growth of upper arm flexor and extensor muscles is related to active elbow function and humeral length. Method In

CT-guided injection of botulinic toxin for percutaneous therapy of piriformis muscle syndrome with preliminary MRI results about denervative process

Energy Technology Data Exchange (ETDEWEB)

Fanucci, E.; Masala, S.; Sodani, G.; Varrucciu, V.; Romagnoli, A.; Squillaci, E.; Simonetti, G. [Dept. of Radiology, Univ. of Rome (Italy)

2001-12-01

Piriformis muscle syndrome (PMS) is a cause of sciatica, leg or buttock pain and disability. The pain is usually increased by muscular contraction, palpation or prolonged sitting. The aim of our paper was to evaluate the feasibility of CT-guided percutaneous botulinic toxin (BTX) injection for the purpose of PMS treatment. Thirty patients suffering from PMS, suspected with clinical and electrophysiological criteria, after imaging examinations excluding other causes of sciatic pain, resulted positive at the lidocaine test and were treated by intramuscular injection of BTX type A under CT guidance. The follow-up (12 months) was performed with clinical examination in all cases and with MR 3 months after the procedure in 9 patients to evaluate the denervative process entity of the treated muscle. In 26 cases relief of symptoms was obtained after 5-7 days. In 4 patients an insufficient relief of pain justified a second percutaneous treatment which was clinically successful. No complications or side effects were recorded after BTX injection. The MR examination showed a signal intensity change of the treated muscle in 7 patients due to the denervative process of PM, whereas in the remaining 2 cases only an atrophy of the treated muscle was detected. Larger series are necessary to confirm these MRI preliminary results. The CT-guided BTX injection in the PMS is an emergent and feasible technique that obtains an excellent local therapeutic effect without risk of imprecise inoculation. (orig.)

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

Science.gov (United States)

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

2016-05-01

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

Medial gastrocnemius and soleus muscle-tendon unit, fascicle, and tendon interaction during walking in children with cerebral palsy.

Science.gov (United States)

Barber, Lee; Carty, Chris; Modenese, Luca; Walsh, John; Boyd, Roslyn; Lichtwark, Glen

2017-08-01

This study investigates the in vivo function of the medial gastrocnemius and soleus muscle-tendon units (MTU), fascicles, and tendons during walking in children with cerebral palsy (CP) and an equinus gait pattern. Fourteen children with CP (9 males, 5 females; mean age 10y 6mo, standard deviation [SD] 2y 11mo; GMFCS level I=8, II=6), and 10 typically developing (6 males, 4 females; mean age 10y, SD 2y 1mo) undertook full body 3D gait analysis and simultaneous B-mode ultrasound images of the medial gastrocnemius and soleus fascicles during level walking. Fascicle lengths were analysed using a semi-automated tracking algorithm and MTUs using OpenSim. Statistical parametric mapping (two-sample t-test) was used to compare differences between groups (ppower during push-off (p=0.015) and positive work (ppower and positive work in the children with CP may be attributed to reduced active medial gastrocnemius fascicle shortening. These findings suggest a reliance on passive force generation for forward propulsion during equinus gait. © 2017 Mac Keith Press.

The effects of running exercise on oxidative capacity and PGC-1α mRNA levels in the soleus muscle of rats with metabolic syndrome.

Science.gov (United States)

Nagatomo, Fumiko; Fujino, Hidemi; Kondo, Hiroyo; Kouzaki, Motoki; Gu, Ning; Takeda, Isao; Tsuda, Kinsuke; Ishihara, Akihiko

2012-03-01

Skeletal muscles in animals with metabolic syndrome exhibit reduced oxidative capacity. We investigated the effects of running exercise on fiber characteristics, oxidative capacity, and mRNA levels in the soleus muscles of rats with metabolic syndrome [SHR/NDmcr-cp (cp/cp); CP]. We divided 5-week-old CP rats into non-exercise (CP) and exercise (CP-Ex) groups. Wistar-Kyoto rats (WKY) were used as the control group. CP-Ex rats were permitted voluntary exercise on running wheels for 10 weeks. Triglyceride levels were higher and adiponectin levels lower in the CP and CP-Ex groups than in the WKY group. However, triglyceride levels were lower and adiponectin levels higher in the CP-Ex group than in the CP group. The soleus muscles in CP-Ex rats contained only high-oxidative type I fibers, whereas those in WKY and CP rats contained type I, IIA, and IIC fibers. Muscle succinate dehydrogenase (SDH) activity was higher in the CP-Ex group than in the CP group; there was no difference in SDH activity between the WKY and CP-Ex groups. Muscle proliferator-activated receptor γ coactivator-1α (PGC-1α) mRNA levels were higher in the CP-Ex group than in the CP group; there was no difference in PGC-1α mRNA levels between the WKY and CP-Ex groups. In CP-Ex rats, longer running distance was associated with increased muscle SDH activity and PGC-1α mRNA levels. We concluded that running exercise restored decreased muscle oxidative capacity and PGC-1α mRNA levels and improved hypertriglyceridemia in rats with metabolic syndrome.

Facilitation of soleus but not tibialis anterior motor evoked potentials before onset of antagonist contraction

DEFF Research Database (Denmark)

Geertsen, Svend Sparre; Zuur, Abraham Theodore; Nielsen, Jens Bo

2008-01-01

Objective: It is well documented that corticospinal projections to motoneurons of one muscle inhibit antagonist motoneurons through collaterals to reciprocally organized spinal inhibitory interneurons. During and just prior to dorsiflexion of the ankle, soleus motoneurons are thus inhibited...... the MEP is evoked. Methods: Seated subjects (n=11) were instructed to react to an auditory cue by contracting either the tibialis anterior (TA) or soleus muscle of the left ankle to 30% of their maximal dorsiflexion voluntary contraction (MVC) or plantar flexion MVC, respectively. Focal TMS at 1.2 x motor...

MRI detection of soleus muscle injuries in professional football players

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Pezzotta, G.; Querques, G.; Pecorelli, A.; Nani, R.; Sironi, S. [Papa Giovanni XXIII Hospital, University Milano-Bicocca, Department of Radiology, Bergamo (Italy)

2017-11-15

To describe magnetic resonance imaging (MRI) characteristics of soleus muscle injuries in symptomatic professional football players stratified according to both the Munich consensus statement and the British Athletics Muscle Injury Classification (BAMIC), and to investigate the association between specific MRI features and the ''return to play'' (RTP). Professional football players with an episode of acute posterior calf pain and impaired function, subsequent to sports activity, underwent ultrasound followed by MRI examination reviewed by two different radiologists with more than 10 years of experience in the musculoskeletal system. MRI features and RTP outcome were evaluated for all types of injuries. During a 36-month period, a total of 20 professional football players were evaluated. According to the Munich consensus, 11 were type 3A, 8 were type 3B, and 1 was type 4, whereas according to the BAMIC, 11 lesions were considered grade 1, 4 grade 2, 4 grade 3, and 1 grade 4. RTP data were available for all patients (mean 3.3 ± 1.6 weeks). Both the Munich consensus and the BAMIC correlated with RTP (Spearman correlation = 0.982 and p < 0.0001 and 0.886 and p < 0.0001 respectively). Extension of edema was an independent prognostic factor for RTP in two different models of multivariate regression analysis (p = 0.044 model A; p = 0.031 model B). The Munich consensus and BAMIC grading systems are useful tools for defining the patient's prognosis and proper rehabilitation time after injury. The MRI feature that we should carefully look for is the extension of edema, as it seems to significantly affect the RTP. (orig.)

MRI detection of soleus muscle injuries in professional football players

International Nuclear Information System (INIS)

Pezzotta, G.; Querques, G.; Pecorelli, A.; Nani, R.; Sironi, S.

2017-01-01

To describe magnetic resonance imaging (MRI) characteristics of soleus muscle injuries in symptomatic professional football players stratified according to both the Munich consensus statement and the British Athletics Muscle Injury Classification (BAMIC), and to investigate the association between specific MRI features and the ''return to play'' (RTP). Professional football players with an episode of acute posterior calf pain and impaired function, subsequent to sports activity, underwent ultrasound followed by MRI examination reviewed by two different radiologists with more than 10 years of experience in the musculoskeletal system. MRI features and RTP outcome were evaluated for all types of injuries. During a 36-month period, a total of 20 professional football players were evaluated. According to the Munich consensus, 11 were type 3A, 8 were type 3B, and 1 was type 4, whereas according to the BAMIC, 11 lesions were considered grade 1, 4 grade 2, 4 grade 3, and 1 grade 4. RTP data were available for all patients (mean 3.3 ± 1.6 weeks). Both the Munich consensus and the BAMIC correlated with RTP (Spearman correlation = 0.982 and p < 0.0001 and 0.886 and p < 0.0001 respectively). Extension of edema was an independent prognostic factor for RTP in two different models of multivariate regression analysis (p = 0.044 model A; p = 0.031 model B). The Munich consensus and BAMIC grading systems are useful tools for defining the patient's prognosis and proper rehabilitation time after injury. The MRI feature that we should carefully look for is the extension of edema, as it seems to significantly affect the RTP. (orig.)

MRI detection of soleus muscle injuries in professional football players.

Science.gov (United States)

Pezzotta, G; Querques, G; Pecorelli, A; Nani, R; Sironi, S

2017-11-01

To describe magnetic resonance imaging (MRI) characteristics of soleus muscle injuries in symptomatic professional football players stratified according to both the Munich consensus statement and the British Athletics Muscle Injury Classification (BAMIC), and to investigate the association between specific MRI features and the "return to play" (RTP). Professional football players with an episode of acute posterior calf pain and impaired function, subsequent to sports activity, underwent ultrasound followed by MRI examination reviewed by two different radiologists with more than 10 years of experience in the musculoskeletal system. MRI features and RTP outcome were evaluated for all types of injuries. During a 36-month period, a total of 20 professional football players were evaluated. According to the Munich consensus, 11 were type 3A, 8 were type 3B, and 1 was type 4, whereas according to the BAMIC, 11 lesions were considered grade 1, 4 grade 2, 4 grade 3, and 1 grade 4. RTP data were available for all patients (mean 3.3 ± 1.6 weeks). Both the Munich consensus and the BAMIC correlated with RTP (Spearman correlation = 0.982 and p < 0.0001 and 0.886 and p < 0.0001 respectively). Extension of edema was an independent prognostic factor for RTP in two different models of multivariate regression analysis (p = 0.044 model A; p = 0.031 model B). The Munich consensus and BAMIC grading systems are useful tools for defining the patient's prognosis and proper rehabilitation time after injury. The MRI feature that we should carefully look for is the extension of edema, as it seems to significantly affect the RTP.

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

Collagen content in the vastus lateralis and the soleus muscle following a 90-day bed rest period with or without resistance exercises

DEFF Research Database (Denmark)

Nielsen, Rasmus Oestergaard; Schjerling, Peter; Tesch, Per

2015-01-01

training serves as a proxy for the conditions in space. Therefore, ground-based studies may improve the understanding of the consequences of long-term inactivity. PURPOSE: the purpose is to compare the change in collagen protein in the vastus lateralis (VL) and the soleus (SOL) muscle amongst persons......INTRODUCTION: spaceflight seems associated with deterioration of the function of the skeletal muscles. Since muscle collagen is critical for muscle function, an improved understanding of the content of the muscle collagen during long-term inactivity seems important. Bed-rest with in-bed resistance...... collagen/mg protein [95% CI: -25.6; 12.6], p=0.50). There was no difference in the effect of BR versus BRE over time (mean difference -2.78 μg collagen/mg protein [95% CI: -29.7; 24.1], p=0.82). CONCLUSION: muscle collagen content in the VL or SOL muscle does not seem to differ after a 90-day bed rest...

Effect of altered thyroid state on the in situ mechanical properties of adult cat soleus

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Roy, R. R.; Zhong, H.; Hodgson, J. A.; Grossman, E. J.; Edgerton, V. R.

2003-01-01

To determine the responsiveness of cat hindlimb muscles to thyroid manipulation, adult female cats were made hypothyroid (thyroidectomy plus tapazole treatment), hyperthyroid (synthroid pellets), or maintained euthyroid. After 4 months, the hypothyroid soleus had slower time-to-peak (TPT, 80%) and half-relaxation (HRT) times, whereas the hyperthyroid soleus had faster TPT (20%) and HRT than euthyroid cats. The tension at low stimulation frequencies (5-15 Hz) was higher in hypothyroid and lower in hyperthyroid cats compared to euthyroid cats. Muscle weight, maximum twitch and tetanic (Po) tensions, and maximum rates of shortening (Vmax) were similar across groups. The soleus of hypothyroid cats was more fatigable than normal. The myosin heavy chain (MHC) composition, based on gel electrophoresis, was unaffected by thyroid hormone manipulation. Based on the reaction of monoclonal antibodies for specific MHCs, some fast fibers in the hypothyroid cats coexpressed developmental MHC. These data indicate that 4 months of an altered thyroid state result in changes in the isometric twitch speed properties of the cat soleus, but not the tension-related or isotonic properties. Further, a chronic decrease in thyroid hormone had a greater impact than a chronic increase in thyroid hormone on the mechanical properties of the adult cat soleus. Copyright 2003 S. Karger AG, Basel.

Effects of insulin and epinephrine on Na+-K+ and glucose transport in soleus muscle

International Nuclear Information System (INIS)

Clausen, T.; Flatman, J.A.

1987-01-01

To identify possible cause-effect relationships between changes in active Na + -K + transport, resting membrane potential, and glucose transport, the effects of insulin and epinephrine were compared in rat soleus muscle. Epinephrine, which produced twice as large a hyperpolarization as insulin, induced only a modest increase in 14 C-labeled sugar transport. Ouabain, at a concentration (10 -3 M) sufficient to block active Na + -K + transport and the hyperpolarization induced by the two hormones, did not interfere with sugar transport stimulation. After Na + loading in K + -free buffer, the return to K + -containing standard buffer caused marked stimulation of active 22 Na + - 42 K + transport, twice the hyperpolarization produced by insulin but no change in sugar transport. The insulin-induced activation of the 22 Na + - 42 K + pump leads to decreased intracellular 22 Na + concentration and hyperpolarization, but none of these events can account for the concomitant activation of the glucose transport system. The stimulating effect of insulin on active Na + -K + transport was not suppressed by amiloride, indicating that in intact skeletal muscle it is not elicited by a primary increase in Na + influx via the Na + /H + -exchange system

Overexpression of IGF-1 attenuates skeletal muscle damage and accelerates muscle regeneration and functional recovery after disuse

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Ye, Fan; Mathur, Sunita; Liu, Min; Borst, Stephen E.; Walter, Glenn A.; Sweeney, H. Lee; Vandenborne, Krista

2014-01-01

Skeletal muscle is a highly dynamic tissue that responds to endogenous and external stimuli, including alterations in mechanical loading and growth factors. In particular, the antigravity soleus muscle experiences significant muscle atrophy during disuse and extensive muscle damage upon reloading. Since insulin-like growth factor-1 (IGF-1) has been implicated as a central regulator of muscle repair and modulation of muscle size, we examined the effect of viral mediated overexpression of IGF-1 on the soleus muscle following hindlimb cast immobilization and upon reloading. Recombinant IGF-1 cDNA virus was injected into one of the posterior hindlimbs of the mice, while the contralateral limb was injected with saline (control). At 20 weeks of age, both hindlimbs were immobilized for two weeks to induce muscle atrophy in the soleus and ankle plantar flexor muscle group. Subsequently, the mice were allowed to reambulate and muscle damage and recovery was monitored over a period of 2 to 21 days. The primary finding of this study was that IGF-1 overexpression attenuated reloading-induced muscle damage in the soleus muscle, and accelerated muscle regeneration and force recovery. Muscle T2 assessed by MRI, a nonspecific marker of muscle damage, was significantly lower in IGF-1 injected, compared to contralateral soleus muscles at 2 and 5 days reambulation (P<0.05). The reduced prevalence of muscle damage in IGF-1 injected soleus muscles was confirmed on histology, with a lower fraction area of abnormal muscle tissue in IGF-I injected muscles at 2 days reambulation (33.2±3.3%vs 54.1±3.6%, P<0.05). Evidence of the effect of IGF-1 on muscle regeneration included timely increases in the number of central nuclei (21% at 5 days reambulation), paired-box transcription factor 7 (36% at 5 days), embryonic myosin (37% at 10 days), and elevated MyoD mRNA (7-fold at 2 days) in IGF-1 injected limbs (P<0.05). These findings demonstrate a potential role of IGF-1 in protecting unloaded

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

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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.

Does ankle joint power reflect type of muscle action of soleus and gastrocnemius during walking in cats and humans?

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Cronin, Neil J; Prilutsky, Boris I; Lichtwark, Glen A; Maas, Huub

2013-04-26

The main objective of this paper is to highlight the difficulties of identifying shortening and lengthening contractions based on analysis of power produced by resultant joint moments. For that purpose, we present net ankle joint powers and muscle fascicle/muscle-tendon unit (MTU) velocities for medial gastrocnemius (MG) and soleus (SO) muscles during walking in species of different size (humans and cats). For the cat, patterns of ankle joint power and MTU velocity of MG and SO during stance were similar: negative power (ankle moment×angular velocityankle joint power and fascicle velocity patterns were observed for MG muscle. In humans, like cats, the patterns of ankle joint power and MTU velocity of SO and MG were similar. Unlike the cat, there were substantial differences between patterns of fascicle velocity and ankle joint power during stance in both muscles. These results indicate that during walking, only a small fraction of mechanical work of the ankle moment is either generated or absorbed by the muscle fascicles, thus confirming the contribution of in-series elastic structures and/or energy transfer via two-joint muscles. We conclude that ankle joint negative power does not necessarily indicate eccentric action of muscle fibers and that positive power cannot be exclusively attributed to muscle concentric action, especially in humans. Copyright © 2013 Elsevier Ltd. All rights reserved.

Altered Satellite Cell Responsiveness and Denervation Implicated in Progression of Rotator-Cuff Injury.

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Deanna Gigliotti

Full Text Available Rotator-cuff injury (RCI is common and painful; even after surgery, joint stability and function may not recover. Relative contributions to atrophy from disuse, fibrosis, denervation, and satellite-cell responsiveness to activating stimuli are not known.Potential contributions of denervation and disrupted satellite cell responses to growth signals were examined in supraspinatus (SS and control (ipsilateral deltoid muscles biopsied from participants with RCI (N = 27. Biopsies were prepared for explant culture (to study satellite cell activity, immunostained to localize Pax7, BrdU, and Semaphorin 3A in satellite cells, sectioning to study blood vessel density, and western blotting to measure the fetal (γ subunit of acetylcholine receptor (γ-AchR. Principal component analysis (PCA for 35 parameters extracted components identified variables that contributed most to variability in the dataset. γ-AchR was higher in SS than control, indicating denervation. Satellite cells in SS had a low baseline level of activity (Pax7+ cells labelled in S-phase versus control; only satellite cells in SS showed increased proliferative activity after nitric oxide-donor treatment. Interestingly, satellite cell localization of Semaphorin 3A, a neuro-chemorepellent, was greater in SS (consistent with fiber denervation than control muscle at baseline. PCAs extracted components including fiber atrophy, satellite cell activity, fibrosis, atrogin-1, smoking status, vascular density, γAchR, and the time between symptoms and surgery. Use of deltoid as a control for SS was supported by PCA findings since "muscle" was not extracted as a variable in the first two principal components. SS muscle in RCI is therefore atrophic, denervated, and fibrotic, and has satellite cells that respond to activating stimuli.Since SS satellite cells can be activated in culture, a NO-donor drug combined with stretching could promote muscle growth and improve functional outcome after RCI. PCAs

Altered Satellite Cell Responsiveness and Denervation Implicated in Progression of Rotator-Cuff Injury.

Science.gov (United States)

Gigliotti, Deanna; Leiter, Jeff R S; MacDonald, Peter B; Peeler, Jason; Anderson, Judy E

Rotator-cuff injury (RCI) is common and painful; even after surgery, joint stability and function may not recover. Relative contributions to atrophy from disuse, fibrosis, denervation, and satellite-cell responsiveness to activating stimuli are not known. Potential contributions of denervation and disrupted satellite cell responses to growth signals were examined in supraspinatus (SS) and control (ipsilateral deltoid) muscles biopsied from participants with RCI (N = 27). Biopsies were prepared for explant culture (to study satellite cell activity), immunostained to localize Pax7, BrdU, and Semaphorin 3A in satellite cells, sectioning to study blood vessel density, and western blotting to measure the fetal (γ) subunit of acetylcholine receptor (γ-AchR). Principal component analysis (PCA) for 35 parameters extracted components identified variables that contributed most to variability in the dataset. γ-AchR was higher in SS than control, indicating denervation. Satellite cells in SS had a low baseline level of activity (Pax7+ cells labelled in S-phase) versus control; only satellite cells in SS showed increased proliferative activity after nitric oxide-donor treatment. Interestingly, satellite cell localization of Semaphorin 3A, a neuro-chemorepellent, was greater in SS (consistent with fiber denervation) than control muscle at baseline. PCAs extracted components including fiber atrophy, satellite cell activity, fibrosis, atrogin-1, smoking status, vascular density, γAchR, and the time between symptoms and surgery. Use of deltoid as a control for SS was supported by PCA findings since "muscle" was not extracted as a variable in the first two principal components. SS muscle in RCI is therefore atrophic, denervated, and fibrotic, and has satellite cells that respond to activating stimuli. Since SS satellite cells can be activated in culture, a NO-donor drug combined with stretching could promote muscle growth and improve functional outcome after RCI. PCAs suggest

Impact of C 60 fullerene on the dynamics of force-speed changes in soleus muscle of rat at ischemia-reperfusion injury.

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Nozdrenko, D M; Bogutska, K I; Prylutskyy, Yu I; Korolovych, V F; Evstigneev, M P; Ritter, U; Scharff, P

2015-01-01

The effect of C60 fullerene nanoparticles (30-90 nm) on dynamics of force response development to stimulated soleus muscle of rat with ischemic pathology, existing in muscle during the first 5 hours and first 5 days after 2 hours of ischemia and further reperfusion, was investigated using the tensometric method. It was found that intravenous and intramuscular administration of C60 fullerene with a single dose of 1 mg/kg exert different therapeutic effects dependent on the investigated macroparameters of muscle contraction. The intravenous drug administration was shown to be the most optimal for correction of the velocity macroparameters of contraction due to muscle tissue ischemic damage. In contrast, the intramuscular administration displays protective action with respect to motions associated with generation of maximal force response or continuous contractions elevating the level of muscle fatigue. Hence, C60 fullerene, being a strong antioxidant, may be considered as a promising agent for effective therapy of pathological states of the muscle system caused by pathological action of free radical processes.

Changes in soleus H-reflex during walking in middle-aged, healthy subjects

DEFF Research Database (Denmark)

Raffalt, Peter C; Alkjær, Tine; Simonsen, Erik B

2015-01-01

INTRODUCTION: To assess the effect of aging on stretch reflex modulation during walking, soleus H-reflexes obtained in 15 middle-aged (mean age 56.4±6.9 years) and 15 young (mean age 23.7±3.9 years) subjects were compared. METHODS: The H-reflex amplitude, muscle activity (EMG) of the soleus...... and tibialis anterior muscles, and EMG/H-reflex gain were measured during 4-km/h treadmill walking. RESULTS: The normalized H-reflex amplitude was lower in the swing phase for the middle-aged group, and there was no difference in muscle activity. EMG/H-reflex gain did not differ between groups. CONCLUSIONS: H......-reflex amplitude during walking was affected by aging, and changes during the swing phase could be seen in the middle-aged subjects. Subdividing the 2 age groups into groups of facilitated or suppressed swing-phase H-reflex revealed that the H-reflex amplitude modulation pattern in the group with facilitated swing...

Influence of different degrees of bilateral emulated contractures at the triceps surae on gait kinematics: The difference between gastrocnemius and soleus.

Science.gov (United States)

Attias, M; Bonnefoy-Mazure, A; De Coulon, G; Cheze, L; Armand, S

2017-10-01

Ankle plantarflexion contracture results from a permanent shortening of the muscle-tendon complex. It often leads to gait alterations. The objective of this study was to compare the kinematic adaptations of different degrees of contractures and between isolated bilateral gastrocnemius and soleus emulated contractures using an exoskeleton. Eight combinations of contractures were emulated bilaterally on 10 asymptomatic participants using an exoskeleton that was able to emulate different degrees of contracture of gastrocnemius (biarticular muscle) and soleus (monoarticular muscle), corresponding at 0°, 10°, 20°, and 30° ankle plantarflexion contracture (knee-flexed and knee-extended). Range of motion was limited by ropes attached for soleus on heel and below the knee and for gastrocnemius on heel and above the knee. A gait analysis session was performed to evaluate the effect of these different emulated contractures on the Gait Profile Score, walking speed and gait kinematics. Gastrocnemius and soleus contractures influence gait kinematics, with an increase of the Gait Profile Score. Significant differences were found in the kinematics of the ankles, knees and hips. Contractures of soleus cause a more important decrease in the range of motion at the ankle than the same degree of gastrocnemius contractures. Gastrocnemius contractures cause greater knee flexion (during the stance phase) and hip flexion (during all the gait cycle) than the same level of soleus contractures. These results can support the interpretation of the Clinical Gait Analysis data by providing a better understanding of the effect of isolate contracture of soleus and gastrocnemius on gait kinematics. Copyright © 2017 Elsevier B.V. All rights reserved.

Acute Gastrocnemius-Soleus Complex Injuries in National Football League Athletes

OpenAIRE

Werner, Brian C.; Belkin, Nicole S.; Kennelly, Steve; Weiss, Leigh; Barnes, Ronnie P.; Potter, Hollis G.; Warren, Russell F.; Rodeo, Scott A.

2017-01-01

Background: Lower extremity muscle injuries are common in professional football. Although less common than hamstring or quadriceps injuries in National Football League (NFL) athletes, calf injuries occur with relative frequency and have not previously been studied. Purpose: To evaluate gastrocnemius-soleus complex muscle injuries over the past 13 years from a single NFL team to determine the incidence of such injuries, their imaging characteristics, and return to play after such injuries and ...

The response of denervated muscle to long-term stimulation (1985, revisited here in 2014

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Terje Lomo

2014-03-01

Full Text Available In 1985, at a meeting in Abano, I presented results showing that direct stimulation of skeletal muscles with appropriate stimulus patterns prevents the effects of denervation on non-junctional properties of muscle fibers. Hence, it appeared unnecessary to postulate that unknown nerve-derived trophic factors control such properties, as posited by the (anterograde neurotrophic hypothesis. Here I discuss this conclusion in the light of what we know today, particularly with respect to the many lines of evidence that were then taken to support the trophic hypothesis, but which today have alternative interpretations consistent with control by evoked impulse activity. Despite much effort, no one has yet identified any nerve-derived factor consistent with the neurotrophic hypothesis. Reports favoring the existence of neurotrophic factors were numerous before 2000. Now they have essentially disappeared from the literature, including original research papers, textbooks and handbooks, suggesting that the hypothesis is no longer arguable. Thus, the results that I presented in our paper in 1985 seem to have held up rather well.

Basal and insulin-stimulated skeletal muscle sugar transport in endotoxic and bacteremic rats

International Nuclear Information System (INIS)

Westfall, M.V.; Sayeed, M.M.

1988-01-01

Membrane glucose transport with and without insulin was studied in soleus muscle from 5-h endotoxic rats (40 mg/kg Salmonella enteritidis lipopolysaccharide), and in soleus and epitrochlearis muscles from 12-h bacteremic (Escherichia coli, 4 X 10(10) CFU/kg) rats. Glucose transport was measured in muscles by evaluating the fractional efflux of 14 C-labeled 3-O-methylglucose ( 14 C-3-MG) after loading muscles with 14 C-3-MG. Basal 3-MG transport was elevated in soleus muscles from endotoxic as well as in soleus and epitrochlearis muscles from bacteremic rats compared with time-matched controls. Low insulin concentrations stimulated 14 C-3-MG transport more in bacteremic and endotoxic rat muscles than in controls. However, sugar transport in the presence of high insulin dose was attenuated in soleus and epitrochlearis muscles from bacteremic rats and soleus muscles from endotoxic rats compared with controls. Analysis of the dose-response relationship with ALLFIT revealed that the maximal transport response to insulin was significantly decreased in both models of septic shock. Sensitivity to insulin (EC50) was increased in endotoxic rat muscles, and a somewhat similar tendency was observed in bacteremic rat soleus muscles. Neural and humoral influences and/or changes in cellular metabolic energy may contribute to the increase in basal transport. Shifts in insulin-mediated transport may be due to alterations in insulin-receptor-effector coupling and/or the number of available glucose transporters

Effects of hyperthyroidism and hypothyroidism on glutamine metabolism by skeletal muscle of the rat.

Science.gov (United States)

Parry-Billings, M; Dimitriadis, G D; Leighton, B; Bond, J; Bevan, S J; Opara, E; Newsholme, E A

1990-01-01

1. The effects of hyperthyroidism and hypothyroidism on the concentrations of glutamine and other amino acids in the muscle and plasma and on the rates of glutamine and alanine release from incubated isolated stripped soleus muscle of the rat were investigated. 2. Hyperthyroidism decreased the concentration of glutamine in soleus muscle but was without effect on that in the gastrocnemius muscle or in the plasma. Hyperthyroidism also increased markedly the rate of release of glutamine from the incubated soleus muscle. 3. Hypothyroidism decreased the concentrations of glutamine in the gastrocnemius muscle and plasma but was without effect on that in soleus muscle. Hypothyroidism also decreased markedly the rate of glutamine release from the incubated soleus muscle. 4. Thyroid status was found to have marked effects on the rate of glutamine release by skeletal muscle per se, and may be important in the control of this process in both physiological and pathological conditions. PMID:2268261

Calf muscle volume estimates: Implications for Botulinum toxin treatment?

DEFF Research Database (Denmark)

Bandholm, Thomas; Sonne-Holm, Stig; Thomsen, Carsten

2007-01-01

An optimal botulinum toxin dose may be related to the volume of the targeted muscle. We investigated the suitability of using ultrasound and anthropometry to estimate gastrocnemius and soleus muscle volume. Gastrocnemius and soleus muscle thickness was measured in 11 cadaveric human legs, using...

Activation of plantar flexor muscles is constrained by multiple muscle synergies rather than joint torques.

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Takahito Suzuki

Full Text Available Behavioral evidence has suggested that a small number of muscle synergies may be responsible for activating a variety of muscles. Nevertheless, such dimensionality reduction may also be explained using the perspective of alternative hypotheses, such as predictions based on linear combinations of joint torques multiplied by corresponding coefficients. To compare the explanatory capacity of these hypotheses for describing muscle activation, we enrolled 12 male volunteers who performed isometric plantar flexor contractions at 10-100% of maximum effort. During each plantar flexor contraction, the knee extensor muscles were isometrically contracted at 0%, 50%, or 100% of maximum effort. Electromyographic activity was recorded from the vastus lateralis, medial gastrocnemius (MG, lateral gastrocnemius (LG, and soleus muscles and quantified using the average rectified value (ARV. At lower plantar flexion torque, regression analysis identified a clear linear relationship between the MG and soleus ARVs and between the MG and LG ARVs, suggesting the presence of muscle synergy (r2 > 0.65. The contraction of the knee extensor muscles induced a significant change in the slope of this relationship for both pairs of muscles (MG × soleus, P = 0.002; MG × LG, P = 0.006. Similarly, the slope of the linear relationship between the plantar flexion torque and the ARV of the MG or soleus changed significantly with knee extensor contraction (P = 0.031 and P = 0.041, respectively. These results suggest that muscle synergies characterized by non-mechanical constraints are selectively recruited according to whether contraction of the knee extensor muscles is performed simultaneously, which is relatively consistent with the muscle synergy hypothesis.

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.

Key Markers of mTORC1-Dependent and mTORC1-Independent Signaling Pathways Regulating Protein Synthesis in Rat Soleus Muscle During Early Stages of Hindlimb Unloading.

Science.gov (United States)

Mirzoev, Timur; Tyganov, Sergey; Vilchinskaya, Natalia; Lomonosova, Yulia; Shenkman, Boris

2016-01-01

The purpose of the study was to assess the amount of rRNA and phosphorylation status of the key markers of mTORC1-dependent (70s6k, 4E-BP1) and mTORC1-independent (GSK-3β, AMPK) signaling pathways controlling protein synthesis in rat soleus during early stages of mechanical unloading (hindlimb suspension (HS) for 1-, 3- and 7 days). The content of the key signaling molecules of various anabolic signaling pathways was determined by Western-blotting. The amount of 28S rRNA was evaluated by RT-PCR. The rate of protein synthesis was assessed using in-vivo SUnSET technique. HS for 3 and 7 days induced a significant (pprotein synthesis in soleus muscle in comparison with control. HS within 24 hours resulted in a significant (pprotein synthesis in rat soleus during early stages of simulated microgravity is associated with impaired ribosome biogenesis as well as reduced activity of mTORC1-independent signaling pathways. © 2016 The Author(s) Published by S. Karger AG, Basel.

Impaired macrophage and satellite cell infiltration occurs in a muscle-specific fashion following injury in diabetic skeletal muscle.

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Matthew P Krause

Full Text Available Systemic elevations in PAI-1 suppress the fibrinolytic pathway leading to poor collagen remodelling and delayed regeneration of tibialis anterior (TA muscles in type-1 diabetic Akita mice. However, how impaired collagen remodelling was specifically attenuating regeneration in Akita mice remained unknown. Furthermore, given intrinsic differences between muscle groups, it was unclear if the reparative responses between muscle groups were different.Here we reveal that diabetic Akita muscles display differential regenerative responses with the TA and gastrocnemius muscles exhibiting reduced regenerating myofiber area compared to wild-type mice, while soleus muscles displayed no difference between animal groups following injury. Collagen levels in TA and gastrocnemius, but not soleus, were significantly increased post-injury versus controls. At 5 days post-injury, when degenerating/necrotic regions were present in both animal groups, Akita TA and gastrocnemius muscles displayed reduced macrophage and satellite cell infiltration and poor myofiber formation. By 10 days post-injury, necrotic regions were absent in wild-type TA but persisted in Akita TA. In contrast, Akita soleus exhibited no impairment in any of these measures compared to wild-type soleus. In an effort to define how impaired collagen turnover was attenuating regeneration in Akita TA, a PAI-1 inhibitor (PAI-039 was orally administered to Akita mice following cardiotoxin injury. PAI-039 administration promoted macrophage and satellite cell infiltration into necrotic areas of the TA and gastrocnemius. Importantly, soleus muscles exhibit the highest inducible expression of MMP-9 following injury, providing a mechanism for normative collagen degradation and injury recovery in this muscle despite systemically elevated PAI-1.Our findings suggest the mechanism underlying how impaired collagen remodelling in type-1 diabetes results in delayed regeneration is an impairment in macrophage

The relationship between exercise-induced muscle fatigue, arterial blood flow and muscle perfusion after 56 days local muscle unloading.

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Weber, Tobias; Ducos, Michel; Mulder, Edwin; Beijer, Åsa; Herrera, Frankyn; Zange, Jochen; Degens, Hans; Bloch, Wilhelm; Rittweger, Jörn

2014-05-01

In the light of the dynamic nature of habitual plantar flexor activity, we utilized an incremental isokinetic exercise test (IIET) to assess the work-related power deficit (WoRPD) as a measure for exercise-induced muscle fatigue before and after prolonged calf muscle unloading and in relation to arterial blood flow and muscle perfusion. Eleven male subjects (31 ± 6 years) wore the HEPHAISTOS unloading orthosis unilaterally for 56 days. It allows habitual ambulation while greatly reducing plantar flexor activity and torque production. Endpoint measurements encompassed arterial blood flow, measured in the femoral artery using Doppler ultrasound, oxygenation of the soleus muscle assessed by near-infrared spectroscopy, lactate concentrations determined in capillary blood and muscle activity using soleus muscle surface electromyography. Furthermore, soleus muscle biopsies were taken to investigate morphological muscle changes. After the intervention, maximal isokinetic torque was reduced by 23·4 ± 8·2% (Pflow, tissue oxygenation, lactate concentrations and EMG median frequency kinematics during the exercise test were comparable before and after the intervention, whereas the increase of RMS in response to IIET was less following the intervention (P = 0·03). In conclusion, following submaximal isokinetic muscle work exercise-induced muscle fatigue is unaffected after prolonged local muscle unloading. The observation that arterial blood flow was maintained may underlie the unchanged fatigability. © 2013 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

Adaptation of Mouse Skeletal Muscle to Long-Term Microgravity in the MDS Mission

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Camerino, Giulia M.; Bianchini, Elisa; Ciciliot, Stefano; Danieli-Betto, Daniela; Dobrowolny, Gabriella; Furlan, Sandra; Germinario, Elena; Goto, Katsumasa; Gutsmann, Martina; Kawano, Fuminori; Nakai, Naoya; Ohira, Takashi; Ohno, Yoshitaka; Picard, Anne; Salanova, Michele; Schiffl, Gudrun; Blottner, Dieter; Musarò, Antonio; Ohira, Yoshinobu; Betto, Romeo; Conte, Diana; Schiaffino, Stefano

2012-01-01

The effect of microgravity on skeletal muscles has so far been examined in rat and mice only after short-term (5–20 day) spaceflights. The mice drawer system (MDS) program, sponsored by Italian Space Agency, for the first time aimed to investigate the consequences of long-term (91 days) exposure to microgravity in mice within the International Space Station. Muscle atrophy was present indistinctly in all fiber types of the slow-twitch soleus muscle, but was only slightly greater than that observed after 20 days of spaceflight. Myosin heavy chain analysis indicated a concomitant slow-to-fast transition of soleus. In addition, spaceflight induced translocation of sarcolemmal nitric oxide synthase-1 (NOS1) into the cytosol in soleus but not in the fast-twitch extensor digitorum longus (EDL) muscle. Most of the sarcolemmal ion channel subunits were up-regulated, more in soleus than EDL, whereas Ca2+-activated K+ channels were down-regulated, consistent with the phenotype transition. Gene expression of the atrophy-related ubiquitin-ligases was up-regulated in both spaceflown soleus and EDL muscles, whereas autophagy genes were in the control range. Muscle-specific IGF-1 and interleukin-6 were down-regulated in soleus but up-regulated in EDL. Also, various stress-related genes were up-regulated in spaceflown EDL, not in soleus. Altogether, these results suggest that EDL muscle may resist to microgravity-induced atrophy by activating compensatory and protective pathways. Our study shows the extended sensitivity of antigravity soleus muscle after prolonged exposition to microgravity, suggests possible mechanisms accounting for the resistance of EDL, and individuates some molecular targets for the development of countermeasures. PMID:22470446

Adaptation of mouse skeletal muscle to long-term microgravity in the MDS mission.

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Dorianna Sandonà

Full Text Available The effect of microgravity on skeletal muscles has so far been examined in rat and mice only after short-term (5-20 day spaceflights. The mice drawer system (MDS program, sponsored by Italian Space Agency, for the first time aimed to investigate the consequences of long-term (91 days exposure to microgravity in mice within the International Space Station. Muscle atrophy was present indistinctly in all fiber types of the slow-twitch soleus muscle, but was only slightly greater than that observed after 20 days of spaceflight. Myosin heavy chain analysis indicated a concomitant slow-to-fast transition of soleus. In addition, spaceflight induced translocation of sarcolemmal nitric oxide synthase-1 (NOS1 into the cytosol in soleus but not in the fast-twitch extensor digitorum longus (EDL muscle. Most of the sarcolemmal ion channel subunits were up-regulated, more in soleus than EDL, whereas Ca(2+-activated K(+ channels were down-regulated, consistent with the phenotype transition. Gene expression of the atrophy-related ubiquitin-ligases was up-regulated in both spaceflown soleus and EDL muscles, whereas autophagy genes were in the control range. Muscle-specific IGF-1 and interleukin-6 were down-regulated in soleus but up-regulated in EDL. Also, various stress-related genes were up-regulated in spaceflown EDL, not in soleus. Altogether, these results suggest that EDL muscle may resist to microgravity-induced atrophy by activating compensatory and protective pathways. Our study shows the extended sensitivity of antigravity soleus muscle after prolonged exposition to microgravity, suggests possible mechanisms accounting for the resistance of EDL, and individuates some molecular targets for the development of countermeasures.

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

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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

Acute effects of high-frequency microfocal vibratory stimulation on the H reflex of the soleus muscle. A double-blind study in healthy subjects.

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Alfonsi, Enrico; Paone, Paolo; Tassorelli, Cristina; De Icco, Roberto; Moglia, Arrigo; Alvisi, Elena; Marchetta, Lucky; Fresia, Mauro; Montini, Alessandra; Calabrese, Marzia; Versiglia, Vittorio; Sandrini, Giorgio

2015-01-01

This study in healthy subjects examined the effects of a system delivering focal microvibrations at high frequency (Equistasi®) on tonic vibration stimulus (TVS)-induced inhibition of the soleus muscle H reflex. Highfrequency microvibrations significantly increased the inhibitory effect of TVS on the H reflex for up to three minutes. Moreover, Equistasi® also significantly reduced alpha-motoneuron excitability, as indicated by the changes in the ratio between the maximumamplitude H reflex (Hmax reflex) and the maximumamplitude muscle response (Mmax response); this effect was due to reduction of the amplitude of the H reflex because the amplitude of muscle response remained unchanged. The present findings indicate that Equistasi® has a modulatory effect on proprioceptive reflex circuits. Therefore, Equistasi® might interfere with some mechanisms involved in both physiological and pathophysiological control of movement and of posture.

Load rather than length sensitive feedback contributes to soleus muscle activity during human treadmill walking

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af Klint, Richard; Mazzaro, Nazarena; Nielsen, Jens Bo

2010-01-01

Walking requires a constant adaptation of locomotor output from sensory afferent feedback mechanisms to ensure efficient and stable gait. We investigated the nature of the sensory afferent feedback contribution to the soleus motoneuronal drive and to the corrective stretch reflex by manipulating...... on the soleus stretch reflex was measured by presenting dorsiflexion perturbations ( approximately 5 degrees, 360-400 degrees/s) in mid and late stances. Short (SLRs) and medium latency reflexes (MLRs) were quantified in a 15 ms analysis window. The MLR decreased with decreased loading (P = 0.......045), but no significant difference was observed for the SLR (P = 0.13). Similarly, the effect of the BWS was measured on the unload response, i.e., the depression in soleus activity following a plantar-flexion perturbation ( approximately 5.6 degrees, 203-247 degrees/s), quantified over a 50 ms analysis window...

Peripheral denervation participates in heterotopic ossification in a spinal cord injury model.

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Charlotte Debaud

Full Text Available We previously reported the development of a new acquired neurogenic HO (NHO mouse model, combining spinal cord transection (SCI and chemical muscle injury. Pathological mechanisms responsible for ectopic osteogenesis after central neurological damage are still to be elucidated. In this study, we first hypothesized that peripheral nervous system (PNS might convey pathological signals from injured spinal cord to muscles in NHO mouse model. Secondly, we sought to determine whether SCI could lead to intramuscular modifications of BMP2 signaling pathways. Twenty one C57Bl6 mice were included in this protocol. Bilateral cardiotoxin (CTX injection in hamstring muscles was associated with a two-stage surgical procedure, combining thoracic SCI with unilateral peripheral denervation. Volumes of HO (Bone Volume, BV were measured 28 days after surgery using micro-computed tomography imaging techniques and histological analyses were made to confirm intramuscular osteogenesis. Volume comparisons were conducted between right and left hind limb of each animal, using a Wilcoxon signed rank test. Quantitative polymerase chain reaction (qPCR was performed to explore intra muscular expression of BMP2, Alk3 and Id1. Nineteen mice survive the complete SCI and peripheral denervation procedure. When CTX injections were done right after surgery (n = 7, bilateral HO were detected in all animals after 28 days. Micro-CT measurements showed significantly increased BV in denervated paws (1.47 mm3 +/- 0.5 compared to contralateral sides (0.56 mm3 +/-0.4, p = 0.03. When peripheral denervation and CTX injections were performed after sham SCI surgery (n = 6, bilateral HO were present in three mice at day 28. Quantitative PCR analyses showed no changes in intra muscular BMP2 expression after SCI as compared to control mice (shamSCI. Peripheral denervation can be reliably added to spinal cord transection in NHO mouse model. This new experimental design confirms that neuro

Subacute mandibular and hypoglossal nerve denervation causing oedema of the masticator space and tongue

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Ho, T.; Lee, K.; Lee, H.

2003-01-01

We report the MRI of five patients with denervation oedema in the head and neck. Four had denervation oedema in one masticator space caused by a skull-base tumour invading the ipsilateral foramen ovale. Another case had denervation oedema confined to the half of the tongue ipsilateral to oral reconstruction surgery which involved mandibulectomy, free flap repair and wide excision of a buccal mucosal carcinoma. Inversion-recovery and/or T2-weighted spin-echo images showed increased signal in the affected areas. Contrast-enhanced T1-weighted images revealed enhancement of the muscles. There was no evidence of tumour or infection in the masticator space or tongue. It is important to differentiate denervation oedema from other disease processes causing high signal on T2-weighted images, such as tumour infiltration and soft-tissue infection. (orig.)

Test-retest reliability of the soleus H-reflex excitability measured during human walking

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Simonsen, Erik B; Dyhre-Poulsen, Poul

2010-01-01

The purpose of the study was to investigate with what accuracy the soleus H-reflex modulation and excitability could be measured during human walking on two occasions separated by days. The maximal M-wave (Mmax) was measured at rest in the standing position. During treadmill walking every stimulus...... elicited an M-wave of 25+/-10% of Mmax in the soleus muscle and a supra-maximal stimulus elicited a maximal M-wave 60ms after the first stimulus. Both Mmax during rest and during walking were later used for normalization. When normalized to resting Mmax, the peak reflex amplitude during walking was 5...

Regional thermal specialisation in a mammal: temperature affects power output of core muscle more than that of peripheral muscle in adult mice (Mus musculus).

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James, Rob S; Tallis, Jason; Angilletta, Michael J

2015-01-01

In endotherms, such as mammals and birds, internal organs can specialise to function within a narrow thermal range. Consequently, these organs should become more sensitive to changes in body temperature. Yet, organs at the periphery of the body still experience considerable fluctuations in temperature, which could select for lower thermal sensitivity. We hypothesised that the performance of soleus muscle taken from the leg would depend less on temperature than would the performance of diaphragm muscle taken from the body core. Soleus and diaphragm muscles were isolated from mice and subjected to isometric and work-loop studies to analyse mechanical performance at temperatures between 15 and 40 °C. Across this thermal range, soleus muscle took longer to generate isometric force and longer to relax, and tended to produce greater normalised maximal force (stress) than did diaphragm muscle. The time required to produce half of maximal force during isometric tetanus and the time required to relax half of maximal force were both more sensitive to temperature in soleus than they were in diaphragm. However, thermal sensitivities of maximal force during isometric tetani were similar for both muscles. Consistent with our hypothesis, power output (the product of speed and force) was greater in magnitude and more thermally sensitive in diaphragm than it was in soleus. Our findings, when combined with previous observations of muscles from regionally endothermic fish, suggest that endothermy influences the thermal sensitivities of power output in core and peripheral muscles.

Short-term locomotor adaptation to a robotic ankle exoskeleton does not alter soleus Hoffmann reflex amplitude.

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Kao, Pei-Chun; Lewis, Cara L; Ferris, Daniel P

2010-07-26

To improve design of robotic lower limb exoskeletons for gait rehabilitation, it is critical to identify neural mechanisms that govern locomotor adaptation to robotic assistance. Previously, we demonstrated soleus muscle recruitment decreased by approximately 35% when walking with a pneumatically-powered ankle exoskeleton providing plantar flexor torque under soleus proportional myoelectric control. Since a substantial portion of soleus activation during walking results from the stretch reflex, increased reflex inhibition is one potential mechanism for reducing soleus recruitment when walking with exoskeleton assistance. This is clinically relevant because many neurologically impaired populations have hyperactive stretch reflexes and training to reduce the reflexes could lead to substantial improvements in their motor ability. The purpose of this study was to quantify soleus Hoffmann (H-) reflex responses during powered versus unpowered walking. We tested soleus H-reflex responses in neurologically intact subjects (n=8) that had trained walking with the soleus controlled robotic ankle exoskeleton. Soleus H-reflex was tested at the mid and late stance while subjects walked with the exoskeleton on the treadmill at 1.25 m/s, first without power (first unpowered), then with power (powered), and finally without power again (second unpowered). We also collected joint kinematics and electromyography. When the robotic plantar flexor torque was provided, subjects walked with lower soleus electromyographic (EMG) activation (27-48%) and had concomitant reductions in H-reflex amplitude (12-24%) compared to the first unpowered condition. The H-reflex amplitude in proportion to the background soleus EMG during powered walking was not significantly different from the two unpowered conditions. These findings suggest that the nervous system does not inhibit the soleus H-reflex in response to short-term adaption to exoskeleton assistance. Future studies should determine if the

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

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Tomoki Abe

2013-01-01

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

Tetanic contraction induces enhancement of fatigability and sarcomeric damage in atrophic skeletal muscle and its underlying molecular mechanisms.

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Yu, Zhi-Bin

2013-11-01

Muscle unloading due to long-term exposure of weightlessness or simulated weightlessness causes atrophy, loss of functional capacity, impaired locomotor coordination, and decreased resistance to fatigue in the antigravity muscles of the lower limbs. Besides reducing astronauts' mobility in space and on returning to a gravity environment, the molecular mechanisms for the adaptation of skeletal muscle to unloading also play an important medical role in conditions such as disuse and paralysis. The tail-suspended rat model was used to simulate the effects of weightlessness on skeletal muscles and to induce muscle unloading in the rat hindlimb. Our series studies have shown that the maximum of twitch tension and the twitch duration decreased significantly in the atrophic soleus muscles, the maximal tension of high-frequency tetanic contraction was significantly reduced in 2-week unloaded soleus muscles, however, the fatigability of high-frequency tetanic contraction increased after one week of unloading. The maximal isometric tension of intermittent tetanic contraction at optimal stimulating frequency did not alter in 1- and 2-week unloaded soleus, but significantly decreased in 4-week unloaded soleus. The 1-week unloaded soleus, but not extensor digitorum longus (EDL), was more susceptible to fatigue during intermittent tetanic contraction than the synchronous controls. The changes in K+ channel characteristics may increase the fatigability during high-frequency tetanic contraction in atrophic soleus muscles. High fatigability of intermittent tetanic contraction may be involved in enhanced activity of sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) and switching from slow to fast isoform of myosin heavy chain, tropomyosin, troponin I and T subunit in atrophic soleus muscles. Unloaded soleus muscle also showed a decreased protein level of neuronal nitric oxide synthase (nNOS), and the reduction in nNOS-derived NO increased frequency of calcium sparks and elevated

Cancer cachexia decreases specific force and accelerates fatigue in limb muscle

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

2013-06-07

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

Cancer cachexia decreases specific force and accelerates fatigue in limb muscle

International Nuclear Information System (INIS)

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

2013-01-01

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

Long-Term Chronic Intermittent Hypobaric Hypoxia Induces Glucose Transporter (GLUT4 Translocation Through AMP-Activated Protein Kinase (AMPK in the Soleus Muscle in Lean Rats

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Patricia Siques

2018-06-01

Full Text Available Background: In chronic hypoxia (CH and short-term chronic intermittent hypoxia (CIH exposure, glycemia and insulin levels decrease and insulin sensitivity increases, which can be explained by changes in glucose transport at skeletal muscles involving GLUT1, GLUT4, Akt, and AMPK, as well as GLUT4 translocation to cell membranes. However, during long-term CIH, there is no information regarding whether these changes occur similarly or differently than in other types of hypoxia exposure. This study evaluated the levels of AMPK and Akt and the location of GLUT4 in the soleus muscles of lean rats exposed to long-term CIH, CH, and normoxia (NX and compared the findings.Methods: Thirty male adult rats were randomly assigned to three groups: a NX (760 Torr group (n = 10, a CIH group (2 days hypoxia/2 days NX; n = 10 and a CH group (n = 10. Rats were exposed to hypoxia for 30 days in a hypobaric chamber set at 428 Torr (4,600 m. Feeding (10 g daily and fasting times were accurately controlled. Measurements included food intake (every 4 days, weight, hematocrit, hemoglobin, glycemia, serum insulin (by ELISA, and insulin sensitivity at days 0 and 30. GLUT1, GLUT4, AMPK levels and Akt activation in rat soleus muscles were determined by western blot. GLUT4 translocation was measured with confocal microscopy at day 30.Results: (1 Weight loss and increases in hematocrit and hemoglobin were found in both hypoxic groups (p < 0.05. (2 A moderate decrease in glycemia and plasma insulin was found. (3 Insulin sensitivity was greater in the CIH group (p < 0.05. (4 There were no changes in GLUT1, GLUT4 levels or in Akt activation. (5 The level of activated AMPK was increased only in the CIH group (p < 0.05. (6 Increased GLUT4 translocation to the plasma membrane of soleus muscle cells was observed in the CIH group (p < 0.05.Conclusion: In lean rats experiencing long-term CIH, glycemia and insulin levels decrease and insulin sensitivity increases. Interestingly, there

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.

FIRST SOUND EVIDENCE OF MUSCLE REGENERATION IN RECOVERY OF FUNCTION OF HUMAN PERMANENT DENERVATED MUSCLES BY A LONG-LASTING FUNCTIONAL ELECTRICAL STIMULATION (FES TRAINING: BIOPSY FINDINGS

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Helmut Kern

2004-12-01

Full Text Available Contrary to general believe, in one case of 18month cauda equina lesion four-month electrical stimulation of thigh muscles (impulse energy 1.92 Joule increased stimulation frequency from 2 to 20 Hz, i. e., up to tetanic contractions. After 2 years of treatment, CT-cross sectional area of quadriceps improved 58.3% (right and 44.4% (left with increased muscle density. Mean myofiber size was 37.2 ± 24.8 µm (right and 40.5 ±  24.9 µm (left. Improvement of stimulated knee torque, from zero to 12.0 Nm and 10.5 Nm, respectively, enabled to stand up trials. Surviving myofibers undergo re-growth (they show the chess board appearance of normal muscle, and dying myofibers continuously regenerate (up to 3% are embryonic myosin positive 3-year post-FES. Regeneration events are essential components of the FES rehabilitation protocol due to superior excitability of regenerated myofibers in comparison to long-term denervated, degenerated myofibers, which were almost not excitable before FES training.

Is Soleus Muscle-Tendon-Unit Behavior Related to Ground-Force Application During the Sprint Start?

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Schrödter, Erik; Brüggemann, Gert-Peter; Willwacher, Steffen

2017-04-01

To describe the stretch-shortening behavior of ankle plantar-flexing muscle-tendon units (MTUs) during the push-off in a sprint start. Fifty-four male (100-m personal best: 9.58-12.07 s) and 34 female (100-m personal best: 11.05-14.00 s) sprinters were analyzed using an instrumented starting block and 2-dimensional high-speed video imaging. Analysis was performed separately for front and rear legs, while accounting for block obliquities and performance levels. The results showed clear signs of a dorsiflexion in the upper ankle joint (front block 15.8° ± 7.4°, 95% CI 13.2-18.2°; rear block 8.0° ± 5.7°, 95% CI 6.4-9.7°) preceding plantar flexion. When observed in their natural block settings, the athletes' block obliquity did not significantly affect push-off characteristics. It seems that the stretch-shortening-cycle-like motion of the soleus MTU has an enhancing influence on push-off force generation. This study provides the first systematic observation of ankle-joint stretch-shortening behavior for sprinters of a wide range of performance levels. The findings highlight the importance of reactive-type training for the improvement of starting performance. Nonetheless, future studies need to resolve the independent contributions of tendinous and muscle-fascicle structures to overall MTU performance.

Muscle-specific expression of hypoxia-inducible factor in human skeletal muscle

DEFF Research Database (Denmark)

Mounier, Rémi; Pedersen, Bente Klarlund; Plomgaard, Peter

2010-01-01

fibres that possess unique patterns of protein and gene expression, producing different capillarization and energy metabolism systems. In this work, we analysed HIF-1alpha mRNA and protein expression related to the fibre-type composition in untrained human skeletal muscle by obtaining muscle biopsies...... from triceps brachii (characterized by a high proportion of type II fibres), from soleus (characterized by a high proportion of type I fibres) and from vastus lateralis (characterized by an equal proportion of type I and II fibres). The hypothesis was that type I muscle fibres would have lower HIF-1......alpha protein level. Interestingly, none of the HIF-1alpha target genes, like the most studied angiogenic factor involved in muscle angiogenesis, vascular endothelial growth factor (VEGF), exhibited a muscle fibre-specific-related mRNA expression at rest in normoxia. However, soleus presented...

Heat production during contraction in skeletal muscle of hypothyroid mice

Energy Technology Data Exchange (ETDEWEB)

Leijendekker, W.J.; van Hardeveld, C.; Elzinga, G. (Free Univ., Amsterdam (Netherlands))

1987-08-01

The effect of hypothyroidism on tension-independent and -dependent heat produced during a twitch and a tetanic contraction of extensor digitorum longus (EDL) and soleus muscle of mice was examined. The amount of heat produced during a twitch and the rate of heat development during a tetanus of EDL and soleus were measured at and above optimal length. The effect of hypothyroidism on force production was <30%. Straight lines were used to fit the relation between heat production and force. Hypothyroidism significantly decreases tension-independent heat during contraction of EDL and soleus muscle. Because the tension-independent heat is considered to be related to the Ca{sup 2+} cycling, these findings suggest that ATP splitting due to the Ca{sup 2+} cycling is reduced in hypothyroid mice. This conclusion was strengthened by the observation that the oxalate-supported {sup 45}Ca{sup 2+}-uptake activity and {sup 45}Ca{sup 2+}-loading capacity of muscle homogenates from hypothyroid mice were reduced, respectively, to 51 and to 65% in soleus and to 63 and 73% in EDL muscle as compared with euthyroid mice. The tension-dependent rate of heat development during a tetanus was also decreased in soleus muscle of hypothyroid mice. This suggests a lower rate of ATP hydrolysis related to cross-bridge cycling in this muscle due to the hypothyroid state.

Renal sympathetic nervous system and the effects of denervation on renal arteries.

Science.gov (United States)

Kannan, Arun; Medina, Raul Ivan; Nagajothi, Nagapradeep; Balamuthusamy, Saravanan

2014-08-26

Resistant hypertension is associated with chronic activation of the sympathetic nervous system resulting in various comorbidities. The prevalence of resistant hypertension is often under estimated due to various reasons. Activation of sympathetic nervous system at the renal- as well as systemic- level contributes to the increased level of catecholamines and resulting increase in the blood pressure. This increased activity was demonstrated by increased muscle sympathetic nerve activity and renal and total body noradrenaline spillover. Apart from the hypertension, it is hypothesized to be associated with insulin resistance, congestive heart failure and obstructive sleep apnea. Renal denervation is a novel procedure where the sympathetic afferent and efferent activity is reduced by various techniques and has been used successfully to treat drug-resistant hypertension improvement of various metabolic derangements. Renal denervation has the unique advantage of offering the denervation at the renal level, thus mitigating the systemic side effects. Renal denervation can be done by various techniques including radiofrequency ablation, ultrasound guided ablation and chemical ablation. Various trials evaluated the role of renal denervation in the management of resistant hypertension and have found promising results. More studies are underway to evaluate the role of renal denervation in patients presenting with resistant hypertension in different scenarios. Appropriate patient selection might be the key in determining the effectiveness of the procedure.

Na+,K+-pump stimulation improves contractility in isolated muscles of mice with hyperkalemic periodic paralysis.

Science.gov (United States)

Clausen, Torben; Nielsen, Ole Bækgaard; Clausen, Johannes D; Pedersen, Thomas Holm; Hayward, Lawrence J

2011-07-01

In patients with hyperkalemic periodic paralysis (HyperKPP), attacks of muscle weakness or paralysis are triggered by K(+) ingestion or rest after exercise. Force can be restored by muscle work or treatment with β(2)-adrenoceptor agonists. A missense substitution corresponding to a mutation in the skeletal muscle voltage-gated Na(+) channel (Na(v)1.4, Met1592Val) causing human HyperKPP was targeted into the mouse SCN4A gene (mutants). In soleus muscles prepared from these mutant mice, twitch, tetanic force, and endurance were markedly reduced compared with soleus from wild type (WT), reflecting impaired excitability. In mutant soleus, contractility was considerably more sensitive than WT soleus to inhibition by elevated [K(+)](o). In resting mutant soleus, tetrodotoxin (TTX)-suppressible (22)Na uptake and [Na(+)](i) were increased by 470 and 58%, respectively, and membrane potential was depolarized (by 16 mV, P Na(+),K(+) pump-mediated (86)Rb uptake was 83% larger than in WT. Salbutamol stimulated (86)Rb uptake and reduced [Na(+)](i) both in mutant and WT soleus. Stimulating Na(+),K(+) pumps with salbutamol restored force in mutant soleus and extensor digitorum longus (EDL). Increasing [Na(+)](i) with monensin also restored force in soleus. In soleus, EDL, and tibialis anterior muscles of mutant mice, the content of Na(+),K(+) pumps was 28, 62, and 33% higher than in WT, respectively, possibly reflecting the stimulating effect of elevated [Na(+)](i) on the synthesis of Na(+),K(+) pumps. The results confirm that the functional disorders of skeletal muscles in HyperKPP are secondary to increased Na(+) influx and show that contractility can be restored by acute stimulation of the Na(+),K(+) pumps. Calcitonin gene-related peptide (CGRP) restored force in mutant soleus but caused no detectable increase in (86)Rb uptake. Repeated excitation and capsaicin also restored contractility, possibly because of the release of endogenous CGRP from nerve endings in the isolated

Effect of a 17 day spaceflight on contractile properties of human soleus muscle fibres

Science.gov (United States)

Widrick, J. J.; Knuth, S. T.; Norenberg, K. M.; Romatowski, J. G.; Bain, J. L.; Riley, D. A.; Karhanek, M.; Trappe, S. W.; Trappe, T. A.; Costill, D. L.;

Spatial facilitation of reciprocal inhibition and crossed inhibitory responses to soleus motoneurons during walking

DEFF Research Database (Denmark)

Stevenson, Andrew James Thomas; Geertsen, Svend Sparre; Nielsen, Jens Bo

2016-01-01

In humans, short-latency crossed spinal inhibitory reflexes are elicited in the contralateral soleus (cSOL) muscle following stimulation of the ipsilateral posterior tibial nerve (iPTN). To date, the spinal interneurons mediating the cSOL inhibition are unknown. This study investigated whether...

Heat production during contraction in skeletal muscle of hypothyroid mice

International Nuclear Information System (INIS)

Leijendekker, W.J.; van Hardeveld, C.; Elzinga, G.

1987-01-01

The effect of hypothyroidism on tension-independent and -dependent heat produced during a twitch and a tetanic contraction of extensor digitorum longus (EDL) and soleus muscle of mice was examined. The amount of heat produced during a twitch and the rate of heat development during a tetanus of EDL and soleus were measured at and above optimal length. The effect of hypothyroidism on force production was 2+ cycling, these findings suggest that ATP splitting due to the Ca 2+ cycling is reduced in hypothyroid mice. This conclusion was strengthened by the observation that the oxalate-supported 45 Ca 2+ -uptake activity and 45 Ca 2+ -loading capacity of muscle homogenates from hypothyroid mice were reduced, respectively, to 51 and to 65% in soleus and to 63 and 73% in EDL muscle as compared with euthyroid mice. The tension-dependent rate of heat development during a tetanus was also decreased in soleus muscle of hypothyroid mice. This suggests a lower rate of ATP hydrolysis related to cross-bridge cycling in this muscle due to the hypothyroid state

Degradation rate of acetylcholine receptors inserted into denervated vertebrate neuromuscular junctions

International Nuclear Information System (INIS)

Shyng, S.L.; Salpeter, M.M.

1989-01-01

Many studies exist on the effect of denervation on the degradation of acetylcholine receptors (AChRs) at the vertebrate neuromuscular junction (nmj). These studies have described the behavior of either the total population of junctional receptors at different times after denervation, or of the receptors present at the time of denervation. No experimental studies yet exist on the degradation rate of the receptors newly inserted into denervated junctions. In the previous studies, the original receptors of mouse sternomastoid muscles were found to retain the slow degradation (t 1/2) of approximately 8-10 d of innervated junctional receptors for up to 10 d after denervation before accelerating to a t 1/2 of approximately 3 d. The total junctional receptors, on the other hand, showed a progressive increase in degradation rate from a t 1/2 of 8-10 d to a t 1/2 of 1 d. To reconcile these earlier observations, the present study examines the degradation of new receptors inserted into the nmj after denervation. To avoid possible contamination of the data with postdenervation extrajunctional receptors, we used transmission electron microscope autoradiography to study only receptors located at the postjunctional fold of the nmj. We established that the new receptors inserted into denervated junctions have a t 1/2 of approximately 1 d, considerably faster than that of the original receptors and equivalent to that of postdenervation extrajunctional receptors. Both original and new receptors are interspersed at the top of the junctional folds. Thus, until all the original receptors are degraded, the postjunctional membrane contains two populations of AChRs that maintain a total steady-state site density but degrade at different rates

Side-To-Side Nerve Bridges Support Donor Axon Regeneration Into Chronically Denervated Nerves and Are Associated With Characteristic Changes in Schwann Cell Phenotype.

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Hendry, J Michael; Alvarez-Veronesi, M Cecilia; Snyder-Warwick, Alison; Gordon, Tessa; Borschel, Gregory H

2015-11-01

Chronic denervation resulting from long nerve regeneration times and distances contributes greatly to suboptimal outcomes following nerve injuries. Recent studies showed that multiple nerve grafts inserted between an intact donor nerve and a denervated distal recipient nerve stump (termed "side-to-side nerve bridges") enhanced regeneration after delayed nerve repair. To examine the cellular aspects of axon growth across these bridges to explore the "protective" mechanism of donor axons on chronically denervated Schwann cells. In Sprague Dawley rats, 3 side-to-side nerve bridges were placed over a 10-mm distance between an intact donor tibial (TIB) nerve and a recipient denervated common peroneal (CP) distal nerve stump. Green fluorescent protein-expressing TIB axons grew across the bridges and were counted in cross section after 4 weeks. Immunofluorescent axons and Schwann cells were imaged over a 4-month period. Denervated Schwann cells dedifferentiated to a proliferative, nonmyelinating phenotype within the bridges and the recipient denervated CP nerve stump. As donor TIB axons grew across the 3 side-to-side nerve bridges and into the denervated CP nerve, the Schwann cells redifferentiated to the myelinating phenotype. Bridge placement led to an increased mass of hind limb anterior compartment muscles after 4 months of denervation compared with muscles whose CP nerve was not "protected" by bridges. This study describes patterns of donor axon regeneration and myelination in the denervated recipient nerve stump and supports a mechanism where these donor axons sustain a proregenerative state to prevent deterioration in the face of chronic denervation.

Voluntary activation of ankle muscles is accompanied by subcortical facilitation of their antagonists

DEFF Research Database (Denmark)

Geertsen, Svend S.; Zuur, Abraham Theodoor; Nielsen, Jens B.

2010-01-01

Flexion and extension movements are organized reciprocally, so that extensor motoneurones in the spinal cord are inhibited when flexor muscles are active and vice versa. During and just prior to dorsiflexion of the ankle, soleus motoneurones are thus inhibited as evidenced by a depression......) or soleus muscle of the left ankle. TMS was applied to the hotspot of TA and soleus muscles on separate days. Stimuli were delivered prior to and at the beginning of contraction. Soleus MEPs were significantly facilitated when TMS was applied 50 ms prior to onset of plantar flexion. Surprisingly, soleus...... was increased prior to plantar flexion, but not prior to dorsiflexion. These findings suggest that voluntary contraction at the ankle is accompanied by preceding facilitation of antagonists by a subcortical motor programme. This may help to ensure that the direction of movement may be changed quickly...

Effects of long-duration bed rest on structural compartments of m. soleus in man

Science.gov (United States)

Belozerova, I.; Shenkman, B.; Mazin, M.; Leblanc, A.; LeBlanc, A. D. (Principal Investigator)

2001-01-01

Magnetic resonance imaging (MRI), histomorphometry and electron microscopy of muscle demonstrate that long-term exposure to actual or simulated weightlessness (including head down bed rest) leads to decreased volume of antigravity muscles in mammals. In muscles interbundle space is occupied by the connective tissue. Rat studies show that hindlimb unloading induces muscle fiber atrophy along with increase in muscle non-fiber connective tissue compartment. Beside that, usually 20% of the muscle fiber volume is comprised by non-contractile (non-myofibrillar) compartment. The aim of the present study was to compare changes in muscle volume, and in muscle fiber size with alterations in myofibrillar apparatus, and in connective tissue compartment in human m. soleus under conditions of 120 day long head down bed rest (HDBR).

Musculus soleus of rats at physical activity and L-carnitine and creatine phosphate effect

Directory of Open Access Journals (Sweden)

Irina A. Khutorskaya

2017-09-01

Full Text Available Introduction: The study of the effect of metabolic drugs on the histochemical characteristics of soleus muscle is relevant for solving the problem of providing the training process in Russia with non-doping drugs for safe correction of the consequences of intense physical activity in athletes. Materials and Methods: Dynamic physical activity in rats (n = 24 was simulated by swimming “to the limit” with weighting of 10 % of body weight (20 days, 1 time per day. The experimental animals were divided into four groups (6 animals each: № 1 – control, № 2 – swimming + isotonic NaCl solution, № 3 and № 4 – swimming + L-carnitine or creatine phosphate 100.0 mg/kg daily intraperitoneally. The object of the study was musculus soleus. Differentiation of muscle fibers was carried out by the intensity of histochemical activity of succinate dehydrogenase (SDG and alkaline stable adenosine triphosphate (ATP of myosin. The percentage of muscle fibers was evaluated and their diameter was defined by the direct morphometry. The obtained data were treated statistically by Student’s T-test. Results: Swimming of the animals “to the limit” do not affect the ratio of fibers with different phenotypes in the soleus muscle. This indicator is genetically determined and was not modified by L-carnitine and creatine phosphate. Dynamic physical activity promotes the development of hypertrophy of muscle fibers of various types. The investigated medicaments of the metabolic type either do not influence on the formation of exerciseinduced hypertrophy (predominantly creatine phosphate or reduce the intensity of the hypertrophic process (predominantly L-carnitine under dynamic physical activity. Discussion and Conclusions: The obtained data indicate L-carnitine and creatine phosphate do not have an anabolic effect. Taking into account the relevant data on ability of L-carnitine and creatine phosphate to effectively correct a negative effects of intensive

Magnetic resonance imaging of skeletal muscle in patients with Duchenne muscular dystrophy

International Nuclear Information System (INIS)

Nagao, Hideo; Morimoto, Takehiko; Sano, Nozomi; Takahashi, Mitsugi; Nagai, Hironao; Tawa, Ritsuko; Yoshimatsu, Makoto; Woo Young-Jong; Matsuda, Hiroshi.

1991-01-01

Magnetic resonance imaging of skeletal muscles in thirteen patients with Duchenne muscular dystrophy was performed to estimate pathological changes. Serial axial and sagittal sections of the right lower extremity were recorded. In the early stage, the T 1 values of gastrocnemius and soleus muscles were slightly lower than the control values, and in the late stage, the values were much lower in all muscles examined. In sagittal sections, the gastrocnemius muscle in the early stage showed a high density area at the distal region adjacent to soleus muscle, and the soleus muscle showed a high density area adjacent to the gestrocnemius muscle. In serial axial sections, high density areas of the anterior and posterior tibialis muscles appeared first at their proximal and peripheral regions. It was concluded that the sequence of appearance of pathological changes was different not only among individual muscles but also among various regions of each muscle; the high density changes appeared first at myotendon junctions. (author)

Adding Stiffness to the Foot Modulates Soleus Force-Velocity Behaviour during Human Walking

Science.gov (United States)

Takahashi, Kota Z.; Gross, Michael T.; van Werkhoven, Herman; Piazza, Stephen J.; Sawicki, Gregory S.

2016-07-01

Previous studies of human locomotion indicate that foot and ankle structures can interact in complex ways. The structure of the foot defines the input and output lever arms that influences the force-generating capacity of the ankle plantar flexors during push-off. At the same time, deformation of the foot may dissipate some of the mechanical energy generated by the plantar flexors during push-off. We investigated this foot-ankle interplay during walking by adding stiffness to the foot through shoes and insoles, and characterized the resulting changes in in vivo soleus muscle-tendon mechanics using ultrasonography. Added stiffness decreased energy dissipation at the foot (p < 0.001) and increased the gear ratio (i.e., ratio of ground reaction force and plantar flexor muscle lever arms) (p < 0.001). Added foot stiffness also altered soleus muscle behaviour, leading to greater peak force (p < 0.001) and reduced fascicle shortening speed (p < 0.001). Despite this shift in force-velocity behaviour, the whole-body metabolic cost during walking increased with added foot stiffness (p < 0.001). This increased metabolic cost is likely due to the added force demand on the plantar flexors, as walking on a more rigid foot/shoe surface compromises the plantar flexors’ mechanical advantage.

Calpain-mediated proteolysis of tropomodulin isoforms leads to thin filament elongation in dystrophic skeletal muscle.

Science.gov (United States)

Gokhin, David S; Tierney, Matthew T; Sui, Zhenhua; Sacco, Alessandra; Fowler, Velia M

2014-03-01

Duchenne muscular dystrophy (DMD) induces sarcolemmal mechanical instability and rupture, hyperactivity of intracellular calpains, and proteolytic breakdown of muscle structural proteins. Here we identify the two sarcomeric tropomodulin (Tmod) isoforms, Tmod1 and Tmod4, as novel proteolytic targets of m-calpain, with Tmod1 exhibiting ∼10-fold greater sensitivity to calpain-mediated cleavage than Tmod4 in situ. In mdx mice, increased m-calpain levels in dystrophic soleus muscle are associated with loss of Tmod1 from the thin filament pointed ends, resulting in ∼11% increase in thin filament lengths. In mdx/mTR mice, a more severe model of DMD, Tmod1 disappears from the thin filament pointed ends in both tibialis anterior (TA) and soleus muscles, whereas Tmod4 additionally disappears from soleus muscle, resulting in thin filament length increases of ∼10 and ∼12% in TA and soleus muscles, respectively. In both mdx and mdx/mTR mice, both TA and soleus muscles exhibit normal localization of α-actinin, the nebulin M1M2M3 domain, Tmod3, and cytoplasmic γ-actin, indicating that m-calpain does not cause wholesale proteolysis of other sarcomeric and actin cytoskeletal proteins in dystrophic skeletal muscle. These results implicate Tmod proteolysis and resultant thin filament length misspecification as novel mechanisms that may contribute to DMD pathology, affecting muscles in a use- and disease severity-dependent manner.

Electrically induced release of acetylcholine from denervated Schwann cells.

Science.gov (United States)

Dennis, M J; Miledi, R

1974-03-01

1. Focal electrical stimulation of Schwann cells at the end-plates of denervated frog muscles elicited slow depolarizations of up to 30 mV in the muscle fibres. This response is referred to as a Schwann-cell end-plate potential (Schwann-e.p.p.).2. Repeated stimulation sometimes evoked further Schwann-e.p.p.s, but they were never sustained for more than 30 pulses. Successive e.p.p.s varied in amplitude and time course independently of the stimulus.3. The Schwann-e.p.p.s were reversibly blocked by curare, suggesting that they result from a release of acetylcholine (ACh) by the Schwann cells.4. ACh release by electrical stimulation did not seem to occur in quantal form and was not dependent on the presence of calcium ions in the external medium; nor was it blocked by tetrodotoxin.5. Stimulation which caused release of ACh also resulted in extensive morphological disruption of the Schwann cells, as seen with both light and electron microscopy.6. It is concluded that electrical stimulation of denervated Schwann cells causes break-down of the cell membrane and releases ACh, presumably in molecular form.

"Popeye muscle" morphology in OBPI elbow flexion contracture.

Science.gov (United States)

Coroneos, Christopher J; Maizlin, Zeev V; DeMatteo, Carol; Gjertsen, Deborah; Bain, James R

2015-01-01

The pathophysiology of elbow flexion contracture (EFC) in obstetrical brachial plexus injury (OBPI) is not established. In basic science models, neonatal denervation leads to impaired muscle growth. In clinical studies, diminished growth is correlated with extent of denervation, and improved with surgical repair. In EFC, the biceps are clinically short and round vs the contralateral size, termed the "Popeye muscle". The objective of this study was to determine if the biceps morphology (muscle belly and tendon length) in arms with EFC secondary to OBPI is different vs the contralateral. This is a retrospective matched-cohort study. Patients with unilateral EFC (>20°) secondary to OBPI were identified (median = 6.6 years, range = 4.7-16.8). A blinded radiologist used computed tomography to measure length of the biceps short head muscle belly, and tendon bilaterally using standardised anatomical landmarks. Twelve patients were analyzed. The biceps muscle belly in the injured arm was shorter in all patients vs contralateral, mean difference = 3.6 cm (80%), p muscle belly and overall length, but longer tendon vs normal. This is termed the "Popeye muscle" for its irregular morphology. Findings are consistent with impaired limb growth in denervation.

Cyclosporin A preferentially attenuates skeletal slow-twitch muscle regeneration

Directory of Open Access Journals (Sweden)

Miyabara E.H.

2005-01-01

Full Text Available Calcineurin, a Ca2+/calmodulin-dependent phosphatase, is associated with muscle regeneration via NFATc1/GATA2-dependent pathways. However, it is not clear whether calcineurin preferentially affects the regeneration of slow- or fast-twitch muscles. We investigated the effect of a calcineurin inhibitor, cyclosporin A (CsA, on the morphology and fiber diameter of regenerating slow- and fast-twitch muscles. Adult Wistar rats (259.5 ± 9 g maintained under standard conditions were treated with CsA (20 mg/kg body weight, ip for 5 days, submitted to cryolesion of soleus and tibialis anterior (TA muscles on the 6th day, and then treated with CsA for an additional 21 days. The muscles were removed, weighed, frozen, and stored in liquid nitrogen. Cryolesion did not alter the body weight gain of the animals after 21 days of regeneration (P = 0.001 and CsA significantly reduced the body weight gain (15.5%; P = 0.01 during the same period. All treated TA and soleus muscles showed decreased weights (17 and 29%, respectively, P < 0.05. CsA treatment decreased the cross-sectional area of both soleus and TA muscles of cryoinjured animals (TA: 2108 ± 930 vs 792 ± 640 µm²; soleus: 2209 ± 322 vs 764 ± 439 m²; P < 0.001. Histological sections of both muscles stained with Toluidine blue revealed similar regenerative responses after cryolesion. In addition, CsA was able to minimize these responses, i.e., centralized nuclei and split fibers, more efficiently so in TA muscle. These results indicate that calcineurin preferentially plays a role in regeneration of slow-twitch muscle.

Acute Gastrocnemius-Soleus Complex Injuries in National Football League Athletes.

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Werner, Brian C; Belkin, Nicole S; Kennelly, Steve; Weiss, Leigh; Barnes, Ronnie P; Potter, Hollis G; Warren, Russell F; Rodeo, Scott A

2017-01-01

Lower extremity muscle injuries are common in professional football. Although less common than hamstring or quadriceps injuries in National Football League (NFL) athletes, calf injuries occur with relative frequency and have not previously been studied. To evaluate gastrocnemius-soleus complex muscle injuries over the past 13 years from a single NFL team to determine the incidence of such injuries, their imaging characteristics, and return to play after such injuries and any correlation between imaging findings and prolonged return to play. Case series; Level of evidence, 4. A retrospective review of all acute calf muscle injuries on a single NFL team from 2003 to 2015 was performed. Player demographics and return-to-play data were obtained from the medical records. All available magnetic resonance images (MRIs) were reviewed by a musculoskeletal radiologist for specific imaging findings that correlated with return to play. A total of 27 calf injuries in 24 NFL players were reviewed, yielding an incidence of 2.3 acute calf injuries per year on a single NFL team. Of these 27 injuries, 20 (74%) were isolated injuries to the gastrocnemius muscle, 4 (15%) were isolated injuries to the soleus muscle, and the remaining 3 injuries (11%) involved both. Defensive players were more likely to sustain injuries ( P = .043). The mean time to return to play for all 27 players was 17.4 ± 14.6 days (range, 3-62 days). MRIs were available in 14 of the 27 injuries. The average size of the fascial defect ( P = .032) and the presence of a fluid collection ( P = .031) both correlated with return to play of longer than 2 weeks. Although less common than hamstring or quadriceps muscle injuries, calf muscle injuries occur with relative frequency in the NFL, and more so in defensive players. The majority of these injuries occur in the gastrocnemius and result in significant disability, with at least 2 weeks of missed playing time on average. MRI may have an important role in the evaluation

Beneficial Effects of Renal Denervation on Pulmonary Vascular Remodeling in Experimental Pulmonary Artery Hypertension.

Science.gov (United States)

Qingyan, Zhao; Xuejun, Jiang; Yanhong, Tang; Zixuan, Dai; Xiaozhan, Wang; Xule, Wang; Zongwen, Guo; Wei, Hu; Shengbo, Yu; Congxin, Huang

2015-07-01

Activation of both the sympathetic nervous system and the renin-angiotensin-aldosterone system is closely associated with pulmonary arterial hypertension. We hypothesized that renal denervation decreases renin-angiotensin-aldosterone activity and inhibits the progression of pulmonary arterial hypertension. Twenty-two beagles were randomized into 3 groups. The dogs' pulmonary dynamics were measured before and 8 weeks after injection of 0.1mL/kg dimethylformamide (control dogs) or 2mg/kg dehydromonocrotaline (pulmonary arterial hypertension and pulmonary arterial hypertension + renal denervation dogs). Eight weeks after injection, neurohormone levels and pulmonary tissue morphology were measured. Levels of plasma angiotensin II and endothelin-1 were significantly increased after 8 weeks in the pulmonary arterial hypertension dogs and were higher in the lung tissues of these dogs than in those of the control and renal denervation dogs (mean [standard deviation] angiotensin II: 65 [9.8] vs 38 [6.7], 46 [8.1]; endothelin-1: 96 [10.3] vs 54 [6.2], 67 [9.4]; P < .01). Dehydromonocrotaline increased the mean pulmonary arterial pressure (16 [3.4] mmHg vs 33 [7.3] mmHg; P < .01), and renal denervation prevented this increase. Pulmonary smooth muscle cell proliferation was higher in the pulmonary arterial hypertension dogs than in the control and pulmonary arterial hypertension + renal denervation dogs. Renal denervation attenuates pulmonary vascular remodeling and decreases pulmonary arterial pressure in experimental pulmonary arterial hypertension. The effect of renal denervation may contribute to decreased neurohormone levels. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

How long does denervation take in poliomyelitis? Or is it a lifetime?”

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Mehmet Guney Senol

2017-01-01

Full Text Available Background and Objective: This study aims to determine the period of reinnervation in patients with poliomyelitis. This research was conducted to identify the appearance of denervation potentials in patients with poliomyelitis as indicators for reinnervation. Materials and Methods: A total of 246 male patients with poliomyelitis were assessed electrophysiologically between 1988 and 2007. The mean age was 22.8 (18–42. It has been an average of 19.9 ± 4.9 years since the beginning of complaints from the patients. Results: The patients had no complaints of newly developing muscle weakness, fatigue, muscle and joint pain, and difficulties in breathing and swallowing. Neurological examinations revealed the absence of myotomal pain and sensory loss. Upon assessment of the patients' limbs, the following findings were revealed: two patients had left upper and lower limb involvement, two patients had left upper and right lower limb involvement, 6 patients had left upper limb involvement, 12 patients had both lower limb involvement, 105 patients had left lower limb involvement, 1 patient had both upper limb involvement, 2 patients had right lower and upper limb involvement, 12 patients had right upper limb involvement, 6 patients had both lower limb involvement, 95 patients had right lower limb involvement, and 3 had all the three extremities affected. The needle electromyography revealed the presence of denervation potentials in 25.2% (62 of the patients. Conclusion: When poliovirus attacks the motor neuron, this neuron may be completely destroyed, damaged, or unaffected. Reinnervation occurs when nearby functioning motor units send out terminal axon sprouts to reinnervate the damaged muscle fibers. As a consequence of poliomyelitis, several muscle fibers become atrophic and fibrotic, but others continue to survive. This study showed that patients with a history of poliomyelitis experienced denervation with subsequent reinnervation for many years.

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.

Time course in calpain activity and autolysis in slow and fast skeletal muscle during clenbuterol treatment.

Science.gov (United States)

Douillard, Aymeric; Galbes, Olivier; Rossano, Bernadette; Vernus, Barbara; Bonnieu, Anne; Candau, Robin; Py, Guillaume

2011-02-01

Calpains are Ca2+ cysteine proteases that have been proposed to be involved in the cytoskeletal remodeling and wasting of skeletal muscle. Cumulative evidence also suggests that β2-agonists can lead to skeletal muscle hypertrophy through a mechanism probably related to calcium-dependent proteolytic enzyme. The aim of our study was to monitor calpain activity as a function of clenbuterol treatment in both slow and fast phenotype rat muscles. For this purpose, for 21 days we followed the time course of the calpain activity and of the ubiquitous calpain 1 and 2 autolysis, as well as muscle remodeling in the extensor digitorum longus (EDL) and soleus muscles of male Wistar rats treated daily with clenbuterol (4 mg·kg-1). A slow to fast fiber shift was observed in both the EDL and soleus muscles after 9 days of treatment, while hypertrophy was observed only in EDL after 9 days of treatment. Soleus muscle but not EDL muscle underwent an early apoptonecrosis phase characterized by hematoxylin and eosin staining. Total calpain activity was increased in both the EDL and soleus muscles of rats treated with clenbuterol. Moreover, calpain 1 autolysis increased significantly after 14 days in the EDL, but not in the soleus. Calpain 2 autolysis increased significantly in both muscles 6 hours after the first clenbuterol injection, indicating that clenbuterol-induced calpain 2 autolysis occurred earlier than calpain 1 autolysis. Together, these data suggest a preferential involvement of calpain 2 autolysis compared with calpain 1 autolysis in the mechanisms underlying the clenbuterol-induced skeletal muscle remodeling.

The expression of NFATc1 in adult rat skeletal muscle fibres.

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Mutungi, Gabriel

2008-03-01

Although numerous studies have recently implicated the calcineurin-nuclear factor of activated T-cells (Cn-NFAT) signalling pathway in the regulation of activity-dependent fibre type switching in adult mammalian skeletal muscles, little is known about the endogenous expression of NFAT proteins in the various fibre types present in these muscles. In this study, the immunolocalization of NFATc1 (also known as NFATc or NFAT2) in the extensor digitorum longus (EDL; a mainly fast-twitch muscle) and the soleus (a predominantly slow-twitch muscle) muscles of adult ( approximately 90-day-old) Wistar rats was investigated. The results show that NFATc1 is expressed only in oxidative fibres (i.e. type I and type IIA fibres) that stain intensely for succinate dehydrogenase activity irrespective of whether they are from the fast- or slow-twitch muscle. Thus, 99 +/- 4% (n = 7 rats) of the muscle fibres in the soleus and 42 +/- 2% (n = 7 rats) of those in the EDL expressed NFATc1. In the soleus muscle fibres, NFATc1 was localized mainly in the fibre nuclei, whereas in the EDL fibres it was localized in both the cytoplasm and the nuclei. However, no difference in its localization was observed between type I and type IIA fibres in both muscles. Western blot experiments showed that the soleus expressed more NFATc1 proteins than the EDL. From these results, we suggest that NFATc1 controls the number and distribution of both type I and type IIA fibres, as well as the oxidative capacity of adult mammalian skeletal muscles.

Charge movements and transverse tubular ultrastructure in organ cultured skeletal muscle.

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Cullen, M J; Hollingworth, S; Marshall, M W; Robson, E

1990-04-01

A study was made of charge movements and the transverse tubular systems in rat EDL and soleus muscle fibres maintained for up to five days in organ culture. In the cultured EDL muscle the maximum amount of charge moved was about one third of that in innervated muscle. Charge movements in innervated soleus fibres are small, less than 10 nC/microF, and difficult to resolve. They remain small following organ culturing. The ultrastructural study examined the concentration of junctional feet because of their proposed key role in excitation-contraction coupling. The general architecture of the triads and the spacing of the feet in both muscle types was largely unchanged by culturing. In cultured EDL muscles the small changes in feet concentration did not parallel the large fall in charge movement. The results reported here support a previous conclusion that, in mammalian muscle, there is not a simple relation between charge and feet. The stimulation of cultured soleus muscles with a fast twitch pattern of electrical activity produced no observable changes in morphology.

Neurotrophic Factor-Secreting Autologous Muscle Stem Cell Therapy for the Treatment of Laryngeal Denervation Injury

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Halum, Stacey L.; McRae, Bryan; Bijangi-Vishehsaraei, Khadijeh; Hiatt, Kelly

2012-01-01

Objectives To determine if the spontaneous reinnervation that characteristically ensues after recurrent laryngeal nerve (RLN) injury could be selectively promoted and directed to certain laryngeal muscles with the use of neurotrophic factor (NF)-secreting muscle stem cell (MSC) vectors while antagonistic reinnervation is inhibited with vincristine (VNC). Study Design Basic science investigations involving primary cell cultures, gene cloning/transfer, and animal experiments. Methods (i.) MSC survival assays were used to test multiple individual NFs in vitro. (ii.) Motoneuron outgrowth assays assessed the trophic effects of identified NF on cranial nerve X-derived (CNX) motoneurons in vitro. (iii.) Therapeutic NF was cloned into a lentiviral vector, and MSCs were tranduced to secrete NF. 60 rats underwent left RLN transection injury, and at 3 weeks received injections of either MSCs (n=24), MSCs secreting NF (n=24), or saline (n=12) into the left thyroarytenoid muscle complex (TA); half of the animals in the MSC groups simultaneously received left posterior cricoarytenoid (PCA) injections of vincristine (VNC) while half the animals received saline. Results (i.) Ciliary-derived neurotrophic factor (CNTF) had the greatest survival-promoting effect on MSCs in culture. (ii.) Addition of CNTF (50 ng/mL) to CN X motoneuron cultures resulted in enhanced neurite outgrowth and branching. (iii.) In the animal model, the injected MSCs fused with the denervated myofibers, immunohistochemistry demonstrated enhanced reinnervation based on motor endplate to nerve contact, and RT-PCR confirmed stable CNTF expression at longest follow-up (4 months) in the CNTF-secreting MSC treated groups. Conclusions MSC therapy may have a future role in selectively promoting and directing laryngeal reinnervation after RLN injury. Level of evidence: NA PMID:22965802

Renal denervation: Results of a single-center cohort study; Renale Denervation. Ergebnisse einer Single-Center Kohortenstudie

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Luetkens, J.A.; Thomas, D.; Doerner, J.; Schild, H.H.; Naehle, C.P. [Bonn Univ. (Germany). Dept. of Radiology; Wilhelm, K. [Johanniter Hospital, Bonn (Germany). Dept. of Radiology; Duesing, R. [Hypertension Center, Bonn (Germany); Woitas, R.P.; Hundt, F. [Bonn Univ. (Germany). Dept. of Internal Medicine I

2015-01-15

To investigate the effect of renal denervation on office-based and 24-h ambulatory blood pressure measurements (ABPM) in a highly selective patient population with drug-resistant hypertension. Patients with drug resistant hypertension eligible for renal denervation were included in the study population. Office blood pressure and ABPM were assessed prior to and after renal denervation. To detect procedure related renal or renal artery damage, magnetic resonance imaging (MRI) and angiography (MRA) were performed pre-interventional, one day post-interventional, and one month after renal denervation. Mean follow-up time between renal denervation and blood pressure re-assessment was 9.5 ± 3.9 months. Between August 2011 and March 2013, 17 patients prospectively underwent renal denervation. Pre-interventional mean office blood pressure and ABPM were 177.3 ± 20.3/103.8 ± 20.4 mmHg and 155.2 ± 20.5/93.7 ± 14.5 mmHg, respectively. Post-interventional, office blood pressure was significantly reduced to 144.7 ± 14.9/89.5 ± 12.1 (p < 0.05). ABPM values remained unchanged (147.9 ± 20.3/90.3 ± 15.6, p > 0.05). The number of prescribed antihypertensive drugs was unchanged after renal denervation (4.7 ± 2.0 vs. 4.2 ± 1.2, p = 0.18). No renovascular complications were detected in follow-up MRI. After renal denervation, no significant decrease in ABPM was observed. These results may indicate a limited impact of renal denervation for drug resistant hypertension.

Recruitment and rate coding organisation for soleus motor units across entire range of voluntary isometric plantar flexions.

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Oya, Tomomichi; Riek, Stephan; Cresswell, Andrew G

2009-10-01

Unlike upper limb muscles, it remains undocumented as to how motor units in the soleus muscle are organised in terms of recruitment range and discharge rates with respect to their recruitment and de-recruitment thresholds. The possible influence of neuromodulation, such as persistent inward currents (PICs) on lower limb motor unit recruitment and discharge rates has also yet to be reported. To address these issues, electromyographic (EMG) activities from the soleus muscle were recorded using selective branched-wire intramuscular electrodes during ramp-and-hold contractions with intensities up to maximal voluntary contraction (MVC). The multiple single motor unit activities were then derived using a decomposition technique. The onset-offset hysteresis of motor unit discharge, i.e. a difference between recruitment and de-recruitment thresholds, as well as PIC magnitude calculated by a paired motor unit analysis were used to examine the neuromodulatory effects on discharge behaviours, such as minimum firing rate, peak firing rate and degree of increase in firing rate. Forty-two clearly identified motor units from five subjects revealed that soleus motor units are recruited progressively from rest to contraction strengths close to 95% of MVC, with low-threshold motor units discharging action potentials slower at their recruitment and with a lower peak rate than later recruited high-threshold units. This observation is in contrast to the 'onion skin phenomenon' often reported for the upper limb muscles. Based on positive correlations of the peak discharge rates, initial rates and recruitment order of the units with the magnitude of the onset-offset hysteresis and not PIC contribution, we conclude that discharge behaviours among motor units appear to be related to a variation in an intrinsic property other than PICs.

[Parameters of fibers cell respiration and desmin content in rat soleus muscle at early stages of gravitational unloading].

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Mirzoev, T M; Biriukov, N S; Veselova, O M; Larina, I M; Shenkman, B S; Ogneva, I V

2012-01-01

The aim of the work was to study the parameters of fibers cell respiration and desmin content in Wistar rat soleus muscle after 1, 3, 7 and 14 days of gravitational unloading. Gravitational unloading was simulated by antiorthostatic hindlimb suspension. The parameters of cell respiration were determined using the polarography, and desmin content was assessed by means of Western blotting. The results showed that the intensity of cell respiration is reduced after three days of gravitational unloading, reaches a minimum level after seven days and slightly increases by the fourteenth day of hindlimb unloading, as well as the content of desmin, which, however, to the fourteenth day returns to the control level. Taking into account that mitochondrial function depends on the state of cytoskeleton the data allow us to assume that early reduction of the intensity of cell respiration under unloading could be caused by degradation of the protein desmin that determines intracellular localization of mitochondria.

Overload-induced skeletal muscle hypertrophy is not impaired in STZ-diabetic rats

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Fortes, Marco Aurélio S; Pinheiro, Carlos Hermano J; Guimarães-Ferreira, Lucas; Vitzel, Kaio F; Vasconcelos, Diogo A A; Curi, Rui

2015-01-01

The aim of this study was to evaluate the effect of overload-induced hypertrophy on extensor digitorum longus (EDL) and soleus muscles of streptozotocin-induced diabetic rats. The overload-induced hypertrophy and absolute tetanic and twitch forces increases in EDL and soleus muscles were not different between diabetic and control rats. Phospho-Akt and rpS6 contents were increased in EDL muscle after 7 days of overload and returned to the pre-overload values after 30 days. In the soleus muscle, the contents of total and phospho-Akt and total rpS6 were increased in both groups after 7 days. The contents of total Akt in controls and total rpS6 and phospho-Akt in the diabetic rats remained increased after 30 days. mRNA expression after 7 days of overload in the EDL muscle of control and diabetic animals showed an increase in MGF and follistatin and a decrease in myostatin and Axin2. The expression of FAK was increased and of MuRF-1 and atrogin-1 decreased only in the control group, whereas Ankrd2 expression was enhanced only in diabetic rats. In the soleus muscle caused similar changes in both groups: increase in FAK and MGF and decrease in Wnt7a, MuRF-1, atrogin-1, and myostatin. Differences between groups were observed only in the increased expression of follistatin in diabetic animals and decreased Ankrd2 expression in the control group. So, insulin deficiency does not impair the overload-induced hypertrophic response in soleus and EDL muscles. However, different mechanisms seem to be involved in the comparable hypertrophic responses of skeletal muscle in control and diabetic animals. PMID:26197932

Muscle pathology in lower motor neuron paraplegia and h-b FES

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Ugo Carraro

2010-03-01

Full Text Available After complete Spinal Cord Injury (SCI, causing complete disconnection between the muscle fibers and the nervous system, the denervated muscles become unexcitable with commercial electrical stimulators within several months and undergo severe atrophy and disorganization of contractile apparatus after 1-3 years. Years after the injury the surviving and regenerated myofibers are substituted with adipocytes and collagen. To counteract the progressive changes transforming muscle into an unexcitable tissue, we developed a novel therapy concept for paraplegic patients with complete lower motor neuron (LMN denervation of the lower extremities. The new stimulators for home-based functional electrical stimulation (h-b FES have been designed to reverse longstanding and severe atrophy of LMN denervated muscles by delivering high-intensity (up to 2,4 J and long-duration impulses (up to 150 ms able to elicit contractions of denervated skeletal muscle fibers in absence of nerve. Concurrent to the development of the stimulation equipment, specific clinical assessments and training strategies were developed at the Wilhelminenspital Wien, Austria. Main results of our clinical study on 20 patients, which completed a 2 years h-b FES program are: 1. significant +33% increase of muscle size and +75% of the mean diameter of muscle fibers, with striking improvements of the ultra-structural organization of contractile material; 2. recovery of the tetanic contractility with significant increase in muscle force output during electrical stimulation; 3. five subjects performed FES-assisted stand-up and stepping-in-place exercises;. 4. data from ultrastructural analyses indicating that the shorter the time span between SCI and the beginning of h-b FES, the larger were the number and the size of recovered fibers. The study demonstrates that h-b FES of permanent LMN denervated muscle is an effective home therapy that results in rescue of muscle mass, function and perfusion

Effects of hyperthyroidism and hypothyroidism on glutamine metabolism by skeletal muscle of the rat.

OpenAIRE

Parry-Billings, M; Dimitriadis, G D; Leighton, B; Bond, J; Bevan, S J; Opara, E; Newsholme, E A

1990-01-01

1. The effects of hyperthyroidism and hypothyroidism on the concentrations of glutamine and other amino acids in the muscle and plasma and on the rates of glutamine and alanine release from incubated isolated stripped soleus muscle of the rat were investigated. 2. Hyperthyroidism decreased the concentration of glutamine in soleus muscle but was without effect on that in the gastrocnemius muscle or in the plasma. Hyperthyroidism also increased markedly the rate of release of glutamine from the...

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

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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.

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

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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

IGF-I treatment improves the functional properties of fast- and slow-twitch skeletal muscles from dystrophic mice.

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Lynch, G S; Cuffe, S A; Plant, D R; Gregorevic, P

2001-04-01

Although insulin-like growth factor-I (IGF-I) has been proposed for use by patients suffering from muscle wasting conditions, few studies have investigated the functional properties of dystrophic skeletal muscle following IGF-I treatment. 129P1 ReJ-Lama2(dy) (129 ReJ dy/dy) dystrophic mice suffer from a deficiency in the structural protein, laminin, and exhibit severe muscle wasting and weakness. We tested the hypothesis that 4 weeks of IGF-I treatment ( approximately 2 mg/kg body mass, 50 g/h via mini-osmotic pump, subcutaneously) would increase the mass and force producing capacity of skeletal muscles from dystrophic mice. IGF-I treatment increased the mass of the extensor digitorum longus (EDL) and soleus muscles of dystrophic mice by 20 and 29%, respectively, compared with untreated dystrophic mice (administered saline-vehicle only). Absolute maximum force (P(o)) of the EDL and soleus muscle was increased by 40 and 32%, respectively, following IGF-I treatment. Specific P(o) (sP(o)) was increased by 23% in the EDL muscles of treated compared with untreated mice, but in the soleus muscle sP(o) was unchanged. IGF-I treatment increased the proportion of type IIB and type IIA fibres and decreased the proportion of type I fibres in the EDL muscles of dystrophic mice. In the soleus muscles of dystrophic mice, IGF-I treatment increased the proportion of type IIA fibres and decreased the proportion of type I fibres. Average fibre cross-sectional area was increased in the EDL and soleus muscles of treated compared with untreated mice. We conclude that IGF-I treatment ameliorates muscle wasting and improves the functional properties of skeletal muscles of dystrophic mice. The findings have important implications for the role of IGF-I in ameliorating muscle wasting associated with the muscular dystrophies.

Long-term high-level exercise promotes muscle reinnervation with age.

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Mosole, Simone; Carraro, Ugo; Kern, Helmut; Loefler, Stefan; Fruhmann, Hannah; Vogelauer, Michael; Burggraf, Samantha; Mayr, Winfried; Krenn, Matthias; Paternostro-Sluga, Tatjana; Hamar, Dusan; Cvecka, Jan; Sedliak, Milan; Tirpakova, Veronika; Sarabon, Nejc; Musarò, Antonio; Sandri, Marco; Protasi, Feliciano; Nori, Alessandra; Pond, Amber; Zampieri, Sandra

2014-04-01

The histologic features of aging muscle suggest that denervation contributes to atrophy, that immobility accelerates the process, and that routine exercise may protect against loss of motor units and muscle tissue. Here, we compared muscle biopsies from sedentary and physically active seniors and found that seniors with a long history of high-level recreational activity up to the time of muscle biopsy had 1) lower loss of muscle strength versus young men (32% loss in physically active vs 51% loss in sedentary seniors); 2) fewer small angulated (denervated) myofibers; 3) a higher percentage of fiber-type groups (reinnervated muscle fibers) that were almost exclusive of the slow type; and 4) sparse normal-size muscle fibers coexpressing fast and slow myosin heavy chains, which is not compatible with exercise-driven muscle-type transformation. The biopsies from the old physically active seniors varied from sparse fiber-type groupings to almost fully transformed muscle, suggesting that coexpressing fibers appear to fill gaps. Altogether, the data show that long-term physical activity promotes reinnervation of muscle fibers and suggest that decades of high-level exercise allow the body to adapt to age-related denervation by saving otherwise lost muscle fibers through selective recruitment to slow motor units. These effects on size and structure of myofibers may delay functional decline in late aging.

Skeletal muscle glucose uptake during contraction is regulated by nitric oxide and ROS independently of AMPK.

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Merry, Troy L; Steinberg, Gregory R; Lynch, Gordon S; McConell, Glenn K

2010-03-01

Reactive oxygen species (ROS) and nitric oxide (NO) have been implicated in the regulation of skeletal muscle glucose uptake during contraction, and there is evidence that they do so via interaction with AMP-activated protein kinase (AMPK). In this study, we tested the hypothesis that ROS and NO regulate skeletal muscle glucose uptake during contraction via an AMPK-independent mechanism. Isolated extensor digitorum longus (EDL) and soleus muscles from mice that expressed a muscle-specific kinase dead AMPKalpha2 isoform (AMPK-KD) and wild-type litter mates (WT) were stimulated to contract, and glucose uptake was measured in the presence or absence of the antioxidant N-acetyl-l-cysteine (NAC) or the nitric oxide synthase (NOS) inhibitor N(G)-monomethyl-l-arginine (l-NMMA). Contraction increased AMPKalpha2 activity in WT but not AMPK-KD EDL muscles. However, contraction increased glucose uptake in the EDL and soleus muscles of AMPK-KD and WT mice to a similar extent. In EDL muscles, NAC and l-NMMA prevented contraction-stimulated increases in oxidant levels (dichloroflourescein fluorescence) and NOS activity, respectively, and attenuated contraction-stimulated glucose uptake in both genotypes to a similar extent. In soleus muscles of AMPK-KD and WT mice, NAC prevented contraction-stimulated glucose uptake and l-NMMA had no effect. This is likely attributed to the relative lack of neuronal NOS in the soleus muscles compared with EDL muscles. Contraction increased AMPKalpha Thr(172) phosphorylation in EDL and soleus muscles of WT but not AMPK-KD mice, and this was not affected by NAC or l-NMMA treatment. In conclusion, ROS and NO are involved in regulating skeletal muscle glucose uptake during contraction via an AMPK-independent mechanism.

SPRINT-INTERVAL TRAINING INDUCES HEAT SHOCK PROTEIN 72 IN RAT SKELETAL MUSCLES

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Yuji Ogura

2006-06-01

Full Text Available Previous studies have demonstrated that endurance exercise training increases the level of heat shock proteins (HSPs in skeletal muscles. However, little attention has been drawn to the effects of high intensity-short duration exercise, or sprint- interval training (SIT on HSP72 level in rat skeletal muscles. This study performed to test the hypothesis that the SIT would induce the HSP72 in fast and slow skeletal muscles of rats. Young male Wistar rats (8 weeks old were randomly assigned to a control (CON or a SIT group (n = 8/group. Animals in the SIT group were trained (1 min/sprint, 6~10 sets/day and 5~6 days/week on a treadmill for 9 weeks. After the training period, HSP72 levels in the plantaris (fast and soleus (slow muscles were analyzed by Western blotting method. Enzyme activities (hexokinase, phosphofructokinase and citrate synthase and histochemical properties (muscle fiber type compositions and cross sectional area in both muscles were also determined. The SIT resulted in significantly (p < 0.05 higher levels of HSP72 in both the plantaris and soleus muscles compared to the CON group, with the plantaris producing a greater HSP72 increase than the soleus (plantaris; 550 ± 116%, soleus; 26 ± 8%, p < 0.05. Further, there were bioenergetic improvements, fast-to-slow shift of muscle fiber composition and hypertrophy in the type IIA fiber only in the plantaris muscle. These findings indicate that the SIT program increases HSP72 level of the rat hindlimb muscles, and the SIT-induced accumulation of HSP72 differs between fast and slow muscles

L-acetylcarnitine enhances functional muscle re-innervation.

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Pettorossi, V E; Brunetti, O; Carobi, C; Della Torre, G; Grassi, S

1991-01-01

The efficacy of L-acetylcarnitine and L-carnitine treatment on motor re-innervation was analyzed by evaluating different muscular parameters describing functional muscle recovery after denervation and re-innervation. The results show that L-acetylcarnitine markedly enhances functional muscle re-innervation, which on the contrary is unaffected by L-carnitine. The medial gastrocnemius muscle was denervated by cutting the nerve at the muscle entry point. After 20 days the sectioned nerve was resutured into the medial gastrocnemius muscle, and the extent of re-innervation was monitored 45 days later. L-acetylcarnitine-treated animals show significantly higher twitch and tetanic tensions of re-innervated muscle. Furthermore the results, obtained by analysing the twitch time to peak and tetanic contraction-relaxation times, suggest that L-acetylcarnitine mostly affects the functional re-innervation of slow motor units. The possible mechanisms by which L-acetylcarnitine facilitates such motor and nerve recovery are discussed.

Electrophysiological, histochemical, and hormonal adaptation of rat muscle after prolonged hindlimb suspension

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Kourtidou-Papadeli, Chrysoula; Kyparos, Antonios; Albani, Maria; Frossinis, Athanasios; Papadelis, Christos L.; Bamidis, Panagiotis; Vivas, Ana; Guiba-Tziampiri, Olympia

2004-05-01

The perspective of long-duration flights for future exploration, imply more research in the field of human adaptation. Previous studies in rat muscles hindlimb suspension (HLS), indicated muscle atrophy and a change of fibre composition from slow-to-fast twitch types. However, the contractile responses to long-term unloading is still unclear. Fifteen adult Wistar rats were studied in 45 and 70 days of muscle unweighting and soleus (SOL) muscle as well as extensor digitorum longus (EDL) were prepared for electrophysiological recordings (single, twitch, tetanic contraction and fatigue) and histochemical stainings. The loss of muscle mass observed was greater in the soleus muscle. The analysis of electrophysiological properties of both EDL and SOL showed significant main effects of group, of number of unweighting days and fatigue properties. Single contraction for soleus muscle remained unchanged but there was statistically significant difference for tetanic contraction and fatigue. Fatigue index showed a decrease for the control rats, but increase for the HLS rats. According to the histochemical findings there was a shift from oxidative to glycolytic metabolism during HLS. The data suggested that muscles atrophied, but they presented an adaptation pattern, while their endurance in fatigue was decreased.

Functional reinnervation of vocal folds after selective laryngeal adductor denervation-reinnervation surgery for spasmodic dysphonia.

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DeConde, Adam S; Long, Jennifer L; Armin, Bob B; Berke, Gerald S

2012-09-01

Selective laryngeal adductor denervation-reinnervation surgery (SLAD-R) offers a viable surgical alternative for patients with adductor spasmodic dysphonia refractory to botulinum toxin injections. SLAD-R selectively denervates the symptomatic thyroarytenoid muscle by dividing the distal adductor branch of the recurrent laryngeal nerve (RLN), and preventing reinnervation, by the proximal RLN and maintaining vocal fold bulk and tone by reinnervating the distal RLN with the ansa cervicalis. We present a patient who had previously undergone successful SLAD-R but presented 10 years postoperatively with a new regional dystonia involving his strap muscles translocated to his reinnervated larynx by his previous ansa-RLN neurorraphy. The patient's symptomatic vocal fold adduction resolved completely on division of the ansa-RLN neurorraphy confirming successful selective functional reinnervation of vocal fold adductors by the ansa cervicalis. Copyright © 2012 The Voice Foundation. Published by Mosby, Inc. All rights reserved.

Magnetic resonance imaging of skeletal muscle in patients with Duchenne muscular dystrophy; Serial axial and sagittal section studies

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Nagao, Hideo (Ehime Univ., Matsuyama (Japan). Faculty of Education); Morimoto, Takehiko; Sano, Nozomi; Takahashi, Mitsugi; Nagai, Hironao; Tawa, Ritsuko; Yoshimatsu, Makoto; Woo Young-Jong; Matsuda, Hiroshi

1991-01-01

Magnetic resonance imaging of skeletal muscles in thirteen patients with Duchenne muscular dystrophy was performed to estimate pathological changes. Serial axial and sagittal sections of the right lower extremity were recorded. In the early stage, the T{sub 1} values of gastrocnemius and soleus muscles were slightly lower than the control values, and in the late stage, the values were much lower in all muscles examined. In sagittal sections, the gastrocnemius muscle in the early stage showed a high density area at the distal region adjacent to soleus muscle, and the soleus muscle showed a high density area adjacent to the gestrocnemius muscle. In serial axial sections, high density areas of the anterior and posterior tibialis muscles appeared first at their proximal and peripheral regions. It was concluded that the sequence of appearance of pathological changes was different not only among individual muscles but also among various regions of each muscle; the high density changes appeared first at myotendon junctions. (author).

Renal denervation for treatment of drug-resistant hypertension.

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Esler, Murray

2015-02-01

At the seven-year anniversary of the first catheter-based renal denervation procedure for resistant hypertension, it is timely to reflect on the past, present, and future of the development and clinical application of this treatment. Unresolved procedural and technical questions are central: How much renal denervation is optimal? How can this level of denervation be achieved? What test for denervation can be applied in renal denervation trials? Will renal denervation show a "class effect," with the different energy forms now used for renal nerve ablation producing equivalent blood pressure lowering? When I have assessed renal denervation efficacy, using measurements of the spillover of norepinephrine from the renal sympathetic nerves to plasma, the only test validated to this point, denervation was found to be incomplete and non-uniform between patients. It is probable that the degree of denervation has commonly been suboptimal in renal denervation trials; this criticism applying with special force to the Symplicity HTN-3 trial, where the proceduralists, although expert interventional cardiologists, had no prior experience with the renal denervation technique. Recently presented results from the Symplicity HTN-3 trial confirm that renal denervation was not achieved effectively or consistently. Given this, and other difficulties in the execution of the trial relating to drug adherence, an idea mooted is that the US pivotal trial of the future may be in younger, untreated patients. Copyright © 2015 Elsevier Inc. All rights reserved.

Quantifying Ca2+ release and inactivation of Ca2+ release in fast- and slow-twitch muscles.

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Barclay, C J

2012-12-01

The aims of this study were to quantify the Ca(2+) release underlying twitch contractions of mammalian fast- and slow-twitch muscle and to comprehensively describe the transient inactivation of Ca(2+) release following a stimulus. Experiments were performed using bundles of fibres from mouse extensor digitorum longus (EDL) and soleus muscles. Ca(2+) release was quantified from the amount of ATP used to remove Ca(2+) from the myoplasm following stimulation. ATP turnover by crossbridges was blocked pharmacologically (N-benzyl-p-toluenesulphonamide for EDL, blebbistatin for soleus) and muscle heat production was used as an index of Ca(2+) pump ATP turnover. At 20°C, Ca(2+) release in response to a single stimulus was 34 and 84 μmol (kg muscle)(-1) for soleus and EDL, respectively, and increased with temperature (30°C: soleus, 61 μmol kg(-1); EDL, 168 μmol kg(-1)). Delivery of another stimulus within 100 ms of the first produced a smaller Ca(2+) release. The maximum magnitude of the decrease in Ca(2+) release was greater in EDL than soleus. Ca(2+) release recovered with an exponential time course which was faster in EDL (mean time constant at 20°C, 32.1 ms) than soleus (65.6 ms) and faster at 30°C than at 20°C. The amounts of Ca(2+) released and crossbridge cycles performed are consistent with a scheme in which Ca(2+) binding to troponin-C allowed an average of ∼1.7 crossbridge cycles in the two muscles.

Renal Denervation: a Field in Flux.

Science.gov (United States)

Laffin, Luke J; Bakris, George L

2016-07-01

SYMPLICITY HTN-3 was a pivotal moment for renal denervation as a treatment option for resistant hypertension. Prior unblinded studies were called into question given the negative results of the first sham-controlled trial of renal denervation. Reevaluation of the renal denervation procedure demonstrated that a more precise approach was needed to adequately denervate the kidney. This new approach has been implemented in two ongoing clinical trials, one on and one off medications to assess the new procedure's efficacy and safety. These and other ongoing trials will be discussed in the context of older studies in this field. We focus on novel findings published following the release of SYMPLICITY HTN-3 data in early 2014 and look to the future of renal denervation in the treatment of primary hypertension.

Pelvic denervation procedures for dysmenorrhea.

Science.gov (United States)

Ramirez, Christina; Donnellan, Nicole

2017-08-01

Chronic pelvic pain and dysmenorrhea are common conditions affecting reproductive-age women. Surgical pelvic denervation procedures may be a treatment option for women with midline dysmenorrhea, in which medical management is declined by the patient, ineffective at managing symptoms, or medically contraindicated. This review describes the surgical techniques and complications associated with pelvic denervation procedures as well as the current evidence for these procedures in women with primary dysmenorrhea and dysmenorrhea secondary to endometriosis. Presacral neurectomy is the preferred pelvic denervation procedure in patients with primary dysmenorrhea and midline chronic pelvic pain associated with endometriosis. In patients with endometriosis presacral neurectomy is a useful adjunct to excision or ablation of all endometrial lesions to improve postoperative pain relief. There is no additional patient benefit of performing combined presacral neurectomy and uterine nerve ablation procedures. Pelvic denervation procedures can be performed safely and quickly with a low risk of complication if the surgeon is knowledgeable and skilled in operating in the presacral space. Patients should be adequately counseled on expected success rates and potential complications associated with pelvic denervation procedures.

The arrangement of muscle fibers and tendons in two muscles used for growth studies.

OpenAIRE

Stickland, N C

1983-01-01

The arrangement of muscle fibres and tendons was examined in the soleus muscle of rats from 6 to 175 days post partum. The muscle was seen to change from a simple structure, with mean fibre length of approximately 90% of complete muscle length, to a unipennate structure, with mean fibre length of only about 60% of muscle length. The dog pectineus muscle was also investigated and found to have a bipennate structure throughout postnatal growth. The arrangement of muscle fibres in both these mus...

Muscle plasticity related to changes in tubulin and αB-crystallin levels induced by eccentric contraction in rat skeletal muscles.

Science.gov (United States)

Jee, H; Ochi, E; Sakurai, T; Lim, J-Y; Nakazato, K; Hatta, H

2016-09-01

We used the model of eccentric contraction of the hindlimb muscle by Ochi et al. to examine the role of eccentric contraction in muscle plasticity. This model aims to focus on stimulated skeletal muscle responses by measuring tissue weights and tracing the quantities of αB-crystallin and tubulin. The medial gastrocnemius muscle (GCM) responded to electrically induced eccentric contraction (EIEC) with significant increases in tissue weight (p muscle weight after EIEC. EIEC in the GCM caused contractile-induced sustenance of the traced proteins, but the soleus muscle exhibited a remarkable decrease in α-tubulin and a 19% decrease in αB-crystallin. EIEC caused fast-to-slow myosin heavy chain (MHC) isoform type-oriented shift within both the GCM and soleus muscle. These results have shown that different MHC isoform type-expressing slow and fast muscles commonly undergo fast-to-slow type MHC isoform transformation. This suggests that different levels of EIEC affected each of the slow and fast muscles to induce different quantitative changes in the expression of αB-crystallin and α-tubulin.

Reinnervation following catheter-based radio-frequency renal denervation.

Science.gov (United States)

Booth, Lindsea C; Nishi, Erika E; Yao, Song T; Ramchandra, Rohit; Lambert, Gavin W; Schlaich, Markus P; May, Clive N

2015-04-20

What is the topic of this review? Does catheter-based renal denervation effectively denervate the afferent and efferent renal nerves and does reinnervation occur? What advances does it highlight? Following catheter-based renal denervation, the afferent and efferent responses to electrical stimulation were abolished, renal sympathetic nerve activity was absent, and levels of renal noradrenaline and immunohistochemistry for tyrosine hydroxylase and calcitonin gene-related peptide were significantly reduced. By 11 months after renal denervation, both the functional responses and anatomical markers of afferent and efferent renal nerves had returned to normal, indicating reinnervation. Renal denervation reduces blood pressure in animals with experimental hypertension and, recently, catheter-based renal denervation was shown to cause a prolonged decrease in blood pressure in patients with resistant hypertension. The randomized, sham-controlled Symplicity HTN-3 trial failed to meet its primary efficacy end-point, but there is evidence that renal denervation was incomplete in many patients. Currently, there is little information regarding the effectiveness of catheter-based renal denervation and the extent of reinnervation. We assessed the effectiveness of renal nerve denervation with the Symplicity Flex catheter and the functional and anatomical reinnervation at 5.5 and 11 months postdenervation. In anaesthetized, non-denervated sheep, there was a high level of renal sympathetic nerve activity, and electrical stimulation of the renal nerve increased blood pressure and reduced heart rate (afferent response) and caused renal vasoconstriction and reduced renal blood flow (efferent response). Immediately after renal denervation, renal sympathetic nerve activity and the responses to electrical stimulation were absent, indicating effective denervation. By 11 months after denervation, renal sympathetic nerve activity was present and the responses to electrical stimulation

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.

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.

Baseline muscle mass is a poor predictor of functional overload-induced gain in the mouse model

Directory of Open Access Journals (Sweden)

Audrius Kilikevicius

2016-11-01

Full Text Available Genetic background contributes substantially to individual variability in muscle mass. Muscle hypertrophy in response to resistance training can also vary extensively. However, it is less clear if muscle mass at baseline is predictive of the hypertrophic response.The aim of this study was to examine the effect of genetic background on variability in muscle mass at baseline and in the adaptive response of the mouse fast- and slow-twitch muscles to overload. Males of eight laboratory mouse strains: C57BL/6J (B6, n=17, BALB/cByJ (n=7, DBA/2J (D2, n=12, B6.A-(rs3676616-D10Utsw1/Kjn (B6.A, n=9, C57BL/6J-Chr10A/J/NaJ (B6.A10, n=8, BEH+/+ (n=11, BEH (n=12 and DUHi (n=12, were studied. Compensatory growth of soleus and plantaris muscles was triggered by a 4-week overload induced by synergist unilateral ablation. Muscle weight in the control leg (baseline varied from 5.2±07 mg soleus and 11.4±1.3 mg plantaris in D2 mice to 18.0±1.7 mg soleus in DUHi and 43.7±2.6 mg plantaris in BEH (p<0.001 for both muscles. In addition, soleus in the B6.A10 strain was ~40% larger (p<0.001 compared to the B6. Functional overload increased muscle weight, however, the extent of gain was strain-dependent for both soleus (p<0.01 and plantaris (p<0.02 even after accounting for the baseline differences. For the soleus muscle, the BEH strain emerged as the least responsive, with a 1.3-fold increase, compared to a 1.7-fold gain in the most responsive D2 strain, and there was no difference in the gain between the B6.A10 and B6 strains. The BEH strain appeared the least responsive in the gain of plantaris as well, 1.3-fold, compared to ~1.5-fold gain in the remaining strains. We conclude that variation in muscle mass at baseline is not a reliable predictor of that in the overload-induced gain. This suggests that a different set of genes influence variability in muscle mass acquired in the process of normal development, growth and maintenance, and in the process of adaptive

Estrogen regulates estrogen receptors and antioxidant gene expression in mouse skeletal muscle.

Directory of Open Access Journals (Sweden)

Kristen A Baltgalvis

Full Text Available BACKGROUND: Estrogens are associated with the loss of skeletal muscle strength in women with age. Ovarian hormone removal by ovariectomy in mice leads to a loss of muscle strength, which is reversed with 17beta-estradiol replacement. Aging is also associated with an increase in antioxidant stress, and estrogens can improve antioxidant status via their interaction with estrogen receptors (ER to regulate antioxidant gene expression. The purpose of this study was to determine if ER and antioxidant gene expression in skeletal muscle are responsive to changes in circulating estradiol, and if ERs regulate antioxidant gene expression in this tissue. METHODOLOGY/PRINCIPAL FINDINGS: Adult C57BL/6 mice underwent ovariectomies or sham surgeries to remove circulating estrogens. These mice were implanted with placebo or 17beta-estradiol pellets acutely or chronically. A separate experiment examined mice that received weekly injections of Faslodex to chronically block ERs. Skeletal muscles were analyzed for expression of ER genes and proteins and antioxidant genes. ERalpha was the most abundant, followed by Gper and ERbeta in both soleus and EDL muscles. The loss of estrogens through ovariectomy induced ERalpha gene and protein expression in the soleus, EDL, and TA muscles at both the acute and chronic time points. Gpx3 mRNA was also induced both acutely and chronically in all 3 muscles in mice receiving 17beta-estradiol. When ERs were blocked using Faslodex, Gpx3 mRNA was downregulated in the soleus muscle, but not the EDL and TA muscles. CONCLUSIONS/SIGNIFICANCE: These data suggest that Gpx3 and ERalpha gene expression are sensitive to circulating estrogens in skeletal muscle. ERs may regulate Gpx3 gene expression in the soleus muscle, but skeletal muscle regulation of Gpx3 via ERs is dependent upon muscle type. Further work is needed to determine the indirect effects of estrogen and ERalpha on Gpx3 expression in skeletal muscle, and their importance in the

Effect of anabolic steroids on skeletal muscle mass during hindlimb suspension

Science.gov (United States)

Tsika, R. W.; Herrick, R. E.; Baldwin, K. M.

1987-01-01

The effect of treatment with an anabolic steroid (nandrolone decanoate) on the muscle mass of plantaris and soleus of a rats in hindlimb suspension, and on the isomyosin expression in these muscles, was investigated in young female rats divided into four groups: normal control (NC), normal steroid (NS), normal suspension (N-sus), and suspension steroid (sus-S). Steroid treatment of suspended animals (sus-S vs N-sus) was found to partially spare body weight and muscle weight, as well as myofibril content of plantaris (but not soleus), but did not modify the isomyosin pattern induced by suspension. In normal rats (NS vs NC), steroid treatment did enhance body weight and plantaris muscle weight; the treatment did not alter isomyosin expression in either muscle type.

Is Tadpole Pupil in an Adolescent Girl Caused by Denervation Hypersensitivity?

Science.gov (United States)

Hansen, Jonas Kjeldbjerg; Møller, Hans Ulrik

2017-06-01

Tadpole pupil is a rarely encountered phenomenon caused by episodic, segmental iris dilator muscle spasm of short duration (2-15 minutes), occurring in clusters without a known precipitating factor. It has most commonly been described in women aged 28 to 48 years. A few hypotheses on pathogenesis have been discussed but none has been proved. Here, we present an adolescent girl with bilateral tadpole pupil that appeared during physical exercise. This is the first pediatric case of tadpole pupil, not caused by preceding surgery, to be published. Based on (1) this case in which tadpole pupil developed when the norepinephrine level rose during exercise, (2) the high ratio of patients with tadpole pupil who concurrently have or later develop Horner syndrome, in which denervation hypersensitivity is well described, (3) a previous report of a patient with both tadpole pupil and Horner syndrome who had denervation hypersensitivity on pharmacological testing, (4) a 29-year-old man with unilateral tadpole pupil induced by exercise, and (5) a 19-year-old man with bilateral tadpole pupil and possible autonomic neuropathy, we suggest denervation hypersensitivity as a probable pathogenic mechanism causing tadpole pupil. In addition, a suggestion for investigations to be performed in future pediatric cases is provided. Georg Thieme Verlag KG Stuttgart · New York.

Real Time RT-PCR with a Newly Designed Set of Promers Confirmed the Presence of 2b and 2x/d Myosim Heavy Chain mRNAs in the Rat Slow Soleus Muscle

Czech Academy of Sciences Publication Activity Database

Žurmanová, Jitka; Půta, F.; Stopková, R.; Soukup, Tomáš

2008-01-01

Roč. 57, č. 6 (2008), s. 973-978 ISSN 0862-8408 R&D Projects: GA MŠk(CZ) LC554; GA ČR(CZ) GA305/06/1115; GA ČR(CZ) GA304/08/0256 Grant - others:EC(XE) LSH-CT-2004-511978 Institutional research plan: CEZ:AV0Z50110509 Keywords : rat slow soleus muscle * myosin heavy chain isoforms * real time RT-PCR Subject RIV: ED - Physiology Impact factor: 1.653, year: 2008

MR imaging of accessory muscles of the ankle

International Nuclear Information System (INIS)

Mondello, Eduardo; Nazar, Miguel E.; Martin, Eduardo

2001-01-01

Purpose: The purpose of this work is to describe the normal anatomy and the characteristics in MRI of the accessory muscles of the posterior ankle: the accessory soleus, accessory flexor digitorum longus, peroneus quartus, tibiocalcaneus internus and peroneocalcaneus internus. Material and methods: There were evaluated 280 symptomatic patients between 18 and 40 years old (85 % males). MR was performed in High Field Magnetic Resonance Units (1.5 T y 1.0 T) and multiplanar sequences. Results: We found 2 peroneus quartus (0.7%), 2 accessory soleus muscles (0.7%), 3 accessory flexor digitorum longus (1.07%) and 1 peroneocalcaneus internus (0.35%). Conclusion: The knowledge of the accessory muscles of the posterior ankle allow to explain different painful pathologies with instability or tendinous tears, which are difficult to diagnose if the muscle are not adequately recognized. (author)

Lower extremity muscle functions during full squats.

Science.gov (United States)

Robertson, D G E; Wilson, Jean-Marie J; St Pierre, Taunya A

2008-11-01

The purpose of this research was to determine the functions of the gluteus maximus, biceps femoris, semitendinosus, rectus femoris, vastus lateralis, soleus, gastrocnemius, and tibialis anterior muscles about their associated joints during full (deep-knee) squats. Muscle function was determined from joint kinematics, inverse dynamics, electromyography, and muscle length changes. The subjects were six experienced, male weight lifters. Analyses revealed that the prime movers during ascent were the monoarticular gluteus maximus and vasti muscles (as exemplified by vastus lateralis) and to a lesser extent the soleus muscles. The biarticular muscles functioned mainly as stabilizers of the ankle, knee, and hip joints by working eccentrically to control descent or transferring energy among the segments during scent. During the ascent phase, the hip extensor moments of force produced the largest powers followed by the ankle plantar flexors and then the knee extensors. The hip and knee extensors provided the initial bursts of power during ascent with the ankle extensors and especially a second burst from the hip extensors adding power during the latter half of the ascent.

Renal denervation: unde venis et quo vadis?

Science.gov (United States)

Nähle, C P; Düsing, R; Schild, H

2015-04-01

Renal denervation is a minimally invasive, catheter-based option for the treatment of refractory hypertension. Indications and contraindications for renal denervation have been defined in an interdisciplinary manner. The efficacy and safety of the procedure were evaluated. Currently, indication for renal denervation is limited to patients with primary hypertension and a systolic blood pressure of ≥ 160 mm Hg (or ≥ 150 mm Hg in diabetes type 2) despite optimal medical therapy with ≥ 3 different antihypertensive drugs. In this specific patient population, an average blood pressure reduction of 32/14 mmHg was observed in non-randomized/-controlled trials after renal denervation. These results were not confirmed in the first randomized controlled trial with a non-significantly superior blood pressure reduction of 14.1 ± 23.9 mm Hg compared to controls (-11.74 ± 25.94 mm Hg, difference -2.39 mm Hg p = 0.26 for superiority with a margin of 5 mm Hg) who underwent a sham procedure. The efficacy and long-term effects of renal denervation need to be re-evaluated in light of the HTN3 study results. To date, renal denervation should not be performed outside of clinical trials. Future trials should also assess if renal denervation can be performed with sufficient safety and efficacy in patients with hypertension-associated diseases. The use of renal denervation as an alternative therapy (e. g. in patients with drug intolerance) can currently not be advocated. The indication for renal denervation should be assessed in an interdisciplinary fashion and according to current guidelines with a special focus on ruling out secondary causes for arterial hypertension. 5 - 10 % of patients with hypertension suffer from refractory hypertension, but only about 1 % of patients meet the criteria for a renal denervation. Renal denervation leads to a significant decrease in office blood pressure; however, the impact on 24-hour blood pressure

Response of slow and fast muscle to hypothyroidism: maximal shortening velocity and myosin isoforms

Science.gov (United States)

Caiozzo, V. J.; Herrick, R. E.; Baldwin, K. M.

1992-01-01

This study examined both the shortening velocity and myosin isoform distribution of slow- (soleus) and fast-twitch (plantaris) skeletal muscles under hypothyroid conditions. Adult female Sprague-Dawley rats were randomly assigned to one of two groups: control (n = 7) or hypothyroid (n = 7). In both muscles, the relative contents of native slow myosin (SM) and type I myosin heavy chain (MHC) increased in response to the hypothyroid treatment. The effects were such that the hypothyroid soleus muscle expressed only the native SM and type I MHC isoforms while repressing native intermediate myosin and type IIA MHC. In the plantaris, the relative content of native SM and type I MHC isoforms increased from 5 to 13% and from 4 to 10% of the total myosin pool, respectively. Maximal shortening velocity of the soleus and plantaris as measured by the slack test decreased by 32 and 19%, respectively, in response to hypothyroidism. In contrast, maximal shortening velocity as estimated by force-velocity data decreased only in the soleus (-19%). No significant change was observed for the plantaris.

Chemical renal denervation in the rat.

Science.gov (United States)

Consigny, Paul M; Davalian, Dariush; Donn, Rosy; Hu, Jie; Rieser, Matthew; Stolarik, Deanne

2014-02-01

The recent success of renal denervation in lowering blood pressure in drug-resistant hypertensive patients has stimulated interest in developing novel approaches to renal denervation including local drug/chemical delivery. The purpose of this study was to develop a rat model in which depletion of renal norepinephrine (NE) could be used to determine the efficacy of renal denervation after the delivery of a chemical to the periadventitial space of the renal artery. Renal denervation was performed on a single renal artery of 90 rats (n = 6 rats/group). The first study determined the time course of renal denervation after surgical stripping of a renal artery plus the topical application of phenol in alcohol. The second study determined the efficacy of periadventitial delivery of hypertonic saline, guanethidine, and salicylic acid. The final study determined the dose-response relationship for paclitaxel. In all studies, renal NE content was determined by liquid chromatography-mass spectrometry. Renal NE was depleted 3 and 7 days after surgical denervation. Renal NE was also depleted by periadventitial delivery of all agents tested (hypertonic saline, salicylic acid, guanethidine, and paclitaxel). A dose response was observed after the application of 150 μL of 10(-5) M through 10(-2) M paclitaxel. We developed a rat model in which depletion of renal NE was used to determine the efficacy of renal denervation after perivascular renal artery drug/chemical delivery. We validated this model by demonstrating the efficacy of the neurotoxic agents hypertonic saline, salicylic acid, and guanethidine and increasing doses of paclitaxel.

Lactate and force production in skeletal muscle

DEFF Research Database (Denmark)

Kristensen, Michael; Albertsen, Janni; Rentsch, Maria

2005-01-01

Lactic acid accumulation is generally believed to be involved in muscle fatigue. However, one study reported that in rat soleus muscle (in vitro), with force depressed by high external K+ concentrations a subsequent incubation with lactic acid restores force and thereby protects against fatigue...

Matching of sarcoplasmic reticulum and contractile properties in rat fast- and slow-twitch muscle fibres.

Science.gov (United States)

Trinh, Huong H; Lamb, Graham D

2006-07-01

1. The twitch characteristics (fast-twitch or slow-twitch) of skeletal muscle fibres are determined not only by the contractile apparatus properties of the fibre, but also by the time-course of Ca2+ release and re-uptake by the sarcoplasmic reticulum (SR). The present study examined, in individual fibres from non-transforming muscle of the rat, whether particular SR properties are matched to the contractile apparatus properties of the fibre, in particular in the case of fibres with fast-twitch contractile apparatus located in a slow-twitch muscle, namely the soleus. 2. Force was recorded in single, mechanically skinned fibres from extensor digitorum longus (EDL), gastrocnemius, peroneus longus and soleus muscles. Using repeated cycles in which the SR was emptied of all releasable Ca2+ and then reloaded, it was possible to determine the relative amount of Ca2+ present in the SR endogenously, the maximum SR capacity and the rate of Ca2+ loading. The sensitivity of the contractile apparatus to Ca2+ and Sr2+ was used to classify the fibres as fast-twitch (FT), slow-twitch (ST) or mixed (fibres examined) and thereby identify the likely troponin C and myosin heavy chain types present. 3. There was no significant difference in SR properties between the groups of FT fibres obtained from the four different muscles, including soleus. Despite some overlap in the SR properties of individual fibres between the FT and ST groups, the properties of the FT fibres in all four muscles studied were significantly different from those of the ST and mixed fibres. 4. In general, in FT fibres the SR had a larger capacity and the endogenous Ca2+ content was a relatively lower percentage of maximum compared with ST fibres. Importantly, in terms of their SR properties, FT fibres from soleus muscle more closely resembled FT fibres from other muscles than they did ST fibres from soleus muscle.

Does complete renal denervation translate into superior clinical outcomes? Lessons learned from denervation of accessory renal arteries

OpenAIRE

Mendelsohn, Farrell O.

2014-01-01

Pre-clinical studies of renal denervation would suggest that the extent of renal nerve injury correlates with outcomes. The “completeness” of renal nerve injury following renal denervation correlates with treatment-based variables such as the depth of ablation, the number of ablations along the length of the artery, and the number of renal arteries successfully ablated. Renal denervation techniques targeting only main renal arteries may lead to suboptimal results in patients with accessory re...

Eligibility for renal denervation

DEFF Research Database (Denmark)

Persu, Alexandre; Jin, Yu; Baelen, Marie

2014-01-01

-resistant hypertension (ENCOReD). The analysis included 731 patients. Age averaged 61.6 years, office blood pressure at screening was 177/96 mm Hg, and the number of blood pressure-lowering drugs taken was 4.1. Specialists referred 75.6% of patients. The proportion of patients eligible for renal denervation according...... undetected secondary causes of hypertension (11.1%). In conclusion, after careful screening and treatment adjustment at hypertension expert centers, only ≈40% of patients referred for renal denervation, mostly by specialists, were eligible for the procedure. The most frequent cause of ineligibility...... (approximately half of cases) was blood pressure normalization after treatment adjustment by a hypertension specialist. Our findings highlight that hypertension centers with a record in clinical experience and research should remain the gatekeepers before renal denervation is considered....

Chemical Renal Denervation in the Rat

Energy Technology Data Exchange (ETDEWEB)

Consigny, Paul M., E-mail: paul.consigny@av.abbott.com; Davalian, Dariush, E-mail: dariush.davalian@av.abbott.com [Abbott Vascular, Innovation Incubator (United States); Donn, Rosy, E-mail: rosy.donn@av.abbott.com; Hu, Jie, E-mail: jie.hu@av.abbott.com [Abbott Vascular, Bioanalytical and Material Characterization (United States); Rieser, Matthew, E-mail: matthew.j.rieser@abbvie.com; Stolarik, DeAnne, E-mail: deanne.f.stolarik@abbvie.com [Abbvie, Analytical Pharmacology (United States)

2013-12-03

Introduction: The recent success of renal denervation in lowering blood pressure in drug-resistant hypertensive patients has stimulated interest in developing novel approaches to renal denervation including local drug/chemical delivery. The purpose of this study was to develop a rat model in which depletion of renal norepinephrine (NE) could be used to determine the efficacy of renal denervation after the delivery of a chemical to the periadventitial space of the renal artery. Methods: Renal denervation was performed on a single renal artery of 90 rats (n = 6 rats/group). The first study determined the time course of renal denervation after surgical stripping of a renal artery plus the topical application of phenol in alcohol. The second study determined the efficacy of periadventitial delivery of hypertonic saline, guanethidine, and salicylic acid. The final study determined the dose–response relationship for paclitaxel. In all studies, renal NE content was determined by liquid chromatography–mass spectrometry. Results: Renal NE was depleted 3 and 7 days after surgical denervation. Renal NE was also depleted by periadventitial delivery of all agents tested (hypertonic saline, salicylic acid, guanethidine, and paclitaxel). A dose response was observed after the application of 150 μL of 10{sup −5} M through 10{sup −2} M paclitaxel. Conclusion: We developed a rat model in which depletion of renal NE was used to determine the efficacy of renal denervation after perivascular renal artery drug/chemical delivery. We validated this model by demonstrating the efficacy of the neurotoxic agents hypertonic saline, salicylic acid, and guanethidine and increasing doses of paclitaxel.

Chemical Renal Denervation in the Rat

International Nuclear Information System (INIS)

Consigny, Paul M.; Davalian, Dariush; Donn, Rosy; Hu, Jie; Rieser, Matthew; Stolarik, DeAnne

2014-01-01

Introduction: The recent success of renal denervation in lowering blood pressure in drug-resistant hypertensive patients has stimulated interest in developing novel approaches to renal denervation including local drug/chemical delivery. The purpose of this study was to develop a rat model in which depletion of renal norepinephrine (NE) could be used to determine the efficacy of renal denervation after the delivery of a chemical to the periadventitial space of the renal artery. Methods: Renal denervation was performed on a single renal artery of 90 rats (n = 6 rats/group). The first study determined the time course of renal denervation after surgical stripping of a renal artery plus the topical application of phenol in alcohol. The second study determined the efficacy of periadventitial delivery of hypertonic saline, guanethidine, and salicylic acid. The final study determined the dose–response relationship for paclitaxel. In all studies, renal NE content was determined by liquid chromatography–mass spectrometry. Results: Renal NE was depleted 3 and 7 days after surgical denervation. Renal NE was also depleted by periadventitial delivery of all agents tested (hypertonic saline, salicylic acid, guanethidine, and paclitaxel). A dose response was observed after the application of 150 μL of 10 −5  M through 10 −2  M paclitaxel. Conclusion: We developed a rat model in which depletion of renal NE was used to determine the efficacy of renal denervation after perivascular renal artery drug/chemical delivery. We validated this model by demonstrating the efficacy of the neurotoxic agents hypertonic saline, salicylic acid, and guanethidine and increasing doses of paclitaxel

Long-Term Quercetin Dietary Enrichment Partially Protects Dystrophic Skeletal Muscle.

Directory of Open Access Journals (Sweden)

Hannah R Spaulding

Full Text Available Duchenne muscular dystrophy (DMD results from a genetic lesion in the dystrophin gene and leads to progressive muscle damage. PGC-1α pathway activation improves muscle function and decreases histopathological injury. We hypothesized that mild disease found in the limb muscles of mdx mice may be responsive to quercetin-mediated protection of dystrophic muscle via PGC-1α pathway activation. To test this hypothesis muscle function was measured in the soleus and EDL from 14 month old C57, mdx, and mdx mice treated with quercetin (mdxQ; 0.2% dietary enrichment for 12 months. Quercetin reversed 50% of disease-related losses in specific tension and partially preserved fatigue resistance in the soleus. Specific tension and resistance to contraction-induced injury in the EDL were not protected by quercetin. Given some functional gain in the soleus it was probed with histological and biochemical approaches, however, in dystrophic muscle histopathological outcomes were not improved by quercetin and suppressed PGC-1α pathway activation was not increased. Similar to results in the diaphragm from these mice, these data suggest that the benefits conferred to dystrophic muscle following 12 months of quercetin enrichment were underwhelming. Spontaneous activity at the end of the treatment period was greater in mdxQ compared to mdx indicating that quercetin fed mice were more active in addition to engaging in more vigorous activity. Hence, modest preservation of muscle function (specific tension and elevated spontaneous physical activity largely in the absence of tissue damage in mdxQ suggests dietary quercetin may mediate protection.

Differentiation of the intracellular structure of slow- versus fast-twitch muscle fibers through evaluation of the dielectric properties of tissue

Science.gov (United States)

Sanchez, B.; Li, J.; Bragos, R.; Rutkove, S. B.

2014-05-01

Slow-twitch (type 1) skeletal muscle fibers have markedly greater mitochondrial content than fast-twitch (type 2) fibers. Accordingly, we sought to determine whether the dielectric properties of these two fiber types differed, consistent with their distinct intracellular morphologies. The longitudinal and transverse dielectric spectrum of the ex vivo rat soleus (a predominantly type 1 muscle) and the superficial layers of rat gastrocnemius (predominantly type 2) (n = 15) were measured in the 1 kHz-10 MHz frequency range and modeled to a resistivity Cole-Cole function. Major differences were especially apparent in the dielectric spectrum in the 1 to 10 MHz range. Specifically, the gastrocnemius demonstrated a well-defined, higher center frequency than the soleus muscle, whereas the soleus muscle showed a greater difference in the modeled zero and infinite resistivities than the gastrocnemius. These findings are consistent with the fact that soleus tissue has larger and more numerous mitochondria than gastrocnemius. Evaluation of tissue at high frequency could provide a novel approach for assessing intracellular structure in health and disease.

Differentiation of the intracellular structure of slow- versus fast-twitch muscle fibers through evaluation of the dielectric properties of tissue

International Nuclear Information System (INIS)

Sanchez, B; Li, J; Rutkove, S B; Bragos, R

2014-01-01

Slow-twitch (type 1) skeletal muscle fibers have markedly greater mitochondrial content than fast-twitch (type 2) fibers. Accordingly, we sought to determine whether the dielectric properties of these two fiber types differed, consistent with their distinct intracellular morphologies. The longitudinal and transverse dielectric spectrum of the ex vivo rat soleus (a predominantly type 1 muscle) and the superficial layers of rat gastrocnemius (predominantly type 2) (n = 15) were measured in the 1 kHz–10 MHz frequency range and modeled to a resistivity Cole–Cole function. Major differences were especially apparent in the dielectric spectrum in the 1 to 10 MHz range. Specifically, the gastrocnemius demonstrated a well-defined, higher center frequency than the soleus muscle, whereas the soleus muscle showed a greater difference in the modeled zero and infinite resistivities than the gastrocnemius. These findings are consistent with the fact that soleus tissue has larger and more numerous mitochondria than gastrocnemius. Evaluation of tissue at high frequency could provide a novel approach for assessing intracellular structure in health and disease. (paper)

Muscle and joint sequelae in brachial plexus injury

NARCIS (Netherlands)

Duijnisveld, B.J.

2016-01-01

A brachial plexus injury is caused by traction on the brachial plexus during delivery or due to a high-energy road traffic accident in young adults. Muscle denervation and subsequent muscle degeneration results in functional limitations of the shoulder, elbow, wrist and hand including contractures

Metabolic characteristics of skeletal muscle from lean and obese Zucker rats

International Nuclear Information System (INIS)

Campion, D.R.; Shapira, J.F.; Allen, C.E.; Hausman, G.J.; Martin, R.J.

1987-01-01

The purpose of this study was to determine if the metabolic response to obesity and to pair feeding of obese Zucker rats to lean Zucker rats was similar across skeletal muscles. Oxidation of glucose, palmitate and isoleucine was studied in muscle strips in vitro using appropriate 14- carbon substrates as tracers. The plantaris muscle was subjected to histochemical analyses using an alkaline actomyosin ATPase, NADH-tetrazolium reductase and an oil red 0 stain. Soleus muscles from both ad libitum and pair fed obese rats oxidized less glucose to CO 2 , but released similar amounts of lactate when compared to the soleus muscles of lean rats. Oxidation of glucose was similar in the extensor digitorum longus (EDL) muscle of ad libitum fed obese rats, but lower when pair fed to the intake of lean rats. No differences were apparent in palmitate oxidation to CO 2 or in incorporation into lipid, except in the EDL muscle of pair-fed obese rats which exhibited a higher rate for palmitate metabolism when compared with lean rats. Isoleucine oxidation to CO 2 was higher in the EDL and plantaris muscles, but similar in the soleus muscle of ad libitum-fed obese rats when compared with lean rats. The magnitude of the difference in isoleucine oxidation was similar when the obese rats were pair fed. No differences in the percentage of plantaris muscle fibers sensitive to alkaline ATPase staining were observed. The plantaris muscle of obese rats, contained a higher proportion of oxidative fibers. These results indicate the great risk in generalizing about metabolic activity of the whole skeletal muscle mass based on observations made on one, or even two, distinct muscles in this animal model. Also, pair feeding of obese to lean Zucker rats did not result in uniform change sin metabolism between muscles of the obese rats

RENAL DENERVATION IN RESISTANT ARTERIAL HYPERTENSION

OpenAIRE

V. A. Sulimov; A. V. Rodionov; A. A. Svetankova; I. E. Deneka

2015-01-01

A new method of non-drug treatment of resistant hypertension – renal denervation is considered. General information about resistant hypertension, method of renal denervation, the results of clinical studies on efficacy and safety, as well as own clinical case are presented.

Twenty-Four-Hour Blood Pressure Monitoring to Predict and Assess Impact of Renal Denervation: The DENERHTN Study (Renal Denervation for Hypertension).

Science.gov (United States)

Gosse, Philippe; Cremer, Antoine; Pereira, Helena; Bobrie, Guillaume; Chatellier, Gilles; Chamontin, Bernard; Courand, Pierre-Yves; Delsart, Pascal; Denolle, Thierry; Dourmap, Caroline; Ferrari, Emile; Girerd, Xavier; Michel Halimi, Jean; Herpin, Daniel; Lantelme, Pierre; Monge, Matthieu; Mounier-Vehier, Claire; Mourad, Jean-Jacques; Ormezzano, Olivier; Ribstein, Jean; Rossignol, Patrick; Sapoval, Marc; Vaïsse, Bernard; Zannad, Faiez; Azizi, Michel

2017-03-01

The DENERHTN trial (Renal Denervation for Hypertension) confirmed the blood pressure (BP) lowering efficacy of renal denervation added to a standardized stepped-care antihypertensive treatment for resistant hypertension at 6 months. We report here the effect of denervation on 24-hour BP and its variability and look for parameters that predicted the BP response. Patients with resistant hypertension were randomly assigned to denervation plus stepped-care treatment or treatment alone (control). Average and standard deviation of 24-hour, daytime, and nighttime BP and the smoothness index were calculated on recordings performed at randomization and 6 months. Responders were defined as a 6-month 24-hour systolic BP reduction ≥20 mm Hg. Analyses were performed on the per-protocol population. The significantly greater BP reduction in the denervation group was associated with a higher smoothness index ( P =0.02). Variability of 24-hour, daytime, and nighttime BP did not change significantly from baseline to 6 months in both groups. The number of responders was greater in the denervation (20/44, 44.5%) than in the control group (11/53, 20.8%; P =0.01). In the discriminant analysis, baseline average nighttime systolic BP and standard deviation were significant predictors of the systolic BP response in the denervation group only, allowing adequate responder classification of 70% of the patients. Our results show that denervation lowers ambulatory BP homogeneously over 24 hours in patients with resistant hypertension and suggest that nighttime systolic BP and variability are predictors of the BP response to denervation. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01570777. © 2017 American Heart Association, Inc.

Muscle-tendon mechanics explain unexpected effects of exoskeleton assistance on metabolic rate during walking.

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Jackson, Rachel W; Dembia, Christopher L; Delp, Scott L; Collins, Steven H

2017-06-01

The goal of this study was to gain insight into how ankle exoskeletons affect the behavior of the plantarflexor muscles during walking. Using data from previous experiments, we performed electromyography-driven simulations of musculoskeletal dynamics to explore how changes in exoskeleton assistance affected plantarflexor muscle-tendon mechanics, particularly for the soleus. We used a model of muscle energy consumption to estimate individual muscle metabolic rate. As average exoskeleton torque was increased, while no net exoskeleton work was provided, a reduction in tendon recoil led to an increase in positive mechanical work performed by the soleus muscle fibers. As net exoskeleton work was increased, both soleus muscle fiber force and positive mechanical work decreased. Trends in the sum of the metabolic rates of the simulated muscles correlated well with trends in experimentally observed whole-body metabolic rate ( R 2 =0.9), providing confidence in our model estimates. Our simulation results suggest that different exoskeleton behaviors can alter the functioning of the muscles and tendons acting at the assisted joint. Furthermore, our results support the idea that the series tendon helps reduce positive work done by the muscle fibers by storing and returning energy elastically. We expect the results from this study to promote the use of electromyography-driven simulations to gain insight into the operation of muscle-tendon units and to guide the design and control of assistive devices. © 2017. Published by The Company of Biologists Ltd.

RENAL DENERVATION IN RESISTANT ARTERIAL HYPERTENSION

Directory of Open Access Journals (Sweden)

V. A. Sulimov

2013-01-01

Full Text Available A new method of non-drug treatment of resistant hypertension – renal denervation is considered. General information about resistant hypertension, method of renal denervation, the results of clinical studies on efficacy and safety, as well as own clinical case are presented.

RENAL DENERVATION IN RESISTANT ARTERIAL HYPERTENSION

Directory of Open Access Journals (Sweden)

V. A. Sulimov

2015-09-01

Full Text Available A new method of non-drug treatment of resistant hypertension – renal denervation is considered. General information about resistant hypertension, method of renal denervation, the results of clinical studies on efficacy and safety, as well as own clinical case are presented.

IGF-II is up-regulated and myofibres are hypertrophied in regenerating soleus of mice lacking FGF6

International Nuclear Information System (INIS)

Armand, Anne-Sophie; Lecolle, Sylvie; Launay, Thierry; Pariset, Claude; Fiore, Frederic; Della Gaspera, Bruno; Birnbaum, Daniel; Chanoine, Christophe; Charbonnier, Frederic

2004-01-01

Important functions in myogenesis have been proposed for FGF6, a member of the fibroblast growth factor family accumulating almost exclusively in the myogenic lineage. However, the use of FGF6(-/-) mutant mice gave contradictory results and the role of FGF6 during myogenesis remains largely unclear. Using FGF6(-/-) mice, we first analysed the morphology of the regenerated soleus following cardiotoxin injection and showed hypertrophied myofibres in soleus of the mutant mice as compared to wild-type mice. Secondly, to examine the function of the IGF family in the hypertrophy process, we used semiquantitative and real-time RT-PCR assays and Western blots to monitor the expression of the insulin-like growth factors (IGF-I and IGF-II), their receptors [type I IGF receptor (IGF1R) and IGF-II receptor (IGF2R)], and of a binding protein IGFBP-5 in regenerating soleus muscles of FGF6(-/-) knockout mice vs. wild-type mice. In the mutant, both IGF-II and IGF2R, but not IGF-I and IGF1R, were strongly up-regulated, whereas IGFBP5 was down-regulated, strongly suggesting that, in the absence of FGF6, the mechanisms leading to myofibre hypertrophy were mediated specifically by an IGF-II/IGF2R signalling pathway distinct from the classic mechanism involving IGF-I and IGF1R previously described for skeletal muscle hypertrophy. The potential regulating role of IGFBP5 on IGF-II expression is also discussed. This report shows for the first time a specific role for FGF6 in the regulation of myofibre size during a process of in vivo myogenesis

Renal denervation: Results of a single-center cohort study

International Nuclear Information System (INIS)

Luetkens, J.A.; Thomas, D.; Doerner, J.; Schild, H.H.; Naehle, C.P.; Woitas, R.P.; Hundt, F.

2015-01-01

To investigate the effect of renal denervation on office-based and 24-h ambulatory blood pressure measurements (ABPM) in a highly selective patient population with drug-resistant hypertension. Patients with drug resistant hypertension eligible for renal denervation were included in the study population. Office blood pressure and ABPM were assessed prior to and after renal denervation. To detect procedure related renal or renal artery damage, magnetic resonance imaging (MRI) and angiography (MRA) were performed pre-interventional, one day post-interventional, and one month after renal denervation. Mean follow-up time between renal denervation and blood pressure re-assessment was 9.5 ± 3.9 months. Between August 2011 and March 2013, 17 patients prospectively underwent renal denervation. Pre-interventional mean office blood pressure and ABPM were 177.3 ± 20.3/103.8 ± 20.4 mmHg and 155.2 ± 20.5/93.7 ± 14.5 mmHg, respectively. Post-interventional, office blood pressure was significantly reduced to 144.7 ± 14.9/89.5 ± 12.1 (p 0.05). The number of prescribed antihypertensive drugs was unchanged after renal denervation (4.7 ± 2.0 vs. 4.2 ± 1.2, p = 0.18). No renovascular complications were detected in follow-up MRI. After renal denervation, no significant decrease in ABPM was observed. These results may indicate a limited impact of renal denervation for drug resistant hypertension.

Expression of interleukin-15 in human skeletal muscle effect of exercise and muscle fibre type composition

DEFF Research Database (Denmark)

Nielsen, Anders Rinnov; Mounier, Remi; Plomgaard, Peter

2007-01-01

The cytokine interleukin-15 (IL-15) has been demonstrated to have anabolic effects in cell culture systems. We tested the hypothesis that IL-15 is predominantly expressed by type 2 skeletal muscle fibres, and that resistance exercise regulates IL-15 expression in muscle. Triceps brachii, vastus...... lateralis quadriceps and soleus muscle biopsies were obtained from normally physically active, healthy, young male volunteers (n = 14), because these muscles are characterized by having different fibre-type compositions. In addition, healthy, normally physically active male subjects (n = 8) not involved...

Combined effect of space flight and radiation on skeletal muscles of rats

International Nuclear Information System (INIS)

Ilyina-Kakueva, E.I.; Portugalov, V.V.

1977-01-01

Skeletal muscles of rats flown for 20.5 d aboard the biosatellite Cosmos-690 and irradiated with a dose of 800 rads on the 10th flight day were studied. The radiation exposure aggravated the severity of atrophic and dystrophic processes in m. soleus and atrophic process in m. gastrocnemius that developed under the conditions of weightlessness and hypokinesia. At the same time, an exposure to penetrating radiation did not affect the muscles where no flight-induced pathologies occurred. The radiation affected the pattern of reparation in those regions of the soleus muscle that developed pathology inflight, slowed down resorption of the connective tissue formed during the pathological process, and inhibited the course of the reparative process

Fast-twitch glycolytic skeletal muscle is predisposed to age-induced impairments in mitochondrial function

DEFF Research Database (Denmark)

Jacobs, Robert A; Díaz, Víctor; Soldini, Lavinia

2013-01-01

The etiology of mammalian senescence is suggested to involve the progressive impairment of mitochondrial function; however, direct observations of age-induced alterations in actual respiratory chain function are lacking. Accordingly, we assessed mitochondrial function via high-resolution respirom......The etiology of mammalian senescence is suggested to involve the progressive impairment of mitochondrial function; however, direct observations of age-induced alterations in actual respiratory chain function are lacking. Accordingly, we assessed mitochondrial function via high......-resolution respirometry and mitochondrial protein expression in soleus, quadricep, and lateral gastrocnemius skeletal muscles, which represent type 1 slow-twitch oxidative muscle (soleus) and type 2 fast-twitch glycolytic muscle (quadricep and gastrocnemius), respectively, in young (10-12 weeks) and mature (74-76 weeks......) mice. Electron transport through mitochondrial complexes I and III increases with age in quadricep and gastrocnemius, which is not observed in soleus. Mitochondrial coupling efficiency during respiration through complex I also deteriorates with age in gastrocnemius and shows a tendency (p = .085...

Electromyographic analysis of an eccentric calf muscle exercise in persons with and without Achilles tendinopathy.

Science.gov (United States)

Reid, Duncan; McNair, Peter J; Johnson, Shelley; Potts, Geoff; Witvrouw, Erik; Mahieu, Nele

2012-08-01

To compare surface electromyographic (EMG) activity of the gastrocnemius and soleus muscles between persons with and without Achilles tendinopathy (AT) during an eccentric muscle exercise in different knee joint positions. Repeated measures design. Research laboratory. Participants (n = 18) diagnosed with AT and 18 control subjects were recruited. Gastrocnemius and soleus muscle activity was examined by surface (EMG) during extended and flexed knee joint conditions while performing the eccentric training technique. The EMG data were expressed as a percentage of a maximum voluntary contraction (MVC). EMG activity was notably higher (mean difference: 10%, effect size: 0.59) in those subjects with AT. Irrespective of the presence of AT, there was a significant interaction effect between muscle and joint position. The gastrocnemius muscle was significantly more active in the extended knee condition and soleus muscle activity was unchanged across joint positions. The results indicated that the presence of AT influenced calf muscle activity levels during performance of the eccentric exercise. There were differences in muscle activity during the extended and flexed knee conditions. This result does support performing Alfredson, Pietila, Jonsson, and Lorentzon (1998) eccentric exercise in an extended knee position but the specific effects of the knee flexed position on the Achilles tendon during eccentric exercise have yet to be determined, particularly in those with AT. Copyright © 2011 Elsevier Ltd. All rights reserved.

Tissue-specific and substrate-specific mitochondrial bioenergetics in feline cardiac and skeletal muscles

DEFF Research Database (Denmark)

Christiansen, Liselotte Bruun; Dela, Flemming; Koch, Jørgen

2015-01-01

fibers. Biopsies of left ventricular cardiac muscle and soleus muscle, a type I-rich oxidative skeletal muscle, were obtained from 15 healthy domestic cats. Enzymatic activity of citrate synthase (CS), a biomarker of mitochondrial content, was measured. Mitochondrial OXPHOS capacity with various kinds...

Endpoint design for future renal denervation trials - Novel implications for a new definition of treatment response to renal denervation.

Science.gov (United States)

Lambert, Thomas; Nahler, Alexander; Rohla, Miklos; Reiter, Christian; Grund, Michael; Kammler, Jürgen; Blessberger, Hermann; Kypta, Alexander; Kellermair, Jörg; Schwarz, Stefan; Starnawski, Jennifer A; Lichtenauer, Michael; Weiss, Thomas W; Huber, Kurt; Steinwender, Clemens

2016-10-01

Defining an adequate endpoint for renal denervation trials represents a major challenge. A high inter-individual and intra-individual variability of blood pressure levels as well as a partial or total non-adherence on antihypertensive drugs hamper treatment evaluations after renal denervation. Blood pressure measurements at a single point in time as used as primary endpoint in most clinical trials on renal denervation, might not be sufficient to discriminate between patients who do or do not respond to renal denervation. We compared the traditional responder classification (defined as systolic 24-hour blood pressure reduction of -5mmHg six months after renal denervation) with a novel definition of an ideal respondership (based on a 24h blood pressure reduction at no point in time, one, or all follow-up timepoints). We were able to re-classify almost a quarter of patients. Blood pressure variability was substantial in patients traditionally defined as responders. On the other hand, our novel classification of an ideal respondership seems to be clinically superior in discriminating sustained from pseudo-response to renal denervation. Based on our observations, we recommend that the traditional response classification should be reconsidered and possibly strengthened by using a composite endpoint of 24h-BP reductions at different follow-up-visits. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The arrangement of muscle fibers and tendons in two muscles used for growth studies.

Science.gov (United States)

Stickland, N C

1983-01-01

The arrangement of muscle fibres and tendons was examined in the soleus muscle of rats from 6 to 175 days post partum. The muscle was seen to change from a simple structure, with mean fibre length of approximately 90% of complete muscle length, to a unipennate structure, with mean fibre length of only about 60% of muscle length. The dog pectineus muscle was also investigated and found to have a bipennate structure throughout postnatal growth. The arrangement of muscle fibres in both these muscles is such that it might be difficult (particularly in the older animals) to cut a transverse section through all the fibres contained in the muscle; some fibres might not enter the plane of section. Results on muscle fibre number in these muscles at different ages may therefore be misleading.

Developmental changes in the activation properties and ultrastructure of fast- and slow-twitch muscles from fetal sheep.

Science.gov (United States)

West, J M; Barclay, C J; Luff, A R; Walker, D W

1999-04-01

At early stages of muscle development, skeletal muscles contract and relax slowly, regardless of whether they are destined to become fast- or slow-twitch. In this study, we have characterised the activation profiles of developing fast- and slow-twitch muscles from a precocial species, the sheep, to determine if the activation profiles of the muscles are characteristically slow when both the fast- and slow-twitch muscles have slow isometric contraction profiles. Single skinned muscle fibres from the fast-twitch flexor digitorum longus (FDL) and slow-twitch soleus muscles from fetal (gestational ages 70, 90, 120 and 140 days; term 147 days) and neonatal (8 weeks old) sheep were used to determine the isometric force-pCa (pCa = -log10[Ca2+]) and force-pSr relations during development. Fast-twitch mammalian muscles generally have a greatly different sensitivity to Ca2+ and Sr2+ whereas slow-twitch muscles have a similar sensitivity to these divalent cations. At all ages studied, the force-pCa and force-pSr relations of the FDL muscle were widely separated. The mean separation of the mid-point of the curves (pCa50-pSr50) was approximately 1.1. This is typical of adult fast-twitch muscle. The force-pCa and force-pSr curves for soleus muscle were also widely separated at 70 and 90 days gestation (pCa50-pSr50 approximately 0.75); between 90 days and 140 days this separation decreased significantly to approximately 0.2. This leads to a paradoxical situation whereby at early stages of muscle development the fast muscles have contraction dynamics of slow muscles but the slow muscles have activation profiles more characteristic of fast muscles. The time course for development of the FDL and soleus is different, based on sarcomere structure with the soleus muscle developing clearly defined sarcomere structure earlier in gestation than the FDL. At 70 days gestation the FDL muscle had no clearly defined sarcomeres. Force (N cm-2) increased almost linearly between 70 and 140 days

Mechano- and metabosensitive alterations after injection of botulinum toxin into gastrocnemius muscle.

Science.gov (United States)

Caron, Guillaume; Rouzi, Talifujiang; Grelot, Laurent; Magalon, Guy; Marqueste, Tanguy; Decherchi, Patrick

2014-07-01

This study was designed to investigate effects of motor denervation by Clostridium botulinum toxin serotype A (BoNT/A) on the afferent activity of fibers originating from the gastrocnemius muscle of rats. Animals were randomized in two groups, 1) untreated animals acting as control and 2) treated animals in which the toxin was injected in the left muscle. Locomotor activity was evaluated once per day during 12 days with a test based on footprint measurements of walking rats (sciatic functional index). At the end of the functional assessment period, electrophysiological tests were used to measure muscle properties, metabosensitive afferent fiber responses to chemical (KCl and lactic acid) injections, electrically induced fatigue (EIF), and mechanosensitive responses to tendon vibrations. Additionally, ventilatory response was recorded during repetitive muscle contractions. Then, rats were sacrificed, and the BoNT/A-injected muscles were weighed. Twelve days postinjection we observed a complete motor denervation associated with a significant muscle atrophy and loss of force to direct muscle stimulation. In the BoNT/A group, the metabosensitive responses to KCl injections were unaltered. However, we observed alterations in responses to EIF and to 1 mM of lactic acid (which induces the greatest activation). The ventilatory adjustments during repetitive muscle activation were abolished, and the mechanosensitive fiber responses to tendon vibrations were reduced. These results indicate that BoNT/A alters the sensorimotor loop and may induce insufficient motor and physiological adjustments in patients in whom a motor denervation with BoNT/A was performed. Copyright © 2014 Wiley Periodicals, Inc.

Renal denervation: a new therapeutic approach for resistant hypertension.

Science.gov (United States)

Cao, Longxing; Fu, Qiang; Wang, Binghui; Li, Zhiliang

2014-01-01

To review the advances in studies on renal denervation. References concerning renal denervation and resistant hypertension cited in this review were collected from PubMed published in English and those of renal denervation devices from official websites of device manufacturers up to January 2014. Articles with keywords "renal denervation" and "resistant hypertension" were selected. Renal and systemic sympathetic overactivity plays an important role in pathology of hypertension as well as other diseases characterized by sympathetic overactivity. Renal denervation is a new, catheter based procedure to reduce renal and systemic sympathetic overactivity by disruption of renal sympathetic efferent and afferent nerves through radiofrequency or ultrasound energy delivered to the endoluminal surface of both renal arteries. Although several studies have shown the efficacy and safety of renal denervation in the treatment of resistant hypertension and the potential benefit of the procedure in other diseases, Symplicity HTN 3 study, the most rigorous clinical trial of renal denervation to date, failed to meet its primary endpoint. The procedure also has other limitations such as the lack of long term, efficacy and safety data and the lack of the predictors for the blood pressure lowering response and nonresponse to the procedure. An overview of current renal denervation devices holding Conformité Européenne mark is also included in this review. Renal denervation is a promising therapeutic approach in the management of resistant hypertension and other diseases characterized by sympathetic overactivity. In its early stage of clinical application, the efficacy of the procedure is still controversial. Large scale, blind, randomized, controlled clinical trials are still necessary to address the limitations of the procedure.

Jumping in aquatic environment after sciatic nerve compression: nociceptive evaluation and morphological characteristics of the soleus muscle of Wistar rats.

Science.gov (United States)

Malanotte, Jéssica Aline; Kakihata, Camila Mayumi Martin; Karvat, Jhenifer; Brancalhão, Rose Meire Costa; Ribeiro, Lucinéia de Fátima Chasko; Bertolini, Gladson Ricardo Flor

2017-01-01

To evaluate the effect of jumping in aquatic environment on nociception and in the soleus muscle of trained and not trained Wistar rats, in the treatment of compressive neuropathy of the sciatic nerve. Twenty-five Wistar rats were distributed into five groups: Control, Lesion, Trained + Lesion, Lesion + Exercise, and Trained + Lesion + Exercise. The training was jumping exercise in water environment for 20 days prior to injury, and treatment after the injury. Nociception was evaluated in two occasions, before injury and seven after injury. On the last day of the experiment, the right soleus muscles were collected, processed and analyzed as to morphology and morphometry. In the assessment of nociception in the injury site, the Control Group had higher average than the rest, and the Lesion Group was larger than the Trained + Lesion and Lesion + Exercise Groups. The Control Group showed higher nociceptive threshold in paw, compared to the others. In the morphometric analysis, in relation to Control Group, all the injured groups showed decreased muscle fiber area, and in the Lesion Group was lower than in the Lesion + Exercise Group and Trained + Lesion Group. Considering the diameter of the muscle fiber, the Control Group had a higher average than the Trained + Lesion Group and the Trained + Lesion + Exercise Group; and the Lesion Group showed an average lower than the Trained + Lesion and Lesion + Exercise Groups. Resistance exercise produced increased nociception. When performed prior or after nerve damage, it proved effective in avoiding hypotrophy. The combination of the two protocols led to decrease in diameter and area of the muscle fiber. Avaliar os efeitos do salto em meio aquático, na nocicepção e no músculo sóleo, em ratos Wistar treinados e não treinados, no tratamento de neuropatia compressiva do nervo isquiático. Foram distribuídos em cinco grupos 25 ratos Wistar: Controle, Lesão, Treinado + Lesão, Lesão + Exercício e Treinado + Lesão + Exerc

Beta-adrenoceptor-agonist and insulin actions on glucose metabolism in rat skeletal muscle in different thyroid states.

OpenAIRE

Dimitriadis, G D; Richards, S J; Parry-Billings, M; Leighton, B; Newsholme, E A; Challiss, R A

1991-01-01

1. The actions of the beta-adrenoceptor agonist isoprenaline on glucose and glycogen metabolism, in the presence of various concentrations of insulin, were investigated in isolated soleus muscle preparations taken from eu-, hyper- and hypothyroid rats. 2. Hyperthyroidism, induced by 3,3',5-tri-iodo-D-thyronine (T3) administration for 5 days, increased the rate of lactate formation and suppressed the rate of glycogen synthesis in soleus muscle in response to isoprenaline, even in the presence ...

Onset of rigor mortis is earlier in red muscle than in white muscle.

Science.gov (United States)

Kobayashi, M; Takatori, T; Nakajima, M; Sakurada, K; Hatanaka, K; Ikegaya, H; Matsuda, Y; Iwase, H

2000-01-01

Rigor mortis is thought to be related to falling ATP levels in muscles postmortem. We measured rigor mortis as tension determined isometrically in three rat leg muscles in liquid paraffin kept at 37 degrees C or 25 degrees C--two red muscles, red gastrocnemius (RG) and soleus (SO) and one white muscle, white gastrocnemius (WG). Onset, half and full rigor mortis occurred earlier in RG and SO than in WG both at 37 degrees C and at 25 degrees C even though RG and WG were portions of the same muscle. This suggests that rigor mortis directly reflects the postmortem intramuscular ATP level, which decreases more rapidly in red muscle than in white muscle after death. Rigor mortis was more retarded at 25 degrees C than at 37 degrees C in each type of muscle.

Effects of exercise training on circulating and skeletal muscle renin-angiotensin system in chronic heart failure rats.

Science.gov (United States)

Gomes-Santos, Igor Lucas; Fernandes, Tiago; Couto, Gisele Kruger; Ferreira-Filho, Julio César Ayres; Salemi, Vera Maria Cury; Fernandes, Fernanda Barrinha; Casarini, Dulce Elena; Brum, Patricia Chakur; Rossoni, Luciana Venturini; de Oliveira, Edilamar Menezes; Negrao, Carlos Eduardo

2014-01-01

Accumulated evidence shows that the ACE-AngII-AT1 axis of the renin-angiotensin system (RAS) is markedly activated in chronic heart failure (CHF). Recent studies provide information that Angiotensin (Ang)-(1-7), a metabolite of AngII, counteracts the effects of AngII. However, this balance between AngII and Ang-(1-7) is still little understood in CHF. We investigated the effects of exercise training on circulating and skeletal muscle RAS in the ischemic model of CHF. Male Wistar rats underwent left coronary artery ligation or a Sham operation. They were divided into four groups: 1) Sedentary Sham (Sham-S), 2) exercise-trained Sham (Sham-Ex), sedentary CHF (CHF-S), and exercise-trained CHF (CHF-Ex). Angiotensin concentrations and ACE and ACE2 activity in the circulation and skeletal muscle (soleus and plantaris) were quantified. Skeletal muscle ACE and ACE2 protein expression, and AT1, AT2, and Mas receptor gene expression were also evaluated. CHF reduced ACE2 serum activity. Exercise training restored ACE2 and reduced ACE activity in CHF. Exercise training reduced plasma AngII concentration in both Sham and CHF rats and increased the Ang-(1-7)/AngII ratio in CHF rats. CHF and exercise training did not change skeletal muscle ACE and ACE2 activity and protein expression. CHF increased AngII levels in both soleus and plantaris muscle, and exercise training normalized them. Exercise training increased Ang-(1-7) in the plantaris muscle of CHF rats. The AT1 receptor was only increased in the soleus muscle of CHF rats, and exercise training normalized it. Exercise training increased the expression of the Mas receptor in the soleus muscle of both exercise-trained groups, and normalized it in plantaris muscle. Exercise training causes a shift in RAS towards the Ang-(1-7)-Mas axis in skeletal muscle, which can be influenced by skeletal muscle metabolic characteristics. The changes in RAS circulation do not necessarily reflect the changes occurring in the RAS of skeletal

The influence of flow redistribution on working rat muscle oxygenation.

NARCIS (Netherlands)

Hoofd, L.J.C.; Degens, H.

2009-01-01

We applied a theoretical model of muscle tissue O2 transport to investigate the effects of flow redistribution on rat soleus muscle oxygenation. The situation chosen was the anaerobic threshold where redistribution of flow is expected to have the largest impact. In the basic situation all

The effects of elevated levels of sodium bicarbonate (NaHCO₃) on the acute power output and time to fatigue of maximally stimulated mouse soleus and EDL muscles.

Science.gov (United States)

Higgins, M F; Tallis, J; Price, M J; James, R S

2013-05-01

This study examined the effects of elevated buffer capacity [~32 mM HCO₃(-)] through administration of sodium bicarbonate (NaHCO₃) on maximally stimulated isolated mouse soleus (SOL) and extensor digitorum longus (EDL) muscles undergoing cyclical length changes at 37 °C. The elevated buffering capacity was of an equivalent level to that achieved in humans with acute oral supplementation. We evaluated the acute effects of elevated [HCO₃(-)] on (1) maximal acute power output (PO) and (2) time to fatigue to 60 % of maximum control PO (TLIM60), the level of decline in muscle PO observed in humans undertaking similar exercise, using the work loop technique. Acute PO was on average 7.0 ± 4.8 % greater for NaHCO₃-treated EDL muscles (P < 0.001; ES = 2.0) and 3.6 ± 1.8 % greater for NaHCO₃-treated SOL muscles (P < 0.001; ES = 2.3) compared to CON. Increases in PO were likely due to greater force production throughout shortening. The acute effects of NaHCO₃ on EDL were significantly greater (P < 0.001; ES = 0.9) than on SOL. Treatment of EDL (P = 0.22; ES = 0.6) and SOL (P = 0.19; ES = 0.9) with NaHCO₃ did not alter the pattern of fatigue. Although significant differences were not observed in whole group data, the fatigability of muscle performance was variable, suggesting that there might be inter-individual differences in response to NaHCO₃ supplementation. These results present the best indication to date that NaHCO₃ has direct peripheral effects on mammalian skeletal muscle resulting in increased acute power output.

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

OpenAIRE

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

2016-01-01

This study demonstrates, for the first time, adaptive plastic changes in the stretch reflex circuitry following denervation induced by botulinum toxin injection. The study also demonstrates alterations of the elastic properties of the muscles following botulinum injection.

Evidence that the Na+-K+ leak/pump ratio contributes to the difference in endurance between fast- and slow-twitch muscles.

Science.gov (United States)

Clausen, T; Overgaard, K; Nielsen, O B

2004-02-01

Muscles containing predominantly fast-twitch (type II) fibres [ext. dig. longus (EDL)] show considerably lower contractile endurance than muscles containing mainly slow-twitch (type I) fibres (soleus). To assess whether differences in Na+-K+ fluxes and excitability might contribute to this phenomenon, we compared excitation-induced Na+-K+ leaks, Na+ channels, Na+-K+ pump capacity, force and compound action potentials (M-waves) in rat EDL and soleus muscles. Isolated muscles were mounted for isometric contractions in Krebs-Ringer bicarbonate buffer and exposed to direct or indirect continuous or intermittent electrical stimulation. The time-course of force decline and concomitant changes in Na+-K+ exchange and M-waves were recorded. During continuous stimulation at 60-120 Hz, EDL showed around fivefold faster rate of force decline than soleus. This was associated with a faster loss of excitability as estimated from the area and amplitude of the M-waves. The net uptake of Na+ and the release of K+ per action potential were respectively 6.5- and 6.6-fold larger in EDL than in soleus, which may in part be due to the larger content of Na+ channels in EDL. During intermittent stimulation with 1 s 60 Hz pulse trains, EDL showed eightfold faster rate of force decline than soleus. The considerably lower contractile endurance of fast-twitch compared with slow-twitch muscles reflects differences in the rate of excitation-induced loss of excitability. This is attributed to the much larger excitation-induced Na+ influx and K+ efflux, leading to a faster rise in [K+]o in fast-twitch muscles. This may only be partly compensated by the concomitant activation of the Na+-K+ pumps, in particular in fibres showing large passive Na+-K+ leaks or reduced content of Na+-K+ pumps. Thus, endurance depends on the leak/pump ratio for Na+ and K+.

The role of muscle imbalance in the pathogenesis of shoulder contracture after neonatal brachial plexus palsy: a study in a rat model.

Science.gov (United States)

Soldado, Francisco; Fontecha, Cesar G; Marotta, Mario; Benito, David; Casaccia, Marcelo; Mascarenhas, Vasco V; Zlotolow, Dan; Kozin, Scott H

2014-07-01

An internal rotation contracture of the shoulder is common after neonatal brachial plexus injuries due to subscapularis shortening and atrophy. It has been explained by 2 theories: muscle denervation and muscle imbalance between the internal and external rotators of the shoulder. The goal of this study was to test the hypothesis that muscle imbalance alone could cause subscapularis changes and shoulder contracture. We performed selective neurectomy of the suprascapular nerve in 15 newborn rats to denervate only the supraspinatus and the infraspinatus muscles, leaving the subscapularis muscle intact. After 4 weeks, passive shoulder external rotation was measured and a 7.2-T magnetic resonance imaging scan of the shoulders was used to determine changes in the infraspinatus and subscapularis muscles. The subscapularis muscle was weighed to determine the degree of mass loss. An additional group of 10 newborn rats was evaluated to determine the sectional muscle fiber size and muscle area of fibrosis by use of images from type I collagen immunostaining. There was a significant decrease in passive shoulder external rotation, with a mean loss of 66°; in the thickness of the denervated infraspinatus, with a mean loss of 40%; and in the thickness and weight of the non-denervated subscapularis, with mean losses of 28% and 25%, respectively. No differences were found in subscapularis muscle fiber size and area of fibrosis between shoulders after suprascapular nerve injury. Our study supports the theory that shoulder muscle imbalance is a cause of shoulder contracture in patients with neonatal brachial plexus palsy. Copyright © 2014 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.

Renal denervation: What happened, and why?

Science.gov (United States)

Shishehbor, Mehdi H; Hammad, Tarek A; Thomas, George

2017-09-01

Despite promising results in initial trials, renal denervation failed to achieve its efficacy end points as a treatment for resistant hypertension in the SYMPLICITY HTN-3 trial, the largest trial of this treatment to date (N Engl J Med 2014; 370:1393-1401). Is renal denervation dead, or will future trials and newer technology revive it? Copyright © 2017 Cleveland Clinic.

Renal sympathetic denervation in hypertension.

Science.gov (United States)

Doumas, Michael; Faselis, Charles; Papademetriou, Vasilios

2011-11-01

Despite the abundance of antihypertensive drugs, resistant hypertension remains a major clinical problem. Recent technological advances render interventional management of resistant hypertension one of the hottest topics in the hypertension field. The aim of this review is to present the pathophysiologic background and the mechanisms mediating blood pressure reduction after renal sympathetic denervation, to analyze recent findings with this fascinating approach and to critically suggest future research directions. Catheter-based, ablation-induced renal sympathetic denervation was initially studied in 45 patients with resistant hypertension in a proof-of-concept study. Impressive blood pressure reductions of about 30/15  mmHg were achieved at 6 months, without serious complications. A second, controlled, randomized (but not blinded) study confirmed the results, verifying the efficacy and safety of the procedure. A recent report revealed the 2-year durability of blood pressure reduction. Data published so far indicate that ablation-induced renal denervation is a feasible, effective, and well tolerated interventional approach for the management of resistant hypertension. The groundbreaking studies of renal denervation in drug-resistant hypertension pave the way for further research in other disease conditions in which sympathetic overactivity seems to play a critical role. This initial wave of enthusiasm needs to be followed by rigorous investigation, for the proper identification of the potential and the limitations, indications, and contraindications of this approach.

Postural adjustments associated with voluntary contraction of leg muscles in standing man.

Science.gov (United States)

Nardone, A; Schieppati, M

1988-01-01

The postural adjustments associated with a voluntary contraction of the postural muscles themselves have been studied in the legs of normal standing men. We focussed on the following questions. Do postural adjustments precede the focal movement as in the case of movements of the upper limb? Which muscle(s) are involved in the task of stabilizing posture? Can the same postural muscle be activated in postural stabilization and in voluntary movement at the same time, in spite of the opposite changes in activity possibly required by these conditions? Six subjects standing on a dynamometric platform were asked to rise onto the tips their toes by contracting their soleus muscles, or to rock on their heels by contracting their tibialis anterior muscles. The tasks were made in a reaction time (RT) situation or in a self-paced mode, standing either freely or holding onto a stable structure. Surface EMGs of leg and thigh muscles, and the foot-floor reaction forces were recorded. The following results were obtained in the RT mode, standing freely. 1. Rising onto toe tips: a striking silent period in soleus preceded its voluntary activation; during this silent period, a tibialis anterior burst could be observed in three subjects; these anticipatory activities induced a forward sway, as monitored by a change in the force exerted along the x axis of the platform. 2. Rocking on heels: an enhancement in tonic EMG of soleus was observed before tibialis anterior voluntary burst, at a mean latency from the go-signal similar to that of the silent period; this anticipatory activity induced a backward body sway. 3. Choice RT conditions showed that the above anticipatory patterns in muscle activity were pre-programmed, specific for the intended tasks, and closely associated with the focal movement. When both tasks were performed in a self-paced mode, all the above EMG and mechanical features were more pronounced and unfolded in time. If the subjects held onto the frame, the early

Proteomic and carbonylation profile analysis of rat skeletal muscles following acute swimming exercise.

Directory of Open Access Journals (Sweden)

Francesca Magherini

Full Text Available Previous studies by us and other groups characterized protein expression variation following long-term moderate training, whereas the effects of single bursts of exercise are less known. Making use of a proteomic approach, we investigated the effects of acute swimming exercise (ASE on protein expression and carbonylation patterns in two hind limb muscles: the Extensor Digitorum Longus (EDL and the Soleus, mostly composed of fast-twitch and slow-twitch fibres, respectively. Carbonylation is one of the most common oxidative modifications of proteins and a marker of oxidative stress. In fact, several studies suggest that physical activity and the consequent increase in oxygen consumption can lead to increase in reactive oxygen and nitrogen species (RONS production, hence the interest in examining the impact of RONS on skeletal muscle proteins following ASE. Results indicate that protein expression is unaffected by ASE in both muscle types. Unexpectedly, the protein carbonylation level was reduced following ASE. In particular, the analysis found 31 and 5 spots, in Soleus and EDL muscles respectively, whose carbonylation is reduced after ASE. Lipid peroxidation levels in Soleus were markedly reduced as well. Most of the decarbonylated proteins are involved either in the regulation of muscle contractions or in the regulation of energy metabolism. A number of hypotheses may be advanced to account for such results, which will be addressed in future studies.

Renal Denervation for Chronic Heart Failure: Background and Pathophysiological Rationale.

Science.gov (United States)

Böhm, Michael; Ewen, Sebastian; Mahfoud, Felix

2017-01-01

The activation of the sympathetic nervous system is associated with cardiovascular hospitalizations and death in heart failure. Renal denervation has been shown to effectively reduce sympathetic overdrive in certain patients with uncontrolled hypertension. Pilot trials investigating renal denervation as a potential treatment approach for heart failure were initiated. Heart failure comorbidities like obstructive sleep apnea, metabolic syndrome and arrhythmias could also be targets for renal denervation, because these occurrences are also mediated by the activation of the sympathetic nervous system. Therefore, renal denervation in heart failure is worthy of further investigation, although its effectiveness still has to be proven. Herein, we describe the pathophysiological rationale and the effect of renal denervation on surrogates of the heart failure syndrome.

Renal Sympathetic Denervation: Hibernation or Resurrection?

Science.gov (United States)

Papademetriou, Vasilios; Doumas, Michael; Tsioufis, Costas

The most current versions of renal sympathetic denervation have been invented as minimally invasive approaches for the management of drug-resistant hypertension. The anatomy, physiology and pathophysiology of renal sympathetic innervation provide a strong background supporting an important role of the renal nerves in the regulation of blood pressure (BP) and volume. In addition, historical data with surgical sympathectomy and experimental data with surgical renal denervation indicate a beneficial effect on BP levels. Early clinical studies with transcatheter radiofrequency ablation demonstrated impressive BP reduction, accompanied by beneficial effects in target organ damage and other disease conditions characterized by sympathetic overactivity. However, the failure of the SYMPLICITY 3 trial to meet its primary efficacy end point raised a lot of concerns and put the field of renal denervation into hibernation. This review aims to translate basic research into clinical practice by presenting the anatomical and physiological basis for renal sympathetic denervation, critically discussing the past and present knowledge in this field, where we stand now, and also speculating about the future of the intervention and potential directions for research. © 2016 S. Karger AG, Basel.

Muscle protein analysis. II. Two-dimensional electrophoresis of normal and diseased human skeletal muscle

Energy Technology Data Exchange (ETDEWEB)

Giometti, C.S. (Argonne National Lab., IL); Barany, M.; Danon, M.J.; Anderson, N.G.

1980-07-01

High-resolution two-dimensional electrophoresis was used to analyze the major proteins of normal and pathological human-muscle samples. The normal human-muscle pattern contains four myosin light chains: three that co-migrate with the myosin light chains from rabbit fast muscle (extensor digitorum longus), and one that co-migrates with the light chain 2 from rabbit slow muscle (soleus). Of seven Duchenne muscular dystrophy samples, four yielded patterns with decreased amounts of actin and myosin relative to normal muscle, while three samples gave patterns comparable to that for normal muscle. Six samples from patients with myotonic dystrophy also gave normal patterns. In nemaline rod myopathy, in contrast, the pattern was deficient in two of the fast-type myosin light chains.

Symplicity multi-electrode radiofrequency renal denervation system feasibility study.

Science.gov (United States)

Whitbourn, Robert; Harding, Scott A; Walton, Antony

2015-05-01

The aim of this study was to test the safety and performance of the Symplicity™ multi-electrode radio-frequency renal denervation system which was designed to reduce procedure time during renal denervation. The multi-electrode radiofrequency renal denervation system feasibility study is a prospective, non-randomised, open label, feasibility study that enrolled 50 subjects with hypertension. The study utilises a new renal denervation catheter which contains an array of four electrodes mounted in a helical configuration at 90 degrees from each other to deliver radiofrequency energy simultaneously to all four renal artery quadrants for 60 seconds. The protocol specified one renal denervation treatment towards the distal end of each main renal artery with radiofrequency energy delivered for 60 seconds per treatment. Total treatment time for both renal arteries was two minutes. The 12-month change in office systolic blood pressure (SBP) and 24-hour SBP was -19.2±25.2 mmHg, prenal artery stenosis or hypertensive emergencies occurred. The Symplicity multi-electrode radiofrequency renal denervation system was associated with a significant reduction in SBP at 12 months and minimal complications whilst it also reduced procedure time. NCT01699529.

Time Course of the Response of Myofibrillar and Sarcoplasmic Protein Metabolism to Unweighting of the Soleus Muscle

Science.gov (United States)

Munoz, Kathryn A.; Satarug, Soisungwan; Tischler, Marc E.

1993-01-01

Contributions of altered in vivo protein synthesis and degradation to unweighting atrophy of the soleus muscle in tail-suspended young female rats were analyzed daily for up to 6 days. Specific changes in myofibrillar and sarcoplasmic proteins were also evaluated to assess their contributions to the loss of total protein. Synthesis of myofibrillar and sarcoplasmic proteins was estimated by intramuscular (IM) injection and total protein by intraperitoneal (IP) injection of flooding doses of H-3-phenylaianine. Total protein loss was greatest during the first 3 days following suspension and was a consequence of the loss of myofibrillar rather than sarcoplasmic proteins. However, synthesis of total myofibrillar and sarcoplasmic proteins diminished in parallel beginning in the first 24 hours. Therefore sarcoplasmic proteins must be spared due to a decrease in their degradation. In contrast, myofibrillar protein degradation increased, thus explaining the elevated degradation of the total pool. Following 72 hours of suspension, protein synthesis remained low, but the rate of myofibrillar protein loss diminished, suggesting a slowing of degradation. These various results show acute loss of protein during unweighting atrophy is a consequence of decreased synthesis and increased degradation of myofibrillar proteins, and sarcoplasmic proteins are spared due to slower degradation, likely explaining the sparing of plasma membrane receptors. Based on other published data, we propose that the slowing of atrophy after the initial response may be attributed to an increased effect of insulin.

Renal Denervation for Chronic Heart Failure: Background and Pathophysiological Rationale

Science.gov (United States)

Ewen, Sebastian; Mahfoud, Felix

2017-01-01

The activation of the sympathetic nervous system is associated with cardiovascular hospitalizations and death in heart failure. Renal denervation has been shown to effectively reduce sympathetic overdrive in certain patients with uncontrolled hypertension. Pilot trials investigating renal denervation as a potential treatment approach for heart failure were initiated. Heart failure comorbidities like obstructive sleep apnea, metabolic syndrome and arrhythmias could also be targets for renal denervation, because these occurrences are also mediated by the activation of the sympathetic nervous system. Therefore, renal denervation in heart failure is worthy of further investigation, although its effectiveness still has to be proven. Herein, we describe the pathophysiological rationale and the effect of renal denervation on surrogates of the heart failure syndrome. PMID:28154583

Mitochondrial oxidative enzyme activity in individual fibre types in hypo- and hyperthyroid rat skeletal muscles.

Science.gov (United States)

Johnson, M A; Turnbull, D M

1984-04-01

Quantitative cytochemical and biochemical techniques have been used in combination to study the response of mitochondrial oxidative enzymes in individual muscle fibre types to hypo- and hyperthyroidism. Hypothyroidism resulted in decreased activity of succinate dehydrogenase (SDH), L-glycerol-3-phosphate dehydrogenase (L-GPDH), and D-3-hydroxybutyrate dehydrogenase (D-HBDH) in all fibre types of both slow-twitch soleus and fast-twitch extensor digitorum longus (e.d.l.) muscles. In hyperthyroidism, only L-GPDH activity increased in e.d.l. but more marked increases were seen in soleus muscles, which also showed increased SDH activity. In addition to these alterations in the enzyme activity in individual fibre types the metabolic profile of the muscle is further modified by the hormone-induced interconversion of slow- to fast-twitch fibres and vice versa.

The embryonic genes Dkk3, Hoxd8, Hoxd9 and Tbx1 identify muscle types in a diet-independent and fiber-type unrelated way

Directory of Open Access Journals (Sweden)

Boekschoten Mark V

2010-03-01

Full Text Available Abstract Background The mouse skeletal muscle is composed of four distinct fiber types that differ in contractile function, number of mitochondria and metabolism. Every muscle type has a specific composition and distribution of the four fiber types. To find novel genes involved in specifying muscle types, we used microarray analysis to compare the gastrocnemius with the quadriceps from mice fed a low fat diet (LFD or high fat diet (HFD for 8 weeks. Additional qPCR analysis were performed in the gastrocnemius, quadriceps and soleus muscle from mice fed an LFD or HFD for 20 weeks. Results In mice fed the 8-week LFD 162 genes were differentially expressed in the gastrocnemius vs. the quadriceps. Genes with the strongest differences in expression were markers for oxidative fiber types (e.g. Tnni1 and genes which are known to be involved in embryogenesis (Dkk3, Hoxd8,Hoxd9 and Tbx1. Also Dkk2, Hoxa5, Hoxa10, Hoxc9, Hoxc10, Hoxc6 and Tbx15 were detectably, but not differentially expressed in adult muscle tissue. Expression of differentially expressed genes was not influenced by an 8-week or 20-week HFD. Comparing gastrocnemius, quadriceps and soleus, expression of Hoxd8 and Hoxd9 was not related with expression of markers for the four different fiber types. We found that the expression of both Hoxd8 and Hoxd9 was much higher in the gastrocnemius than in the quadriceps or soleus, whereas the expression of Dkk3 was high in quadriceps, but low in both gastrocnemius and soleus. Finally, expression of Tbx1 was high in quadriceps, intermediate in soleus and low in gastrocnemius. Conclusions We found that genes from the Dkk family, Hox family and Tbx family are detectably expressed in adult mouse muscle. Interestingly, expression of Dkk3, Hoxd8, Hoxd9 and Tbx1 was highly different between gastrocnemius, quadriceps and soleus. In fact, every muscle type showed a unique combination of expression of these four genes which was not influenced by diet. Altogether

Use it or lose it: tonic activity of slow motoneurons promotes their survival and preferentially increases slow fiber-type groupings in muscles of old lifelong recreational sportsmen

Directory of Open Access Journals (Sweden)

Simone Mosole

2016-11-01

Full Text Available Histochemistry, immuno-histochemistry, gel electrophoresis of single muscle fibers and electromyography of aging muscles and nerves suggest that: i denervation contributes to muscle atrophy, ii impaired mobility accelerates the process, and iii lifelong running protects against loss of motor units. Recent corroborating results on the muscle effects of Functional Electrical Stimulation (FES of aged muscles will be also mentioned, but we will in particular discuss how and why a lifelong increased physical activity sustains reinnervation of muscle fibers. By analyzing distribution and density of muscle fibers co-expressing fast and slow Myosin Heavy Chains (MHC we are able to distinguish the transforming muscle fibers due to activity related plasticity, to those that adapt muscle fiber properties to denervation and reinnervation. In muscle biopsies from septuagenarians with a history of lifelong high-level recreational activity we recently observed in comparison to sedentary seniors: 1. decreased proportion of small-size angular myofibers (denervated muscle fibers; 2. considerable increase of fiber-type groupings of the slow type (reinnervated muscle fibers; 3. sparse presence of muscle fibers co-expressing fast and slow MHC. Immuno-histochemical characteristics fluctuate from those with scarce fiber-type modulation and groupings to almost complete transformed muscles, going through a process in which isolated fibers co-expressing fast and slow MHC fill the gaps among fiber groupings. Data suggest that lifelong high-level exercise allows the body to adapt to the consequences of the age-related denervation and that it preserves muscle structure and function by saving otherwise lost muscle fibers through recruitment to different slow motor units. This is an opposite behavior of that described in long term denervated or resting muscles. These effects of lifelong high level activity seems to act primarily on motor neurons, in particular on those always

Use it or Lose It: Tonic Activity of Slow Motoneurons Promotes Their Survival and Preferentially Increases Slow Fiber-Type Groupings in Muscles of Old Lifelong Recreational Sportsmen

Science.gov (United States)

Mosole, Simone; Carraro, Ugo; Kern, Helmut; Loefler, Stefan; Zampieri, Sandra

2016-01-01

Histochemistry, immuno-histochemistry, gel electrophoresis of single muscle fibers and electromyography of aging muscles and nerves suggest that: i) denervation contributes to muscle atrophy, ii) impaired mobility accelerates the process, and iii) lifelong running protects against loss of motor units. Recent corroborating results on the muscle effects of Functional Electrical Stimulation (FES) of aged muscles will be also mentioned, but we will in particular discuss how and why a lifelong increased physical activity sustains reinnervation of muscle fibers. By analyzing distribution and density of muscle fibers co-expressing fast and slow Myosin Heavy Chains (MHC) we are able to distinguish the transforming muscle fibers due to activity related plasticity, to those that adapt muscle fiber properties to denervation and reinnervation. In muscle biopsies from septuagenarians with a history of lifelong high-level recreational activity we recently observed in comparison to sedentary seniors: 1. decreased proportion of small-size angular myofibers (denervated muscle fibers); 2. considerable increase of fiber-type groupings of the slow type (reinnervated muscle fibers); 3. sparse presence of muscle fibers co-expressing fast and slow MHC. Immuno-histochemical characteristics fluctuate from those with scarce fiber-type modulation and groupings to almost complete transformed muscles, going through a process in which isolated fibers co-expressing fast and slow MHC fill the gaps among fiber groupings. Data suggest that lifelong high-level exercise allows the body to adapt to the consequences of the age-related denervation and that it preserves muscle structure and function by saving otherwise lost muscle fibers through recruitment to different slow motor units. This is an opposite behavior of that described in long term denervated or resting muscles. These effects of lifelong high level activity seems to act primarily on motor neurons, in particular on those always more active

Use it or Lose It: Tonic Activity of Slow Motoneurons Promotes Their Survival and Preferentially Increases Slow Fiber-Type Groupings in Muscles of Old Lifelong Recreational Sportsmen.

Science.gov (United States)

Mosole, Simone; Carraro, Ugo; Kern, Helmut; Loefler, Stefan; Zampieri, Sandra

2016-09-15

Histochemistry, immuno-histochemistry, gel electrophoresis of single muscle fibers and electromyography of aging muscles and nerves suggest that: i) denervation contributes to muscle atrophy, ii) impaired mobility accelerates the process, and iii) lifelong running protects against loss of motor units. Recent corroborating results on the muscle effects of Functional Electrical Stimulation (FES) of aged muscles will be also mentioned, but we will in particular discuss how and why a lifelong increased physical activity sustains reinnervation of muscle fibers. By analyzing distribution and density of muscle fibers co-expressing fast and slow Myosin Heavy Chains (MHC) we are able to distinguish the transforming muscle fibers due to activity related plasticity, to those that adapt muscle fiber properties to denervation and reinnervation. In muscle biopsies from septuagenarians with a history of lifelong high-level recreational activity we recently observed in comparison to sedentary seniors: 1. decreased proportion of small-size angular myofibers (denervated muscle fibers); 2. considerable increase of fiber-type groupings of the slow type (reinnervated muscle fibers); 3. sparse presence of muscle fibers co-expressing fast and slow MHC. Immuno-histochemical characteristics fluctuate from those with scarce fiber-type modulation and groupings to almost complete transformed muscles, going through a process in which isolated fibers co-expressing fast and slow MHC fill the gaps among fiber groupings. Data suggest that lifelong high-level exercise allows the body to adapt to the consequences of the age-related denervation and that it preserves muscle structure and function by saving otherwise lost muscle fibers through recruitment to different slow motor units. This is an opposite behavior of that described in long term denervated or resting muscles. These effects of lifelong high level activity seems to act primarily on motor neurons, in particular on those always more active

Contribution of sensory feedback to plantar flexor muscle activation during push-off in adults with cerebral palsy

DEFF Research Database (Denmark)

Frisk, Rasmus F.; Jensen, Peter; Kirk, Henrik

2017-01-01

applied unload perturbations at the ankle, thereby removing sensory feedback naturally activated during push-off. Reduction of electromyographic (EMG) activity in the soleus muscle caused by unloads was compared and related to kinematics and ankle joint stiffness measurements. Similar measures were...... feedback to ongoing soleus muscle activation during push-off than uninjured individuals. Increased passive stiffness around the ankle joint is likely to diminishn sensory feedback during gait, and/or sensory feedback is less integrated with central motor commands in the activation of spinal motor neurons...

Measurement of nucleotide exchange rate constants in single rabbit soleus myofibrils during shortening and lengthening using a fluorescent ATP analog.

Science.gov (United States)

Shirakawa, I; Chaen, S; Bagshaw, C R; Sugi, H

2000-02-01

The kinetics of displacement of a fluorescent nucleotide, 2'(3')-O-[N[2-[[Cy3]amido]ethyl]carbamoyl]-adenosine 5'-triphosphate (Cy3-EDA-ATP), bound to rabbit soleus muscle myofibrils were studied using flash photolysis of caged ATP. Use of myofibrils from this slow twitch muscle allowed better resolution of the kinetics of nucleotide exchange than previous studies with psoas muscle myofibrils (, Biophys. J. 73:2033-2042). Soleus myofibrils in the presence of Cy3-EDA-nucleotides (Cy3-EDA-ATP or Cy3-EDA-ADP) showed selective fluorescence staining of the A-band. The K(m) for Cy3-EDA-ATP and the K(d) for Cy3-EDA-ADP binding to the myofibril A-band were 1.9 microM and 3.8 microM, respectively, indicating stronger binding of nucleotide to soleus cross-bridges compared to psoas cross-bridges (2.6 microM and 50 microM, respectively). After flash photolysis of caged ATP, the A-band fluorescence of the myofibril in the Cy3-EDA-ATP solution under isometric conditions decayed exponentially with a rate constant of 0.045 +/- 0.007 s(-1) (n = 32) at 10 degrees C, which was about seven times slower than that for psoas myofibrils. When a myofibril was allowed to shorten with a constant velocity, the nucleotide displacement rate constant increased from 0.066 s(-1) (isometric) to 0.14 s(-1) at 20 degrees C with increasing shortening velocity up to 0.1 myofibril length/s (V(max), the shortening velocity under no load was approximately 0. 2 myofibril lengths/s). The rate constant was not significantly affected by an isovelocity stretch of up to 0.1 myofibril lengths/s. These results suggest that the cross-bridge kinetics are not significantly affected at higher strain during lengthening but depend on the lower strain during shortening. These data also indicate that the interaction distance between a cross-bridge and the actin filament is at least 16 nm for a single cycle of the ATPase.

Imaging of muscular denervation secondary to motor cranial nerve dysfunction

International Nuclear Information System (INIS)

Connor, S.E.J.; Chaudhary, N.; Fareedi, S.; Woo, E.K.

2006-01-01

The effects of motor cranial nerve dysfunction on the computed tomography (CT) and magnetic resonance imaging (MRI) appearances of head and neck muscles are reviewed. Patterns of denervation changes are described and illustrated for V, VII, X, XI and XII cranial nerves. Recognition of the range of imaging manifestations, including the temporal changes in muscular appearances and associated muscular grafting or compensatory hypertrophy, will avoid misinterpretation as local disease. It will also prompt the radiologist to search for underlying cranial nerve pathology, which may be clinically occult. The relevant cranial nerve motor division anatomy will be described to enable a focussed search for such a structural abnormality

Imaging of muscular denervation secondary to motor cranial nerve dysfunction

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Connor, S.E.J. [Neuroradiology Department, Kings College Hospital, Denmark Hill, London SE5 9RS (United Kingdom)]. E-mail: sejconnor@tiscali.co.uk; Chaudhary, N. [Neuroradiology Department, Kings College Hospital, Denmark Hill, London SE5 9RS (United Kingdom); Fareedi, S. [Neuroradiology Department, Kings College Hospital, Denmark Hill, London SE5 9RS (United Kingdom); Woo, E.K. [Neuroradiology Department, Kings College Hospital, Denmark Hill, London SE5 9RS (United Kingdom)

2006-08-15

The effects of motor cranial nerve dysfunction on the computed tomography (CT) and magnetic resonance imaging (MRI) appearances of head and neck muscles are reviewed. Patterns of denervation changes are described and illustrated for V, VII, X, XI and XII cranial nerves. Recognition of the range of imaging manifestations, including the temporal changes in muscular appearances and associated muscular grafting or compensatory hypertrophy, will avoid misinterpretation as local disease. It will also prompt the radiologist to search for underlying cranial nerve pathology, which may be clinically occult. The relevant cranial nerve motor division anatomy will be described to enable a focussed search for such a structural abnormality.

Renal denervation after Symplicity HTN-3: an update.

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Persu, Alexandre; Jin, Yu; Fadl Elmula, Fadl Elmula Mohamed; Jacobs, Lotte; Renkin, Jean; Kjeldsen, Sverre

2014-08-01

After three years of excessive confidence, overoptimistic expectations and performance of 15 to 20,000 renal denervation procedures in Europe, the failure of a single well-designed US trial--Symplicity HTN-3--to meet its primary efficacy endpoint has cast doubt on renal denervation as a whole. The use of a sound methodology, including randomisation and blinded endpoint assessment was enough to see the typical 25-30 mmHg systolic blood pressure decrease observed after renal denervation melt down to less than 3 mmHg, the rest being likely explained by Hawthorne and placebo effects, attenuation of white coat effect, regression to the mean and other physician and patient-related biases. The modest blood pressure benefit directly assignable to renal denervation should be balanced with unresolved safety issues, such as potentially increased risk of renal artery stenosis after the procedure (more than ten cases reported up to now, most of them in 2014), unclear long-term impact on renal function and lack of morbidity-mortality data. Accordingly, there is no doubt that renal denervation is not ready for clinical use. Still, renal denervation is supported by a strong rationale and is occasionally followed by major blood pressure responses in at-risk patients who may otherwise have remained uncontrolled. Upcoming research programmes should focus on identification of those few patients with truly resistant hypertension who may derive a substantial benefit from the technique, within the context of well-designed randomised trials and independent registries. While electrical stimulation of baroreceptors and other interventional treatments of hypertension are already "knocking at the door", the premature and uncontrolled dissemination of renal denervation should remain an example of what should not be done, and trigger radical changes in evaluation processes of new devices by national and European health authorities.

Increased Autolysis of μ-Calpain in Skeletal Muscles of Chronic Alcohol-Fed Rats.

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Gritsyna, Yulia V; Salmov, Nikolay N; Bobylev, Alexander G; Ulanova, Anna D; Kukushkin, Nikolay I; Podlubnaya, Zoya A; Vikhlyantsev, Ivan M

2017-10-01

Proteolysis can proceed via several distinct pathways such as the lysosomal, calcium-dependent, and ubiquitin-proteasome-dependent pathways. Calpains are the main proteases that cleave a large variety of proteins, including the giant sarcomeric proteins, titin and nebulin. Chronic ethanol feeding for 6 weeks did not affect the activities of μ-calpain and m-calpain in the m. gastrocnemius. In our research, changes in μ-calpain activity were studied in the m. gastrocnemius and m. soleus of chronically alcohol-fed rats after 6 months of alcohol intake. SDS-PAGE analysis was applied to detect changes in titin and nebulin contents. Titin phosphorylation analysis was performed using the fluorescent dye Pro-Q Diamond. Western blotting was used to determine μ-calpain autolysis as well as μ-calpain and calpastatin contents. The titin and nebulin mRNA levels were assessed by real-time PCR. The amounts of the autolysed isoform (78 kDa) of full-length μ-calpain (80 kDa) increased in the m. gastrocnemius and m. soleus of alcohol-fed rats. The calpastatin content increased in m. gastrocnemius. Decreased intact titin-1 (T1) and increased T2-proteolytic fragment contents were found in the m. gastrocnemius and m. soleus of the alcohol-fed rats. The nebulin content decreased in the rat gastrocnemius muscle of the alcohol-fed group. The phosphorylation levels of T1 and T2 were increased in the m. gastrocnemius and m. soleus, and decreased titin and nebulin mRNA levels were observed in the m. gastrocnemius. The nebulin mRNA level was increased in the soleus muscle of the alcohol-fed rats. In summary, our data suggest that prolonged chronic alcohol consumption for 6 months resulted in increased autolysis of μ-calpain in rat skeletal muscles. These changes were accompanied by reduced titin and nebulin contents, titin hyperphosphorylation, and development of hindlimb muscle atrophy in the alcohol-fed rats. Copyright © 2017 by the Research Society on Alcoholism.

Denervation-induced homeostatic dendritic plasticity in morphological granule cell models

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Hermann Cuntz

2014-03-01

Full Text Available Neuronal death and subsequent denervation of target areas are major consequences of several neurological conditions such asischemia or neurodegeneration (Alzheimer's disease. The denervation-induced axonal loss results in reorganization of the dendritic tree of denervated neurons. The dendritic reorganization has been previously studied using entorhinal cortex lesion (ECL. ECL leads to shortening and loss of dendritic segments in the denervated outer molecular layer of the dentate gyrus. However, the functional importance of these long-term dendritic alterations is not yet understood and their impact on neuronal electrical properties remains unclear. Here we analyzed what happens to the electrotonic structure and excitability of dentate granule cells after lesion-induced alterations of their dendritic morphology, assuming all other parameters remain equal. We performed comparative electrotonic analysis in anatomically and biophysically realistic compartmental models of 3D-reconstructed healthy and denervated granule cells. Using the method of morphological modeling based on optimization principles minimizing the amount of wiring and maximizing synaptic democracy, we built artificial granule cells which replicate morphological features of their real counterparts. Our results show that somatofugal and somatopetal voltage attenuation in the passive cable model are strongly reduced in denervated granule cells. In line with these predictions, the attenuation both of simulated backpropagating action potentials and forward propagating EPSPs was significantly reduced in dendrites of denervated neurons. Intriguingly, the enhancement of action potential backpropagation occurred specifically in the denervated dendritic layers. Furthermore, simulations of synaptic f-I curves revealed a homeostatic increase of excitability in denervated granule cells. In summary, our morphological and compartmental modeling indicates that unless modified by changes of

Measuring anisotropic muscle stiffness properties using elastography.

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Green, M A; Geng, G; Qin, E; Sinkus, R; Gandevia, S C; Bilston, L E

2013-11-01

Physiological and pathological changes to the anisotropic mechanical properties of skeletal muscle are still largely unknown, with only a few studies quantifying changes in vivo. This study used the noninvasive MR elastography (MRE) technique, in combination with diffusion tensor imaging (DTI), to measure shear modulus anisotropy in the human skeletal muscle in the lower leg. Shear modulus measurements parallel and perpendicular to the fibre direction were made in 10 healthy subjects in the medial gastrocnemius, soleus and tibialis anterior muscles. The results showed significant differences in the medial gastrocnemius (μ‖ = 0.86 ± 0.15 kPa; μ⊥ = 0.66 ± 0.19 kPa, P < 0.001), soleus (μ‖ = 0.83 ± 0.22 kPa; μ⊥ = 0.65 ± 0.13 kPa, P < 0.001) and the tibialis anterior (μ‖ = 0.78 ± 0.24 kPa; μ⊥ = 0.66 ± 0.16 kPa, P = 0.03) muscles, where the shear modulus measured in the direction parallel is greater than that measured in the direction perpendicular to the muscle fibres. No significant differences were measured across muscle groups. This study provides the first direct estimates of the anisotropic shear modulus in the triceps surae muscle group, and shows that the technique may be useful for the probing of mechanical anisotropy changes caused by disease, aging and injury. Copyright © 2013 John Wiley & Sons, Ltd.

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

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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.

Effects of Heat Stress Treatment on Age-dependent Unfolded Protein Response in Different Types of Skeletal Muscle.

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Tamura, Yuki; Matsunaga, Yutaka; Kitaoka, Yu; Hatta, Hideo

2017-03-01

Mitochondrial and endoplasmic reticulum (ER) stress, and subsequently activated responses (mitochondrial/ER unfolded protein responses; UPRmt/UPRER), are involved in the pathogenesis of sarcopenia. To extend both basic and translational knowledge, we examined (i) whether age-induced mitochondrial and ER stress depend on skeletal muscle type in mice and (ii) whether heat stress treatment, a suggested strategy for sarcopenia, improves age-induced mitochondrial and ER stress. Aged (21-month-old) mice showed more severe mitochondrial stress and UPRmt than young (12-week-old) mice, based on increased oxidative stress, mitochondrial proteases, and mitochondrial E3 ubiquitin ligase. The aged mice also showed ER stress and UPRER, based on decreased ER enzymes and increased ER stress-related cell death. These changes were much more evident in soleus muscle than in gastrocnemius and plantaris muscles. After daily heat stress treatment (40 °C chamber for 30 minutes per day) for 4 weeks, mice showed remarkable improvements in age-related changes in soleus muscle. Heat stress had only minor effects in gastrocnemius and plantaris muscles. Based on these findings, age-associated mitochondrial stress, ER stress, and UPRmt/ER vary qualitatively with skeletal muscle type. Our results suggest a molecular basis for the beneficial effects of heat stress on muscle atrophy with age in soleus muscle. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Unicompartmental muscle edema: an early sign of deep venous thrombosis

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Liu, Patrick T. [Mayo Clinic Scottsdale, Department of Diagnostic Radiology, 13400 E. Shea Boulevard, Scottsdale, AZ 85259 (United States); Ilaslan, Hakan [Mayo Clinic Rochester, Department of Diagnostic Radiology, Rochester, Minnesota (United States)

2003-01-01

The finding of muscle edema restricted to a single muscle compartment on MRI usually indicates a diagnosis of traumatic injury, myositis, denervation or neoplasm. This case demonstrates that deep venous thrombosis can also be the cause of isolated deep posterior compartment muscle edema in the calf and should be considered in the differential diagnosis even in the absence of diffuse soft tissue or subcutaneous edema. (orig.)

High incidence of secondary hypertension in patients referred for renal denervation

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Olsen, Lene Kjær; Kamper, Anne-Lise; Svendsen, Jesper Hastrup

2014-01-01

. Thus, 91 patients were screened, and of those 51 were found to be candidates for renal denervation. Forty patients were not candidates, of which secondary hypertension was the most common cause (n = 10). Only 51% of patients referred for renal denervation were eligible for treatment. The prevalence...... of secondary hypertension was 10% of the referred population. Secondary hypertension should therefore be considered in the evaluation of candidates for renal denervation.......Percutaneous renal denervation is a new treatment option for patients with resistant hypertension and little is known about the eligibility of patients referred. 100 consecutive patients were referred for renal denervation from March 2011 through September 2012. Clinical data were prospectively...

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

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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.

Unilateral hypoplasia with contralateral hypertrophy of anterior belly of digastric muscle: a case report.

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Ochoa-Escudero, Martin; Juliano, Amy F

2016-10-01

Anomalies of the anterior belly of the digastric muscle (DM) are uncommon. We present a case of hypoplasia of the anterior belly of the left DM with hypertrophy of the anterior belly of the contralateral DM. The importance of recognizing this finding is to differentiate hypoplasia of the anterior belly of the DM from denervation atrophy, and not to confuse contralateral hypertrophy with a submental mass or lymphadenopathy. In denervation atrophy of the anterior belly of the DM, associated atrophy of the ipsilateral mylohyoid muscle is present. Hypertrophy of the anterior belly of the contralateral DM can be differentiated from a submental mass or lymphadenopathy by recognizing its isodensity on computed tomography and isointensity on magnetic resonance imaging to other muscles, without abnormal contrast enhancement.

Effects of treadmill training on the arteriolar and venular portions of capillary in soleus muscle of young and middle-aged rats.

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Suzuki, J; Gao, M; Batra, S; Koyama, T

1997-02-01

The effects of a 6-week programme of endurance training on soleus muscle capillarity were examined, in terms particularly of the proportions of arteriolar and venular capillaries and their capillary domain area, in young (3-week-old) and middle-aged (54-week-old) Wistar rats. Exercise protocols for the young training group were: 10-22.5 m min-1 60 min day-1 for 6 days a week, with a gradient of 7 degrees during the final 2 weeks; for the middle-aged training group, the protocols were: 10-20 m min-1. 50 min day-1 for 6 days a week. In both young and middle-aged training groups, the density of arteriolar capillaries was significantly increased (P demand. In both young and middle-aged rats, capillary domain area and Krogh's tissue cylinder radii in all capillary portions decreased after training. These results suggest that adaptive changes in oxygen transport system, identified as an increase in the arteriolar capillary and a reduction in diffusion distance for oxygen, were observed in middle-aged as well as in young rats. However, capillary angiogenesis induced by exercise appeared to be greater in young than in middle-aged rats.

Time course of myosin heavy chain transitions in neonatal rats: importance of innervation and thyroid state

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Adams, G. R.; McCue, S. A.; Zeng, M.; Baldwin, K. M.

1999-01-01

During the postnatal period, rat limb muscles adapt to weight bearing via the replacement of embryonic (Emb) and neonatal (Neo) myosin heavy chains (MHCs) by the adult isoforms. Our aim was to characterize this transition in terms of the six MHC isoforms expressed in skeletal muscle and to determine the importance of innervation and thyroid hormone status on the attainment of the adult MHC phenotype. Neonatal rats were made hypothyroid via propylthiouracil (PTU) injection. In normal and PTU subgroups, leg muscles were unilaterally denervated at 15 days of age. The MHC profiles of plantaris (PLN) and soleus (Sol) muscles were determined at 7, 14, 23, and 30 days postpartum. At day 7, the Sol MHC profile was 55% type I, 30% Emb, and 10% Neo; in the PLN, the pattern was 60% Neo and 25% Emb. By day 30 the Sol and PLN had essentially attained an adult MHC profile in the controls. PTU augmented slow MHC expression in the Sol, whereas in the PLN it markedly repressed IIb MHC by retaining neonatal MHC expression. Denervation blunted the upregulation of IIb in the PLN and of Type I in the Sol and shifted the pattern to greater expression of IIa and IIx MHCs in both muscles. In contrast to previous observations, these findings collectively suggest that both an intact thyroid and innervation state are obligatory for the attainment of the adult MHC phenotype, particularly in fast-twitch muscles.

The mRNA expression profile of metabolic genes relative to MHC isoform pattern in human skeletal muscles

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Plomgaard, Peter; Penkowa, Milena; Leick, Lotte

2006-01-01

The metabolic profile of rodent muscle is generally reflected in the myosin heavy chain (MHC) fiber-type composition. The present study was conducted to test the hypothesis that metabolic gene expression is not tightly coupled with MHC fiber-type composition for all genes in human skeletal muscle....... Triceps brachii, vastus lateralis quadriceps, and soleus muscle biopsies were obtained from normally physically active, healthy, young male volunteers, because these muscles are characterized by different fiber-type compositions. As expected, citrate synthase and 3-hydroxyacyl dehydrogenase activity...... of a broad range of metabolic genes. The triceps muscle had two- to fivefold higher MHC IIa, phosphofructokinase, and LDH A mRNA content and two- to fourfold lower MHC I, lipoprotein lipase, CD36, hormone-sensitive lipase, and LDH B and hexokinase II mRNA than vastus lateralis or soleus. Interestingly...

Alpha-adrenergic receptors in rat skeletal muscle

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Rattigan, S; Appleby, G J; Edwards, S J

1986-01-01

Sarcolemma-enriched preparations from muscles rich in slow oxidative red fibres contained specific binding sites for the alpha 1 antagonist, prazosin (e.g. soleus Kd 0.13 nM, Bmax 29 fmol/mg protein). Binding sites for prazosin were almost absent from white muscle. Displacement of prazosin bindin...... adrenergic receptors are present on the sarcolemma of slow oxidative red fibres of rat skeletal muscle. The presence provides the mechanistic basis for apparent alpha-adrenergic effects to increase glucose and oxygen uptake in perfused rat hindquarter....

Afferent Innervation, Muscle Spindles, and Contractures Following Neonatal Brachial Plexus Injury in a Mouse Model.

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Nikolaou, Sia; Hu, Liangjun; Cornwall, Roger

2015-10-01

We used an established mouse model of elbow flexion contracture after neonatal brachial plexus injury (NBPI) to test the hypothesis that preservation of afferent innervation protects against contractures and is associated with preservation of muscle spindles and ErbB signaling. A model of preganglionic C5 through C7 NBPI was first tested in mice with fluorescent axons using confocal imaging to confirm preserved afferent innervation of spindles despite motor end plate denervation. Preganglionic and postganglionic injuries were then created in wild-type mice. Four weeks later, we assessed total and afferent denervation of the elbow flexors by musculocutaneous nerve immunohistochemistry. Biceps muscle volume and cross-sectional area were measured by micro computed tomography. An observer who was blinded to the study protocol measured elbow flexion contractures. Biceps spindle and muscle fiber morphology and ErbB signaling pathway activity were assessed histologically and immunohistochemically. Preganglionic and postganglionic injuries caused similar total denervation and biceps muscle atrophy. However, after preganglionic injuries, afferent innervation was partially preserved and elbow flexion contractures were significantly less severe. Spindles degenerated after postganglionic injury but were preserved after preganglionic injury. ErbB signaling was inactivated in denervated spindles after postganglionic injury but ErbB signaling activity was preserved in spindles after preganglionic injury with retained afferent innervation. Preganglionic and postganglionic injuries were associated with upregulation of ErbB signaling in extrafusal muscle fibers. Contractures after NBPI are associated with muscle spindle degeneration and loss of spindle ErbB signaling activity. Preservation of afferent innervation maintained spindle development and ErbB signaling activity, and protected against contractures. Pharmacologic modulation of ErbB signaling, which is being investigated as a

Hydrogen peroxide modulates Ca2+-activation of single permeabilized fibres from fast- and slow-twitch skeletal muscles of rats.

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Plant, D R; Lynch, G S; Williams, D A

2000-01-01

We examined the effects of redox modulation on single membrane-permeabilized fibre segments from the fast-twitch extensor digitorum longus (EDL) and slow-twitch soleus muscles of adult rats to determine whether the contractile apparatus was the redox target responsible for the increased contractility of muscles exposed to low concentrations of H2O2. The effects of H2O2 on maximum Ca2+-activated force were dose-dependent with 30 min exposure to 5 mM H2O2 causing a progressive decrease by 22+/-3 and 13+/-2% in soleus and EDL permeabilized muscle fibres, respectively. Lower concentrations of exogenous H2O2 (100 microM and 1 mM) had no effect on maximum Ca2+-activated force. Subsequent exposure to the reductant dithiothreitol (DTT, 10 mM, 10 min) fully reversed the H2O2-induced depression of force in EDL, but not in soleus muscle fibres. Incubation with DTT alone for 10 min did not alter Ca2+-activated force in either soleus or EDL muscle fibres. The sensitivity of the contractile filaments to Ca2+ (pCa50) was not altered by exposure to any concentration of exogenous H2O2. However, all concentrations of H2O2 diminished the Hill coefficient in permeabilized fibres from the EDL muscle, indicating that the cooperativity of Ca2+ binding to troponin is altered. H2O2 (5 mM) did not affect rigor force, which indicates that the number of crossbridges participating in contraction was not reduced. In conclusion, H2O2 may reduce the maximum Ca2+ activated force production in skinned muscle fibres by decreasing the force per crossbridge.

Accumulation of silver from drinking water into cerebellum and musculus soleus in mice

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Pelkonen, Kai H.O.; Heinonen-Tanski, Helvi; Haenninen, Osmo O.P.

2003-01-01

In spite of the general toxicity, ecotoxicity and sparsely known metabolism of silver, WHO allows silver ions (Ag) up to 0.1 mg/l in drinking water disinfection. In order to determine the accumulation and distribution of silver in a mammalian body, mice were given for 1 and 2 weeks drinking water containing a 3-fold lower concentration, namely 0.03 mg/l silver ions as silver nitrate labelled with 110m Ag. The silver concentrations in different tissues were analysed by gamma radioactivity. The saturation of tissues with silver seems to occur quickly, as there were no statistical differences between silver contents of mice tissues in spite of the study design that mice were administered silver for 1 or 2 weeks. The highest concentrations were found in musculus soleus (m. soleus), cerebellum, spleen, duodenum, and myocardial muscle in the rank order. Concentrations of silver in musculus gastrocnemius (m. gastrocnemius) were found to correlate negatively with cerebrum and positively with blood and kidneys. The accumulation of silver into organs and tissues important in motor functions may be of relevance especially in emergency and catastrophe situations in which accurate motor functions may be critical. A re-evaluation of the present recommendations on the use of silver salts for disinfection of drinking water might be necessary

Membrane proteins involved in potassium shifts during muscle activity and fatigue

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Kristensen, Michael; Hansen, T.; Juel, C.

2006-01-01

while trying to manipulate the opening probability or transport capacity of these proteins during electrical stimulation of isolated soleus muscles. All experiments were made with excised muscle from male Wistar rats. Kir2.1 channels were almost undetectable in the sarcolemmal membrane but present...... muscle contractions, whereas Kir2.1 and NKCC1 may have a role in K+ reuptake. channels and cotransporters; T tubule...

Coordinate Transcriptomic and Metabolomic Effects of the Insulin Sensitizer Rosiglitazone on Fundamental Metabolic Pathways in Liver, Soleus Muscle, and Adipose Tissue in Diabetic db/db Mice

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Sabrina Le Bouter

2010-01-01

Full Text Available Rosiglitazone (RSG, developed for the treatment of type 2 diabetes mellitus, is known to have potent effects on carbohydrate and lipid metabolism leading to the improvement of insulin sensitivity in target tissues. To further assess the capacity of RSG to normalize gene expression in insulin-sensitive tissues, we compared groups of 18-day-treated db/db mice with increasing oral doses of RSG (10, 30, and 100 mg/kg/d with untreated non-diabetic littermates (db/+. For this aim, transcriptional changes were measured in liver, inguinal adipose tissue (IAT and soleus muscle using microarrays and real-time PCR. In parallel, targeted metabolomic assessment of lipids (triglycerides (TGs and free fatty acids (FFAs in plasma and tissues was performed by UPLC-MS methods. Multivariate analyses revealed a relationship between the differential gene expressions in liver and liver trioleate content and between blood glucose levels and a combination of differentially expressed genes measured in liver, IAT, and muscle. In summary, we have integrated gene expression and targeted metabolomic data to present a comprehensive overview of RSG-induced changes in a diabetes mouse model and improved the molecular understanding of how RSG ameliorates diabetes through its effect on the major insulin-sensitive tissues.

Ultrastructural muscle and neuro-muscular junction alterations in polymyositis

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L. L. Babakova

2012-01-01

Full Text Available Ultrastructural analysis of 7 biopsies from m.palmaris longus and m.deltoideus in patients with confirmed polymyositis revealed alterationand degeneration of muscle fibers and anomalies of neuro-muscular junction (NMJ. The NMJ abnormalities and following denervation ofmuscle fibers in polymyositis start with subsynaptic damages. The occurance of regeneration features in muscle fibers at any stage is characteristic for PM.

Skeletal muscle myostatin mRNA expression is fiber-type specific and increases during hindlimb unloading

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Carlson, C. J.; Booth, F. W.; Gordon, S. E.

1999-01-01

Transgenic mice lacking a functional myostatin (MSTN) gene demonstrate greater skeletal muscle mass resulting from muscle fiber hypertrophy and hyperplasia (McPherron, A. C., A. M. Lawler, and S. -J. Lee. Nature 387: 83-90, 1997). Therefore, we hypothesized that, in normal mice, MSTN may act as a negative regulator of muscle mass. Specifically, we hypothesized that the predominately slow (type I) soleus muscle, which demonstrates greater atrophy than the fast (type II) gastrocnemius-plantaris complex (Gast/PLT), would show more elevation in MSTN mRNA abundance during hindlimb unloading (HU). Surprisingly, MSTN mRNA was not detectable in weight-bearing or HU soleus muscle, which atrophied 42% by the 7th day of HU in female ICR mice. In contrast, MSTN mRNA was present in weight-bearing Gast/PLT muscle and was significantly elevated (67%) at 1 day but not at 3 or 7 days of HU. However, the Gast/PLT muscle had only atrophied 17% by the 7th day of HU. Because the soleus is composed only of type I and IIa fibers, whereas the Gast/PLT expresses type IId/x and IIb in addition to type I and IIa, it was necessary to perform a more careful analysis of the relationship between MSTN mRNA levels and myosin heavy-chain (MHC) isoform expression (as a marker of fiber type). A significant correlation (r = 0.725, P < 0. 0005) was noted between the percentage of MHC isoform IIb expression and MSTN mRNA abundance in several muscles of the mouse hindlimb. These results indicate that MSTN expression is not strongly associated with muscle atrophy induced by HU; however, it is strongly associated with MHC isoform IIb expression in normal muscle.

Interaction of Mechanical Load with Growth Hormone (GH) and Insulin-Like Growth Factor I (IGF-I) on Slow-Twitch Skeletal Muscle and Bone

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Linderman, Jon K.; Gosselink, Kristin L.; Wang, Tommy J.; Mukku, Venkat R.; Grindeland, Richard E.

1994-01-01

Exogenous humoral growth factors, combined with increased mechanical loading, reportedly induce hypertrophy of fast-, but not slow-twitch skeletal muscles, and have little effect in attenuating atrophy of slow-twitch muscle associated with exposure to microgravity in animals with intact neuroendocrine systems. These observations suggest that anabolic adjuvants and muscle tension do not interact to stimulate growth or maintenance of slow-twitch skeletal muscle. The purpose of the present study was to determine whether a chronic increase in mechanical loading (synergistic ablation) or hindlimb unweighting (hindlimb suspension) interact with exogenous GH and IGF-I (Genentech, So San Francisco, CA) in the slow-twitch soleus muscles of female rats (approx. 250 g). Bilateral ablation of the plantaris and gastrocnemius muscles induced 38% and 40% increases in the absolute (mg/pair) and relative (mg/100 g body weight) weights of the soleus, respectively (p less than or = 0.05), in ambulatory rats. GH and IGF-I interacted with chronic loading to increase absolute soleus mass an additional 20% (p less than or = 0.05), and mixed and myofibrillar protein contents an additional 12% and 7%, respectively (NS). In contrast, hindlimb suspension (HLS) resulted in 20% and 18% decreases in the absolute and relative weights of the soleus, respectively (p less than or = 0.05); GH and IGF-I did not spare loss of soleus mass or protein content in HLS rats. HLS decreased tibial plate thickness approx. 11% (p less than or = 0.05), but not weights of the tibia or femus. GH and IGF-I increased tibial plate thickness approx. 30% (p less than or = 0.05), in ambulatory and HLS rats, and increased femur and tibial weights 12% (p less than or = 0.05) and 8% (NS), respectively, in ambulatory rats, but had no effect in HLS rats. Results of the present investigation suggest that GH and IGF-I can stimulate hypertrophy of slow-twitch skeletal muscle when chronically overloaded, but can also stimulate

[Expert consensus statement on interventional renal sympathetic denervation for hypertension treatment].

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Mahfoud, F; Vonend, O; Bruck, H; Clasen, W; Eckert, S; Frye, B; Haller, H; Hausberg, M; Hoppe, U C; Hoyer, J; Hahn, K; Keller, T; Krämer, B K; Kreutz, R; Potthoff, S A; Reinecke, H; Schmieder, R; Schwenger, V; Kintscher, U; Böhm, M; Rump, L C

2011-11-01

This commentary summarizes the expert consensus and recommendations of the working group 'Herz und Niere' of the German Society of Cardiology (DGK), the German Society of Nephrology (DGfN) and the German Hypertension League (DHL) on renal denervation for antihypertensive treatment. Renal denervation is a new, interventional approach to selectively denervate renal afferent and efferent sympathetic fibers. Renal denervation has been demonstrated to reduce office systolic and diastolic blood pressure in patients with resistant hypertension, defined as systolic office blood pressure ≥ 160 mm Hg and ≥ 150 mm Hg in patients with diabetes type 2, which should currently be used as blood pressure thresholds for undergoing the procedure. Exclusion of secondary hypertension causes and optimized antihypertensive drug treatment is mandatory in every patient with resistant hypertension. In order to exclude pseudoresistance, 24-hour blood pressure measurements should be performed. Preserved renal function was an inclusion criterion in the Symplicity studies, therefore, renal denervation should be only considered in patients with a glomerular filtration rate > 45 ml/min. Adequate centre qualification in both, treatment of hypertension and interventional expertise are essential to ensure correct patient selection and procedural safety. Long-term follow-up after renal denervation and participation in the German Renal Denervation (GREAT) Registry are recommended to assess safety and efficacy after renal denervation over time. © Georg Thieme Verlag KG Stuttgart · New York.

Renin angiotensin system and cardiac hypertrophy after sinoaortic denervation in rats

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Aline Cristina Piratello

2010-01-01

Full Text Available OBJECTIVE: The aim of this study was to evaluate the role of angiotensin I, II and 1-7 on left ventricular hypertrophy of Wistar and spontaneously hypertensive rats submitted to sinoaortic denervation. METHODS: Ten weeks after sinoaortic denervation, hemodynamic and morphofunctional parameters were analyzed, and the left ventricle was dissected for biochemical analyses. RESULTS: Hypertensive groups (controls and denervated showed an increase on mean blood pressure compared with normotensive ones (controls and denervated. Blood pressure variability was higher in denervated groups than in their respective controls. Left ventricular mass and collagen content were increased in the normotensive denervated and in both spontaneously hypertensive groups compared with Wistar controls. Both hypertensive groups presented a higher concentration of angiotensin II than Wistar controls, whereas angiotensin 1-7 concentration was decreased in the hypertensive denervated group in relation to the Wistar groups. There was no difference in angiotensin I concentration among groups. CONCLUSION: Our results suggest that not only blood pressure variability and reduced baroreflex sensitivity but also elevated levels of angiotensin II and a reduced concentration of angiotensin 1-7 may contribute to the development of left ventricular hypertrophy. These data indicate that baroreflex dysfunction associated with changes in the renin angiotensin system may be predictive factors of left ventricular hypertrophy and cardiac failure.

Soleus stretch reflex during cycling

DEFF Research Database (Denmark)

Grey, Michael James; Pierce, C. W.; Milner, T. E.

2001-01-01

The modulation and strength of the human soleus short latency stretch reflex was investigated by mechanically perturbing the ankle during an unconstrained pedaling task. Eight subjects pedaled at 60 rpm against a preload of 10 Nm. A torque pulse was applied to the crank at various positions durin...

Follistatin: A Potential Anabolic Treatment for Re-Innervated Muscle

Science.gov (United States)

2017-09-01

Observations: ELISA , muscle histology, nerve histology, etc.are pending and no final conclusions can be made. 1. 3-month Protein: a. Muscle Weight: No...and virus needed for the study and also helped in Pilot Study- ELISA . He presented the following abstract in VCU School of Medicine Student Research...denervation groups (1-6): ▪ Follistatin ELISA – Run the assay, collect data, and prepare to present data ▪ Muscle Histology – Process tissue, image the

Prolonging the duration of masseter muscle reduction by adjusting the masticatory movements after the treatment of masseter muscle hypertrophy with botulinum toxin type a injection.

Science.gov (United States)

Wei, Jiao; Xu, Hua; Dong, Jiasheng; Li, Qingfeng; Dai, Chuanchang

2015-01-01

Botulinum toxin type A (BTX-A) is widely used for the clinical treatment of masseteric hypertrophy. Until now, few reports have discussed how to prolong the duration of its effectiveness. This study evaluated that purposely adjusting the masticatory movements is possible of postponing the masseter muscle rehypertrophy. Ninety-eight patients were randomly and equally divided into 2 groups, and 35 U BTX-A per side was injected into the masseters. The thickness and volume of the masticatory muscles were measured by ultrasound and computerized tomography, respectively. Patients in Group 1 were instructed to strengthen their masticatory effort during the denervated atrophic stage of the masseter (the interval was evaluated by real-time ultrasound monitoring), whereas patients in Group 2 were not given this instruction. When the masseter muscle began to recover, patients in both groups were instructed to reduce their chewing. The duration of the masseter muscle rehypertrophy was significantly prolonged in Group 1 patients. The thickness and the volume of the other masticatory muscles were significantly increased in Group 1 but were either slightly decreased or insignificantly different in Group 2. Purposely strengthening masticatory muscle movement during the denervated atrophic stage of the masseter can prolong the duration of masseter rehypertrophy.

Pseudohypertrophy of the calf muscles in a patient with diabetic neuropathy: a case report

International Nuclear Information System (INIS)

Lee, Eun Jin; Lee, Young Hwan; Jung, Kyung Jae; Park, Young Chan; Kim, Ho Kyun; Kim, Ok Dong

2007-01-01

Partial or complete loss of innervation of skeletal muscle leads to muscle weakness and atrophic changes, resulting in decreased muscle volume with fatty replacement. Rarely, enlargement of the affected muscle may occur, related to two processes: true hypertrophy and pseudohypertrophy. We report CT and MR findings of the pseudohypertrophy of calf muscles, especially the soleus and gastrocnemius muscles, in a patient with diabetic neuropathy that showed increased muscle volume with diffuse fatty replacement and the presence of scanty muscle fibers

Pseudohypertrophy of the calf muscles in a patient with diabetic neuropathy: a case report

Energy Technology Data Exchange (ETDEWEB)

Lee, Eun Jin; Lee, Young Hwan; Jung, Kyung Jae; Park, Young Chan; Kim, Ho Kyun; Kim, Ok Dong [School of Medicine, Catholic University of Daegu, Daegu (Korea, Republic of)

2007-09-15

Partial or complete loss of innervation of skeletal muscle leads to muscle weakness and atrophic changes, resulting in decreased muscle volume with fatty replacement. Rarely, enlargement of the affected muscle may occur, related to two processes: true hypertrophy and pseudohypertrophy. We report CT and MR findings of the pseudohypertrophy of calf muscles, especially the soleus and gastrocnemius muscles, in a patient with diabetic neuropathy that showed increased muscle volume with diffuse fatty replacement and the presence of scanty muscle fibers.

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 ...

Quantitative analysis of immune cell subset infiltration of supraspinatus muscle after severe rotator cuff injury.

Science.gov (United States)

Krieger, J R; Tellier, L E; Ollukaren, M T; Temenoff, J S; Botchwey, E A

2017-06-01

Rotator cuff tears cause muscle degeneration that is characterized by myofiber atrophy, fatty infiltration, and fibrosis and is minimally responsive to current treatment options. The underlying pathogenesis of rotator cuff muscle degeneration remains to be elucidated, and increasing evidence implicates immune cell infiltration as a significant factor. Because immune cells are comprised of highly heterogeneous subpopulations that exert divergent effects on injured tissue, understanding trafficking and accumulation of immune subpopulations may hold the key to more effective therapies. The present study quantifies subpopulations of immune cells infiltrating the murine supraspinatus muscle after severe rotator cuff injury that includes tenotomy and denervation. Rotator cuff injury stimulates dramatic infiltration of mononuclear phagocytes, enriches mononuclear phagocytes in non-classical subpopulations, and enriches T lymphocytes in T H and T reg subpopulations. The combination of tenotomy plus denervation significantly increases mononuclear phagocyte infiltration, enriches macrophages in the non-classical subpopulation, and decreases T lymphocyte enrichment in T H cells compared to tenotomy alone. Depletion of circulating monocytes via liposomal clodronate accelerates supraspinatus atrophy after tenotomy and denervation. The study may aid rational design of immunologically smart therapies that harness immune cells to enhance outcomes after rotator cuff tears.

Corticospinal excitability of the ankle extensor muscles is enhanced in ballet dancers.

Science.gov (United States)

Saito, Sakiko; Obata, Hiroki; Endoh, Takashi; Kuno-Mizumura, Mayumi; Nakazawa, Kimitaka

2014-09-01

We tested the corticospinal excitability of the soleus muscle in ballet dancers to clarify whether the presumed long-term repetition of the specific plantarflexion results in changes of excitability in this neural pathway. We compared motor evoked potentials of the soleus muscle at rest and during isometric contraction of the plantar flexors in dancers and non-dancers. The amplitudes of motor evoked potentials elicited by transcranial magnetic stimulation during contraction were examined against the background electromyographic activity. A regression line was calculated for each subject. Results showed that the slope of the regression line is significantly greater in the dancer group than in the control group, suggesting that the corticospinal tract of ballet dancers has adapted to long-term repetition of plantarflexion in daily ballet training.

Effects of acute exposure of heavy ion to spinal cord on the properties of motoneurons and muscle fibers in rats (the 3rd report)

International Nuclear Information System (INIS)

Ishihara, Akihiko; Ohira, Yoshinobu; Kawano, Fuminori; Wang, Xiao Dong; Nagaoka, Shunji; Nojima, Kumie

2005-01-01

The effects of acute exposure of heavy ion on the properties of spinal motoneurons and their innervating muscle fibers were investigated. A 15, 20, 40, 50, or 70 Gy dose of heavy ion was applied to the lumbar 4th to 6th segments of the spinal cord in 8-week-old male rats. Both the control and heavy-ion-exposed rats were sacrificed one month after exposure to heavy ion. The number, cell body size, and oxidative enzyme activity of spinal motoneurons innervating the soleus and plantaris muscles were analyzed by a computer-assisted image processing system. In addition, cell size, oxidative enzyme activity, and expression of myosin heavy chain isoforms in the soleus and plantaris muscles were analyzed. There were no differences in the number of spinal motoneurons innervating the soleus and plantaris muscles between the control and heavy-ion-exposed rats, irrespective of the dose level. On the other hand, cell body sizes were decreased and oxidative enzyme activities were disappeared in spinal motoneurons of the heavy-ion-exposed rats at the dose levels of 40, 50, and 70 Gy. There were no differences in the cell size, oxidative enzyme activity, or expression of myosin heavy chain isoforms of the soleus and plantaris muscles between the control and heavy-ion-exposed rats, irrespective of the dose level. It is concluded that more than 40 Gy dose of heavy ion affects the properties of spinal motoneurons, although there are no influences on the properties of muscle fibers which they innervate. (author)

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.

Effect of tibial bone resection on the development of fast- and slow-twitch skeletal muscles in foetal sheep.

Science.gov (United States)

West, J M; Williams, N A; Luff, A R; Walker, D W

2000-04-01

To determine if longitudinal bone growth affects the differentiation of fast- and slow-twitch muscles, the tibial bone was sectioned at 90 days gestation in foetal sheep so that the lower leg was permanently without structural support. At 140 days (term is approximately 147 days) the contractile properties of whole muscles, activation profiles of single fibres and ultrastructure of fast- and slow-twitch muscles from the hindlimbs were studied. The contractile and activation profiles of the slow-twitch soleus muscles were significantly affected by tibial bone resection (TIBX). The soleus muscles from the TIBX hindlimbs showed: (1) a decrease in the time to peak of the twitch responses from 106.2 +/- 10.7 ms (control, n = 4) to 65.1 +/- 2.48 ms (TIBX, n = 5); (2) fatigue profiles more characteristic of those observed in the fast-twitch muscles: and (3) Ca2+ - and Sr2+ -activation profiles of skinned fibres similar to those from intact hindlimbs at earlier stages of gestation. In the FDL, TIBX did not significantly change whole muscle twitch contraction time, the fatigue profile or the Ca2+ - and Sr2+ -activation profiles of skinned fibres. Electron microscopy showed an increased deposition of glycogen in both soleus and FDL muscles. This study shows that the development of the slow-twitch phenotype is impeded in the absence of the physical support normally provided by the tibial bone. We suggest that longitudinal stretch is an important factor in allowing full expression of the slow-twitch phenotype.

Upper motor neurone modulation of the structure of the terminal cisternae in rat skeletal muscle fibres.

Science.gov (United States)

Dulhunty, A F; Gage, P W; Valois, A A

1981-12-23

There are fewer indentations on the flat surfaces of terminal cisternae in soleus (slow-twitch) than in extensor digitorum longus (EDL, fast-twitch) muscle fibres of rats. Following mid-thoracic spinal cord transection, there is an increase in the number of indentations in soleus fibres but no change in EDL fibres. The increase in the numbers of indentations after spinal cord transections is correlated with changes in the contractile and charge movement properties of the soleus fibres so that they resemble normal EDL fibres. The indentations appear to have an important role in excitation-contraction coupling.

Multiple signalling pathways redundantly control glucose transporter GLUT4 gene transcription in skeletal muscle

DEFF Research Database (Denmark)

Murgia, Marta; Elbenhardt Jensen, Thomas; Cusinato, Marzia

2009-01-01

on pharmacological evidence. Here, we have used a more specific genetic approach to establish the relative role of the three pathways in fast and slow muscles. Plasmids coding for protein inhibitors of CaMKII or calcineurin were co-transfected in vivo with a GLUT4 enhancer-reporter construct either in normal mice...... or in mice expressing a dominant negative AMPK mutant. GLUT4 reporter activity was not inhibited in the slow soleus muscle by blocking either CaMKII or calcineurin alone, but was inhibited by blocking both pathways. GLUT4 reporter activity was likewise unchanged in the soleus of dnAMPK mice......, but was significantly reduce by incapacitation of either CaMKII or calcineurin in these mice. On the other hand, in the fast tibialis anterior muscle, calcineurin appears to exert a prominent role in the control of GLUT4 reporter activity, independent of CaMKII and AMPK. The results point to a muscle type...

Renal sympathetic denervation: MDCT evaluation of the renal arteries.

LENUS (Irish Health Repository)

Hutchinson, Barry D

2013-08-01

Percutaneous transluminal renal sympathetic denervation is a new treatment of refractory systemic hypertension. The purpose of this study was to assess the clinical utility of MDCT to evaluate the anatomic configuration of the renal arteries in the context of renal sympathetic denervation.

Decrease of Na, K-ATPase Electrogenic Contribution and Resting Membrane Potential of Rat Soleus after 3 Days of Hindlimb Unloading

Science.gov (United States)

Krivoi, I. I.; Kravtsova, V. V.; Drabkina, T. M.; Prokofiev, A. V.; Nikolsky, E. E.; Shenkman, B. S.

2008-06-01

The Na,K-ATPase activity is critically important for excitability, electrogenesis and contractility of skeletal muscle expressing ? and ? isoforms of the enzyme [6, 9]. It is well known that disuse induced by hindlimb unloading (HU) leads to progressive atrophy of skeletal muscle; the muscle undergoes a number of dramatic remodeling events. In particular, changes in ion channel expression in response to muscle unweighting were observed [1, 8]. Decrease of resting membrane potential (RMP), electrogenic contribution of Na,K-ATPase and membrane resistance during 7-28 days of HU was shown [8, 10]. The intrinsic mechanisms involved in the process have not been revealed until present. At the same time, the understanding of these mechanisms could be crucial for the disclosing the mechanisms underlying the resting Ca2+ accumulation in the cytoplasm of the unloaded muscle [3, 7]. In the present study, the effect of early (3 days) HU-induced disuse of slow-twitch soleus muscle on membrane electrogenesis as well as on electrogenic contribution of Na,K-ATPase isoforms was investigated.

Intrapericardial Denervation: Responses to Water Immersion in Rhesus Monkeys

Science.gov (United States)

McKeever, Kenneth H.; Keil, Lanny C.; Sandler, Harold

1995-01-01

Eleven anesthetized rhesus monkeys were used to study cardiovascular, renal, and endocrine alterations associated with 120 min of head-out water immersion. Five animals underwent complete intrapericardial denervation using the Randall technique, while the remaining six monkeys served as intact controls. Each animal was chronically instrumented with an electromagnetic flow probe on the ascending aorta, a strain gauge pressure transducer implanted in the apex of the left ventricle (LV), and electrocardiogram leads anchored to the chest wall and LV. During immersion, LV end-diastolic pressure, urine flow, glomerular filtration rate, sodium excretion, and circulating atrial natriuretic peptide (ANP) each increased (P less than 0.05) for intact and denervated monkeys. There were no alterations in free water clearance in either group during immersion, yet fractional excretion of free water increased (P less than 0.05) in the intact monkeys. Plasma renin activity (PRA) decreased (P less than 0.05) during immersion in intact monkeys but not the denervated animals. Plasma vasopressin (PVP) concentration decreased (P less than 0.05) during the first 30 min of immersion in both groups but was not distinguishable from control by 60 min of immersion in denervated monkeys. These data demonstrate that complete cardiac denervation does not block the rise in plasma ANP or prevent the natriuresis associated with head-out water immersion. The suppression of PVP during the first minutes of immersion after complete cardiac denervation suggests that extracardiac sensing mechanisms associated with the induced fluid shifts may be responsible for the findings.

Muscle Expression of SOD1G93A Triggers the Dismantlement of Neuromuscular Junction via PKC-Theta.

Science.gov (United States)

Dobrowolny, Gabriella; Martini, Martina; Scicchitano, Bianca Maria; Romanello, Vanina; Boncompagni, Simona; Nicoletti, Carmine; Pietrangelo, Laura; De Panfilis, Simone; Catizone, Angela; Bouchè, Marina; Sandri, Marco; Rudolf, Rüdiger; Protasi, Feliciano; Musarò, Antonio

2018-04-20

Neuromuscular junction (NMJ) represents the morphofunctional interface between muscle and nerve. Several chronic pathologies such as aging and neurodegenerative diseases, including muscular dystrophy and amyotrophic lateral sclerosis, display altered NMJ and functional denervation. However, the triggers and the molecular mechanisms underlying the dismantlement of NMJ remain unclear. Here we provide evidence that perturbation in redox signaling cascades, induced by muscle-specific accumulation of mutant SOD1 G93A in transgenic MLC/SOD1 G93A mice, is causally linked to morphological alterations of the neuromuscular presynaptic terminals, high turnover rate of acetylcholine receptor, and NMJ dismantlement. The analysis of potential molecular mechanisms that mediate the toxic activity of SOD1 G93A revealed a causal link between protein kinase Cθ (PKCθ) activation and NMJ disintegration. The study discloses the molecular mechanism that triggers functional denervation associated with the toxic activity of muscle SOD1 G93A expression and suggests the possibility of developing a new strategy to counteract age- and pathology-associated denervation based on pharmacological inhibition of PKCθ activity. Collectively, these data indicate that muscle-specific accumulation of oxidative damage can affect neuromuscular communication and induce NMJ dismantlement through a PKCθ-dependent mechanism. Antioxid. Redox Signal. 28, 1105-1119.

Operant conditioning of the soleus H-reflex does not induce long-term changes in the gastrocnemius H-reflexes and does not disturb normal locomotion in humans.

Science.gov (United States)

Makihara, Yukiko; Segal, Richard L; Wolpaw, Jonathan R; Thompson, Aiko K

2014-09-15

In normal animals, operant conditioning of the spinal stretch reflex or the H-reflex has lesser effects on synergist muscle reflexes. In rats and people with incomplete spinal cord injury (SCI), soleus H-reflex operant conditioning can improve locomotion. We studied in normal humans the impact of soleus H-reflex down-conditioning on medial (MG) and lateral gastrocnemius (LG) H-reflexes and on locomotion. Subjects completed 6 baseline and 30 conditioning sessions. During conditioning trials, the subject was encouraged to decrease soleus H-reflex size with the aid of visual feedback. Every sixth session, MG and LG H-reflexes were measured. Locomotion was assessed before and after conditioning. In successfully conditioned subjects, the soleus H-reflex decreased 27.2%. This was the sum of within-session (task dependent) adaptation (13.2%) and across-session (long term) change (14%). The MG H-reflex decreased 14.5%, due mainly to task-dependent adaptation (13.4%). The LG H-reflex showed no task-dependent adaptation or long-term change. No consistent changes were detected across subjects in locomotor H-reflexes, EMG activity, joint angles, or step symmetry. Thus, in normal humans, soleus H-reflex down-conditioning does not induce long-term changes in MG/LG H-reflexes and does not change locomotion. In these subjects, task-dependent adaptation of the soleus H-reflex is greater than it is in people with SCI, whereas long-term change is less. This difference from results in people with SCI is consistent with the fact that long-term change is beneficial in people with SCI, since it improves locomotion. In contrast, in normal subjects, long-term change is not beneficial and may necessitate compensatory plasticity to preserve satisfactory locomotion. Copyright © 2014 the American Physiological Society.

Immobilization/remobilization and the regulation of muscle mass

Science.gov (United States)

Almon, R. R.

1983-01-01

The relationship between animal body weight and the wet and dry weights of the soleus and EDL muscles was derived. Procedures were examined for tissue homogenization, fractionation, protein determination and DNA determination. A sequence of procedures and buffers were developed to carry out all analyses on one small muscle. This would yield a considerable increase in analytical strength associated with paired statistics. The proposed casting procedure which was to be used for immobilization was reexamined.

Proteome-wide muscle protein fractional synthesis rates predict muscle mass gain in response to a selective androgen receptor modulator in rats.

Science.gov (United States)

Shankaran, Mahalakshmi; Shearer, Todd W; Stimpson, Stephen A; Turner, Scott M; King, Chelsea; Wong, Po-Yin Anne; Shen, Ying; Turnbull, Philip S; Kramer, Fritz; Clifton, Lisa; Russell, Alan; Hellerstein, Marc K; Evans, William J

2016-03-15

Biomarkers of muscle protein synthesis rate could provide early data demonstrating anabolic efficacy for treating muscle-wasting conditions. Androgenic therapies have been shown to increase muscle mass primarily by increasing the rate of muscle protein synthesis. We hypothesized that the synthesis rate of large numbers of individual muscle proteins could serve as early response biomarkers and potentially treatment-specific signaling for predicting the effect of anabolic treatments on muscle mass. Utilizing selective androgen receptor modulator (SARM) treatment in the ovariectomized (OVX) rat, we applied an unbiased, dynamic proteomics approach to measure the fractional synthesis rates (FSR) of 167-201 individual skeletal muscle proteins in triceps, EDL, and soleus. OVX rats treated with a SARM molecule (GSK212A at 0.1, 0.3, or 1 mg/kg) for 10 or 28 days showed significant, dose-related increases in body weight, lean body mass, and individual triceps but not EDL or soleus weights. Thirty-four out of the 94 proteins measured from the triceps of all rats exhibited a significant, dose-related increase in FSR after 10 days of SARM treatment. For several cytoplasmic proteins, including carbonic anhydrase 3, creatine kinase M-type (CK-M), pyruvate kinase, and aldolase-A, a change in 10-day FSR was strongly correlated (r(2) = 0.90-0.99) to the 28-day change in lean body mass and triceps weight gains, suggesting a noninvasive measurement of SARM effects. In summary, FSR of multiple muscle proteins measured by dynamics of moderate- to high-abundance proteins provides early biomarkers of the anabolic response of skeletal muscle to SARM. Copyright © 2016 the American Physiological Society.

Next generation renal denervation: chemical “perivascular” renal denervation with alcohol using a novel drug infusion catheter

Energy Technology Data Exchange (ETDEWEB)

Fischell, Tim A. [Borgess Heart Institute, 1521 Gull Road, Kalamazoo, MI, 49008 (United States); Ablative Solutions, 801 Hermosa Way, Menlo Park, CA, 94025 (United States); Fischell, David R.; Ghazarossian, Vartan E. [Ablative Solutions, 801 Hermosa Way, Menlo Park, CA, 94025 (United States); Vega, Félix [Preclinical Consultation, San Francisco, CA (United States); Ebner, Adrian [Clinics, Ascension (Paraguay)

2015-06-15

Background/Purpose: We update the pre-clinical and early clinical results using a novel endovascular approach, to perform chemical renal denervation, via peri-adventitial injection of micro-doses of dehydrated alcohol (ethanol–EtOH). Methods/Materials: A novel, three-needle delivery device (Peregrine™) was used to denervate the renal arteries of adult swine (n = 17) and in a first-in-man feasibility study (n = 18). In the pre-clinical testing EtOH was infused bilaterally with one infusion per renal artery into to the perivascular space, using EtOH doses of 0.3 ml/artery (n = 8), and 0.6 ml/artery (n = 9), and with saline sham control (0.4 ml/artery n = 3). Renal parenchymal norepinephrine (NE) concentration (performed blindly), and safety were the primary endpoints. Data from the first-in-man study (n = 18) to evaluate device performance, safety and peri-procedural pain are reported. Results: In the pre-clinical testing renal function was unchanged at 3-month follow-up. Angiography at 90 days (n = 34 arteries) demonstrated normal appearing renal arteries, unchanged from baseline, and without stenosis or other abnormalities. The reductions in mean renal parenchymal NE reductions at 3 months were 68% and 88% at doses of 0.3 and 0.6 ml, respectively (p < 0.001 vs. controls). In the first-in-man study, there was 100% device success, no complications, a mean treatment time of 4.3 ± 3 minutes/artery, and minimal or no patient discomfort during treatment. Angiography at 6-months showed no evidence of renal artery stenosis, and evidence of a reduction of blood pressure from baseline. Conclusion: Perivascular RDN using micro-doses of alcohol is a promising alternative to energy-based systems to achieve dose-dependent, predictable, safe and essentially painless renal denervation. Further clinical evaluation is warranted. Summary: (For annotated table of contents) This paper describes the preclinical results, in a porcine model, and the early first-in-man results, using

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.

Systems analysis of transcriptional data provides insights into muscle's biological response to botulinum toxin.

Science.gov (United States)

Mukund, Kavitha; Mathewson, Margie; Minamoto, Viviane; Ward, Samuel R; Subramaniam, Shankar; Lieber, Richard L

2014-11-01

This study provides global transcriptomic profiling and analysis of botulinum toxin A (BoNT-A)-treated muscle over a 1-year period. Microarray analysis was performed on rat tibialis anterior muscles from 4 groups (n = 4/group) at 1, 4, 12, and 52 weeks after BoNT-A injection compared with saline-injected rats at 12 weeks. Dramatic transcriptional adaptation occurred at 1 week with a paradoxical increase in expression of slow and immature isoforms, activation of genes in competing pathways of repair and atrophy, impaired mitochondrial biogenesis, and increased metal ion imbalance. Adaptations of the basal lamina and fibrillar extracellular matrix (ECM) occurred by 4 weeks. The muscle transcriptome returned to its unperturbed state 12 weeks after injection. Acute transcriptional adaptations resemble denervated muscle with some subtle differences, but resolved more quickly compared with denervation. Overall, gene expression across time correlates with the generally accepted BoNT-A time course and suggests that the direct action of BoNT-A in skeletal muscle is relatively rapid. © 2014 Wiley Periodicals, Inc.

Immunohistochemical analysis of laryngeal muscles in normal horses and horses with subclinical recurrent laryngeal neuropathy.

Science.gov (United States)

Rhee, Hannah S; Steel, Catherine M; Derksen, Frederik J; Robinson, N Edward; Hoh, Joseph F Y

2009-08-01

We used immunohistochemistry to examine myosin heavy-chain (MyHC)-based fiber-type profiles of the right and left cricoarytenoideus dorsalis (CAD) and arytenoideus transversus (TrA) muscles of six horses without laryngoscopic evidence of recurrent laryngeal neuropathy (RLN). Results showed that CAD and TrA muscles have the same slow, 2a, and 2x fibers as equine limb muscles, but not the faster contracting fibers expressing extraocular and 2B MyHCs found in laryngeal muscles of small mammals. Muscles from three horses showed fiber-type grouping bilaterally in the TrA muscles, but only in the left CAD. Fiber-type grouping suggests that denervation and reinnervation of fibers had occurred, and that these horses had subclinical RLN. There was a virtual elimination of 2x fibers in these muscles, accompanied by a significant increase in the percentage of 2a and slow fibers, and hypertrophy of these fiber types. The results suggest that multiple pathophysiological mechanisms are at work in early RLN, including selective denervation and reinnervation of 2x muscle fibers, corruption of neural impulse traffic that regulates 2x and slow muscle fiber types, and compensatory hypertrophy of remaining fibers. We conclude that horses afflicted with mild RLN are able to remain subclinical by compensatory hypertrophy of surviving muscle fibers.

Double gene deletion reveals the lack of cooperation between PPARα and PPARβ in skeletal muscle

International Nuclear Information System (INIS)

Bedu, E.; Desplanches, D.; Pequignot, J.; Bordier, B.; Desvergne, B.

2007-01-01

The peroxisome proliferator-activated receptors (PPARs) are involved in the regulation of most of the pathways linked to lipid metabolism. PPARα and PPARβ isotypes are known to regulate muscle fatty acid oxidation and a reciprocal compensation of their function has been proposed. Herein, we investigated muscle contractile and metabolic phenotypes in PPARα-/-, PPARβ-/-, and double PPARα-/- β-/- mice. Heart and soleus muscle analyses show that the deletion of PPARα induces a decrease of the HAD activity (β-oxidation) while soleus contractile phenotype remains unchanged. A PPARβ deletion alone has no effect. However, these mild phenotypes are not due to a reciprocal compensation of PPARβ and PPARα functions since double gene deletion PPARα-PPARβ mostly reproduces the null PPARα-mediated reduced β-oxidation, in addition to a shift from fast to slow fibers. In conclusion, PPARβ is not required for maintaining skeletal muscle metabolic activity and does not compensate the lack of PPARα in PPARα null mice

Changes in FDB and soleus muscle activity after a train of stimuli during upright stance Alterações pós-trem de estímulo, na atividade dos músculos FDB e sóleus durante a postura ortostática

Directory of Open Access Journals (Sweden)

Liria A. Okai

2012-06-01

Full Text Available BACKGROUND: Evidence of self-sustained muscle activation following a brief electrical stimulation has been reported in the literature for certain muscles. OBJECTIVES: This report shows that the foot muscle (Flexor Digitorum Brevis - FDB shows a self-sustained increase in muscle activity during upright stance in some subjects following a train of stimuli to the tibial nerve. METHODS: Healthy subjects were requested to stand upright and surface EMG electrodes were placed on the FDB, Soleus and Tibialis Anterior muscles. After background muscle activity (BGA acquisition, a 50 Hz train of stimuli was applied to the tibial nerve at the popliteal fossa. The root mean square values (RMS of the BGA and the post-stimulus muscle activation were computed. RESULTS: There was a 13.8% average increase in the FDB muscle EMG amplitude with respect to BGA after the stimulation was turned off. The corresponding post-stimulus Soleus EMG activity decreased by an average of 9.2%. We hypothesize that the sustained contraction observed in the FDB following stimulus may be evidence of persistent inward currents (PIC generated in FDB spinal motoneurons. The post-stimulus decrease in soleus activity may have occurred due to the action of inhibitory interneurons caused by the PICs, which were triggered by the stimulus train. CONCLUSIONS: These sustained post-stimulation changes in postural muscle activity, found in different levels in different subjects, may be part of a set of possible responses that contribute to overall postural control.CONTEXTUALIZAÇÃO: Existem evidências de ativação autossustentada em certos músculos pós-estimulação elétrica. OBJETIVOS: Mostrar que, em alguns sujeitos, o músculo do pé (Flexor Digitorum Brevis - FDB também pode apresentar aumento de atividade autossustentada na posição ortostática pós-trem de estímulo no nervo tibial. MÉTODOS: Sujeitos foram solicitados a permanecer na posição ortostática e sinais eletromiogr

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

Metabolism of branched-chain amino acids in leg muscles from tail-cast suspended intact and adrenalectomized rats

Science.gov (United States)

Jaspers, Stephen R.; Henriksen, Erik; Jacob, Stephan; Tischler, Marc E.

1989-01-01

The effects of muscle unloading, adrenalectomy, and cortisol treatment on the metabolism of branched-chain amino acids in the soleus and extensor digitorum longus of tail-cast suspended rats were investigated using C-14-labeled lucine, isoleucine, and valine in incubation studies. It was found that, compared to not suspended controls, the degradation of branched-chain amino acids in hind limb muscles was accelerated in tail-cast suspended rats. Adrenalectomy was found to abolish the aminotransferase flux and to diminish the dehydrogenase flux in the soleus. The data also suggest that cortisol treatment increases the rate of metabolism of branched-chain amino acids at the dehydrogenase step.

Thyroid Hormone Signaling in Male Mouse Skeletal Muscle Is Largely Independent of D2 in Myocytes